39 results on '"Pattij T"'
Search Results
2. The CADM2 gene and behavior: A phenome-wide scan in UK-Biobank
- Author
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Pasman, J.A., Chen, Z., Smit, D.J.A., Vink, J.M., Oever, M.C. van den, Pattij, T., Vries, T.J. de, Abdellaoui, A., Verweij, K.J.H., Pasman, J.A., Chen, Z., Smit, D.J.A., Vink, J.M., Oever, M.C. van den, Pattij, T., Vries, T.J. de, Abdellaoui, A., and Verweij, K.J.H.
- Abstract
Item does not contain fulltext, The cell adhesion molecule 2 (CADM2) gene has appeared among the top associations in a wide range of genome-wide association studies (GWASs). This study aims to: (1) examine how widespread the role of CADM2 is in behavioural traits, and (2) investigate trait-specific effects on CADM2 expression levels across tissues. We conducted a phenome-wide association study in UK Biobank (N = 12,211–453,349) on 242 psycho-behavioral traits, both at the SNP and the gene-level. For comparison, we repeated the analyses for other large (and high LD) genes. We found significant associations between CADM2 and 50 traits (including cognitive, risk taking, and dietary traits), many more than for the comparison genes. We show that many trait associations are reduced when taking geographical stratification into account. S-Predixcan revealed that CADM2 expression in brain tissues was significantly associated with many traits; highly significant effects were also observed for lung, mammary, and adipose tissues. In conclusion, this study shows that the role of CADM2 extends to a wide range of psycho-behavioral traits, suggesting these traits may share a common biological denominator.
- Published
- 2022
3. Antidepressants, Sexual Behavior, and Translational Models for Male Sexual Dysfunction:Development of Animal Models, Pharmacology, and Genetics
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Olivier, J., Janssen, Josien, Pattij, T., De Prêtre, Stephen, Olivier, Berend, Kim, Y.K., Amidfar, M., Olivier lab, Anatomy and neurosciences, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
- Subjects
sexual behavior ,animal model ,male sexual dysfunction ,Antidepressant - Abstract
The discovery and development of the first generations of antidepressants in the last century, the tricyclic antidepressants and serotonin reuptake blockers, were a breakthrough in the pharmacological treatment of major depression. Along with the antidepressant activity came the sexual side effects, which contributed considerably to the high level of stopping treatment. In the subsequent search for new and better antidepressants, early detection of potential sexual side effects is of paramount importance, hence the need for predictive animal models. Sexual behavior of the male rat has been frequently used to detect inhibiting effects of psychotropic drugs. We developed a male rat model of sexual behavior that mirrored the human profile of antidepressants: sexual inhibitory effects only after chronic but not after acute administration. We extensively describe the methodology and the model and show the profile of various antidepressants and other psychotropics in male rat sexual behavior. To generate male rats for our experiments, we employ large cohorts of male Wistar rats that are trained once weekly in 30-min tests with estrous females for at least 4–7 times. During this training each individual rat develops its own stable sexual phenotype, being between 0 and 5 ejaculations per 30-min test. Such a (endo)phenotype appears very stable over time and animals can be used repeatedly for pharmacological experiments for over a year, providing an ideal intra-male experimental model. For testing the effects of drugs (e.g., antidepressants) on sexual behavior, we standardly use rats with stable ejaculation numbers of 2–3 per test, providing a model that is sensitive to both sexual-stimulating (prosexual) and sexual-inhibiting effects, and are able to dissect acute and chronic effects of drugs. The effects of various drugs tested in this model over the last decades are given. By using the large cohort approach and sexual training, we discovered that the number of rats with 0, 1, 2, 3, 4, or 5 ejaculations (E) per test shows a bell-shaped distribution. Relatively few rats have either 0 or 1 E or 4 or 5 E/test, whereas those with 2 or 3 E/test are much more abundant. Based on the similarity of rat ejaculation number distribution with that of ejaculation latency distribution in human males, we postulate that fast ejaculating rats (4 or 5 E/test) are a translational model for premature ejaculation, whereas slow or not ejaculating rats (0 or 1 E/test) could model an-ejaculation or delayed ejaculation in men. Several pharmacological experiments are described supporting the use of these translational endophenotypic models of normal, slow, and fast ejaculating rats. The importance of the serotonergic system and in particular the role of 5-HT1A receptors in male sexual behavior is highlighted. The serotonin transporter knockout rat illustrates the influence of genetic modifications in male rat sexual behavior. This model displays a comparable sexual phenotype as chronically SSRI-treated rats. Such a genetic model may be useful in detecting underlying mechanisms of sexual dysfunctions (like delayed ejaculation) but may also contribute to the study of critically involved neurochemical systems. Finally, testing drugs with multimodal mechanisms of action in such genetic models might unravel new mechanisms involved, finally contributing to better treatments.
- Published
- 2022
4. The CADM2 gene and behavior: A phenome-wide scan in UK-Biobank
- Author
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Karin J. H. Verweij, Jacqueline M. Vink, Abdel Abdellaoui, Joëlle A. Pasman, van den Oever Mc, Pattij T, de Vries Tj, and Chen Z
- Subjects
Genetics ,SNP ,Common denominator ,Biology ,Health behavior ,Substance use ,Phenome ,Biobank ,Gene - Abstract
This phenome-wide association study examined SNP and gene–based associations of the CADM2 gene with 242 psycho-behavioral traits (N=12,211–453,349). We found significant associations with 51 traits, many more than for other genes. We replicated previously reported associations with substance use, risk-taking, and health behavior, and uncovered novel associations with sleep and dietary traits. Accordingly, CADM2 is involved in many psycho-behavioral traits, suggesting a common denominator in their biology.
- Published
- 2021
5. Neural substrates of impulsive decision making modulated by modafinil in alcohol-dependent patients
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Schmaal, L., Goudriaan, A. E., Joos, L., Dom, G., Pattij, T., van den Brink, W., and Veltman, D. J.
- Published
- 2014
6. Subchronic administration of atomoxetine causes an enduring reduction in context-induced relapse to cocaine seeking without affecting impulsive decision making
- Author
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Broos, N., Loonstra, R., van Mourik, Y., Schetters, D., Schoffelmeer, A.N.M., Pattij, T., de Vries, T.J., Molecular and Cellular Neurobiology, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, Anatomy and neurosciences, and NCA - Neurobiology of mental health
- Subjects
SDG 16 - Peace ,SDG 16 - Peace, Justice and Strong Institutions ,Justice and Strong Institutions - Abstract
Previous work has established a robust relationship between impulsivity and addiction, and revealed that impulsive decision making predisposes the vulnerability to cocaine-seeking behavior in rats. An important next step is to assess whether elevated relapse vulnerability can be treated via the reduction of impulsive decision making. Therefore, this study explored whether subchronic atomoxetine treatment can reduce relapse vulnerability by reducing impulsive decision making. Rats were trained in the delayed reward task and were subjected to 3 weeks of cocaine self-administration. Following drug self-administration, animals were divided to different experimental groups and received the noradrenaline transporter inhibitor and attention-deficit/hyperactivity disorder drug atomoxetine or vehicle subchronically for 20 days. On days1 and 10 after treatment cessation, a context-induced reinstatement test was performed. Throughout the entire experiment, changes in impulsive decision making were continuously monitored. Subchronic treatment with atomoxetine reduced context-induced reinstatement both 1 and 10 days after treatment cessation, only in animals receiving no extinction training. Interestingly, neither subchronic nor acute atomoxetine treatments affected impulsive decision making. Our data indicate that the enduring reduction in relapse sensitivity by atomoxetine occured independent of a reduction in impulsive decision making. Nonetheless, repeated atomoxetine administration seems a promising pharmacotherapeutical strategy to prevent relapse to cocaine seeking in abstinent drug-dependent subjects.
- Published
- 2015
7. Increased impulsivity in rats as a result of repeated cycles of alcohol intoxication and abstinence
- Author
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Irimia, C., Wiskerke, J., Natividad, L.A., Polis, I.Y., de Vries, T.J., Pattij, T., Parsons, L.H., Anatomy and neurosciences, NCA - Neurobiology of mental health, Molecular and Cellular Neurobiology, and Neuroscience Campus Amsterdam - Neurobiology of Mental Health
- Subjects
SDG 3 - Good Health and Well-being - Abstract
Impulsivity is a risk factor for alcoholism, and long-term alcohol exposure may further impair impulse control in a manner that propels problematic alcohol use. The present study employed the rat 5-choice serial reaction time task (5-CSRTT) to measure behavioral inhibition and attentional capacity during abstinence from repeated 5-day cycles of alcohol liquid diet consumption. Task performance was not disrupted following the first cycle of alcohol exposure; however, evidence of impaired behavioral inhibition emerged following the third cycle of alcohol exposure. In comparison with controls, alcoholic rats exhibited deficits in inhibitory control during cognitively challenging 5-CSRTT tests employing variable intertrial interval (varITI). This behavioral disruption was not present during early abstinence (3 days) but was evident by 7 days of abstinence and persisted for at least 34 days. Interestingly, renewed alcohol consumption ameliorated these disruptions in impulse control, although deficient behavioral inhibition re-emerged during subsequent abstinence. Indices of increased impulsivity were no longer present in tests conducted after 49 days of abstinence. Alcohol-related impairments in impulse control were not evident in sessions employing highly familiar task parameters regardless of the abstinence period, and control experiments confirmed that performance deficits during the challenge sessions were unlikely to result from alcohol-related disruption in the adaptation to repeated varITI testing. Together, the current findings demonstrate that chronic intermittent alcohol consumption results in decreased behavioral inhibition in rats that is temporally similar to clinical observations of disrupted impulsive control in abstinent alcoholics performing tasks of behavioral inhibition. The present study employed the 5-Choice Serial Reaction Time Task (5-CSRTT) to evaluate the effects of prior chronic alcohol exposure on the impulsive-like behavior in rats. Alcohol-exposed rats exhibited deficits in inhibitory control and increased perseverative behavior during 5-CSRTT tests employing variable inter-trial intervals. These disruptions were not present during early abstinence (3d) but emerged by 7d abstinence and persisted for at least 34d. Renewed alcohol consumption ameliorated these disruptions, though deficient behavioral inhibition re-emerged during subsequent abstinence.
- Published
- 2015
8. DISRUPTING THE RECONSOLIDATION OF ALCOHOL-RELATED MEMORIES THROUGH WORKING MEMORY INTERFERENCE IN HAZARDOUS DRINKERS
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Kaag, A. M., Wiers, R., de Vries, T. J., Goudriaan, A., Pattij, T., Willuh, I., Anatomy and neurosciences, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
- Published
- 2017
9. A high working memory load preceding alcohol cue exposure, reduces the desire for alcohol in non-treatment seeking problem drinkers
- Author
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Kaag, A.M., primary, Pattij, T., additional, De Vries, T.J., additional, Goudriaan, A.E., additional, and Wiers, R.W., additional
- Published
- 2017
- Full Text
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10. The cannabinoid system and impulsive behavior
- Author
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Wiskerke, J, Pattij, T, Fattore, Liana, Anatomy and neurosciences, and Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention
- Published
- 2015
11. P.6.b.012 - A high working memory load preceding alcohol cue exposure, reduces the desire for alcohol in non-treatment seeking problem drinkers
- Author
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Kaag, A.M., Pattij, T., De Vries, T.J., Goudriaan, A.E., and Wiers, R.W.
- Published
- 2017
- Full Text
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12. Cortical contributions to cognitive control
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Bruinsma, B., Mansvelder, HD, Pattij, T., Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, and Integrative Neurophysiology
- Published
- 2020
13. Is impulsivity a treatable risk factor of cocaine addiction?
- Author
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Broos-Boersma, N, de Vries, TJ, Pattij, T., de Vries, Taco, Pattij, Tommy, and Anatomy and neurosciences
- Subjects
impulsive action ,impulsivity ,cocaïne addiction ,impulsive decision making ,cocaïne self-administration - Published
- 2018
14. Control your desire: Deep brain stimulation in impulse control and heroin use disorder: a translational approach
- Author
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Schippers, M.C., de Vries, Taco, Pattij, Tommy, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, de Vries, TJ, and Pattij, T.
- Subjects
impulsivity ,addiction ,heroin ,deep brain stimulation - Published
- 2017
15. Prefrontal Cortical to Mediodorsal Thalamus Projection Neurons Regulate Posterror Adaptive Control of Behavior.
- Author
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Bruinsma B, Pattij T, and Mansvelder HD
- Subjects
- Rats, Male, Animals, Neural Pathways physiology, Interneurons, Impulsive Behavior, Prefrontal Cortex physiology, Thalamus physiology
- Abstract
Adaptive control is the online adjustment of behavior to guide and optimize responses after errors or conflict. The neural circuits involved in monitoring and adapting behavioral performance following error are poorly understood. The prefrontal cortex (PFC) plays a critical role in this form of control. However, these brain areas are densely connected with many other regions, and it is unknown which projections are critical for adaptive behavior. Here, we tested the involvement of four distinct dorsal and ventral prefrontal cortical projections to striatal and thalamic target areas in adaptive control. We re-analyzed data from published experiments, using trial-by-trial analyses of behavior in an operant task for attention and impulsivity. We find that male rats slow their responses and perform worse following errors. Moreover, by combining retrograde labeling and chemogenetic silencing, we find that dorsomedial prefrontal pyramidal neurons that project to the lateral nucleus of the mediodorsal thalamus (MDL) are involved in posterror performance and timing of responses, specifically with unpredictable delays until stimulus presentation. Together, these data show that dorsal medial PFC (mPFC) projection neurons targeting the lateral MDT regulate adaptive control to flexibly optimize behavioral responses in goal-directed behavior., (Copyright © 2022 Bruinsma et al.)
- Published
- 2022
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16. The CADM2 Gene and Behavior: A Phenome-Wide Scan in UK-Biobank.
- Author
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Pasman JA, Chen Z, Smit DJA, Vink JM, Van Den Oever MC, Pattij T, De Vries TJ, Abdellaoui A, and Verweij KJH
- Subjects
- Biological Specimen Banks, Phenotype, United Kingdom, Genome-Wide Association Study, Polymorphism, Single Nucleotide genetics
- Abstract
The cell adhesion molecule 2 (CADM2) gene has appeared among the top associations in a wide range of genome-wide association studies (GWASs). This study aims to: (1) examine how widespread the role of CADM2 is in behavioural traits, and (2) investigate trait-specific effects on CADM2 expression levels across tissues. We conducted a phenome-wide association study in UK Biobank (N = 12,211-453,349) on 242 psycho-behavioral traits, both at the SNP and the gene-level. For comparison, we repeated the analyses for other large (and high LD) genes. We found significant associations between CADM2 and 50 traits (including cognitive, risk taking, and dietary traits), many more than for the comparison genes. We show that many trait associations are reduced when taking geographical stratification into account. S-Predixcan revealed that CADM2 expression in brain tissues was significantly associated with many traits; highly significant effects were also observed for lung, mammary, and adipose tissues. In conclusion, this study shows that the role of CADM2 extends to a wide range of psycho-behavioral traits, suggesting these traits may share a common biological denominator., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
17. Neural basis of operant behaviors maintained on the differential-reinforcement-of-low-rate (DRL) schedule in rodents.
- Author
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Liao RM and Pattij T
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- Animals, Dopamine, Reinforcement Schedule, Reinforcement, Psychology, Conditioning, Operant, Rodentia
- Abstract
Various schedules of reinforcement have long been used in experimental psychology to establish and maintain operant behaviors. These reinforcement contingencies have also been widely applied in preclinical psycho- and neurobiology research. However, the differential reinforcement of low-rate response (DRL) schedule has received less attention than other schedules based on response ratios or different types of intervals. Hence, little is known about the neural basis of DRL schedule-controlled behavior. Herein, we review early and recent reports of rodent experiments utilizing brain lesions and intracranial drug infusions to respectively elucidate the neural substrates and neuropharmacological basis of DRL behavior. Overall, the available evidence implies that 1) certain cortical and subcortical areas are differentially involved in the DRL behavior and 2) disruption of dopamine or serotonin neurotransmission alters DRL behavior. We further identify remaining challenges in the field and suggest future work that will be helpful for understanding the neurobehavioral mechanisms of the DRL schedule of reinforcement., (Copyright © 2022 Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
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18. Prenatal exposure to morphine impairs attention and impulsivity in adult rats.
- Author
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Alaee E, Moazen P, Pattij T, Semnanian S, and Azizi H
- Subjects
- Analgesics, Opioid, Animals, Attention, Female, Impulsive Behavior, Male, Pregnancy, Rats, Morphine, Prenatal Exposure Delayed Effects
- Abstract
Rationale: An alarming number of neonates born with prenatal exposure to morphine has resulted from the opioid epidemic; however, the long-term effects of prenatal opioid exposure on offspring behavior remain relatively unknown. In this study, we evaluated whether prenatal exposure to the mu opioid receptor agonist, morphine, has enduring effects on cognitive functions in adult life., Methods: On embryonic days 11-18 (E11-E18), female pregnant rats were injected subcutaneously with either morphine or saline twice daily. Adult male offspring that was prenatally exposed to saline or morphine was trained in the 5-choice serial reaction time test (5-CSRTT) to test their cognitive abilities under baseline conditions. Next, these rats were treated with saline (1 ml/kg), naloxone (1 mg/kg), and acute morphine (1, 3, 5 mg/kg), subcutaneously, once daily and following drug challenges rats were tested in the 5-CSRTT. Meanwhile, behavioral performance on training days between opioid drug challenges were analyzed to monitor possible drug-induced shifts in baseline performance. As a final experiment in order to investigate subchronic exposure to morphine, rats were injected with 5 mg/kg morphine for 5 days and then naloxone in the last day of the experiment (day 6)., Results: Firstly, during acquisition of a stable baseline in the training phase, rats prenatally exposed to morphine showed delayed learning of the task demands. Furthermore, under baseline responding the rats prenatally exposed to morphine showed declined inhibitory control demonstrated by increased impulsive and compulsive-like responding compared to rats prenatally exposed to saline. Moreover, acute and subchronic morphine challenges in the rats prenatally exposed to morphine caused a deficit in visuospatial attention in comparison with saline treatment as well as the rats prenatally exposed to saline. These effects were abolished by naloxone., Conclusion: The current findings indicate a direct causal effect of prenatal morphine exposure on inhibitory control and task learning later in life, as well as deficits in attention following morphine exposure in adulthood., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2021
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19. Where Dopaminergic and Cholinergic Systems Interact: A Gateway for Tuning Neurodegenerative Disorders.
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Amalric M, Pattij T, Sotiropoulos I, Silva JM, Sousa N, Ztaou S, Chiamulera C, Wahlberg LU, Emerich DF, and Paolone G
- Abstract
Historically, many investigations into neurodegenerative diseases have focused on alterations in specific neuronal populations such as, for example, the loss of midbrain dopaminergic neurons in Parkinson's disease (PD) and loss of cholinergic transmission in Alzheimer's disease (AD). However, it has become increasingly clear that mammalian brain activities, from executive and motor functioning to memory and emotional responses, are strictly regulated by the integrity of multiple interdependent neuronal circuits. Among subcortical structures, the dopaminergic nigrostriatal and mesolimbic pathways as well as cholinergic innervation from basal forebrain and brainstem, play pivotal roles in orchestrating cognitive and non-cognitive symptoms in PD and AD. Understanding the functional interactions of these circuits and the consequent neurological changes that occur during degeneration provides new opportunities to understand the fundamental inter-workings of the human brain as well as develop new potential treatments for patients with dysfunctional neuronal circuits. Here, excerpted from a session of the European Behavioral Pharmacology Society meeting (Braga, Portugal, August 2019), we provide an update on our recent work in behavioral and cellular neuroscience that primarily focuses on interactions between cholinergic and dopaminergic systems in PD models, as well as stress in AD. These brief discussions include descriptions of (1) striatal cholinergic interneurons (CINs) and PD, (2) dopaminergic and cholinergic modulation of impulse control, and (3) the use of an implantable cell-based system for drug delivery directly the into brain and (4) the mechanisms through which day life stress, a risk factor for AD, damage protein and RNA homeostasis leading to AD neuronal malfunction., Competing Interests: LW is the CEO of Gloriana Therapeutics, Inc., a for-profit biotechnology company that is developing the encapsulated cell technology to treat CNS diseases. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Amalric, Pattij, Sotiropoulos, Silva, Sousa, Ztaou, Chiamulera, Wahlberg, Emerich and Paolone.)
- Published
- 2021
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20. Bi-directional regulation of cognitive control by distinct prefrontal cortical output neurons to thalamus and striatum.
- Author
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de Kloet SF, Bruinsma B, Terra H, Heistek TS, Passchier EMJ, van den Berg AR, Luchicchi A, Min R, Pattij T, and Mansvelder HD
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- Animals, Corpus Striatum cytology, Electrophysiological Phenomena, Male, Models, Neurological, Neural Pathways physiology, Prefrontal Cortex cytology, Rats, Long-Evans, Thalamus cytology, Rats, Cognition physiology, Corpus Striatum physiology, Neurons physiology, Prefrontal Cortex physiology, Thalamus physiology
- Abstract
The medial prefrontal cortex (mPFC) steers goal-directed actions and withholds inappropriate behavior. Dorsal and ventral mPFC (dmPFC/vmPFC) circuits have distinct roles in cognitive control, but underlying mechanisms are poorly understood. Here we use neuroanatomical tracing techniques, in vitro electrophysiology, chemogenetics and fiber photometry in rats engaged in a 5-choice serial reaction time task to characterize dmPFC and vmPFC outputs to distinct thalamic and striatal subdomains. We identify four spatially segregated projection neuron populations in the mPFC. Using fiber photometry we show that these projections distinctly encode behavior. Postsynaptic striatal and thalamic neurons differentially process synaptic inputs from dmPFC and vmPFC, highlighting mechanisms that potentially amplify distinct pathways underlying cognitive control of behavior. Chemogenetic silencing of dmPFC and vmPFC projections to lateral and medial mediodorsal thalamus subregions oppositely regulate cognitive control. In addition, dmPFC neurons projecting to striatum and thalamus divergently regulate cognitive control. Collectively, we show that mPFC output pathways targeting anatomically and functionally distinct striatal and thalamic subregions encode bi-directional command of cognitive control.
- Published
- 2021
- Full Text
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21. Tracing goes viral: Viruses that introduce expression of fluorescent proteins in chemically-specific neurons.
- Author
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Luchicchi A, Pattij T, Viaña JNM, de Kloet S, and Marchant N
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- Animals, Dogs, Genetic Vectors, Neurons, Optogenetics, Dependovirus genetics, Viruses genetics
- Abstract
Over the last century, there has been great progress in understanding how the brain works. In particular, the last two decades have been crucial in gaining more awareness over the complex functioning of neurotransmitter systems. The use of viral vectors in neuroscience has been pivotal for such development. Exploiting the properties of viral particles, modifying them according to the research needs, and making them target chemically-specific neurons, techniques such as optogenetics and chemogenetics have been developed, which could lead to a giant step toward gene therapy for brain disorders. In this review, we aim to provide an overview of some of the most widely used viral techniques in neuroscience. We will discuss advantages and disadvantages of these methods. In particular, attention is dedicated to the pivotal role played by the introduction of adeno-associated virus and the retrograde tracer canine-associated-2 Cre virus in order to achieve optimal visualization, and interrogation, of chemically-specific neuronal populations and their projections., (Copyright © 2020. Published by Elsevier B.V.)
- Published
- 2021
- Full Text
- View/download PDF
22. Prefrontal Cortical Projection Neurons Targeting Dorsomedial Striatum Control Behavioral Inhibition.
- Author
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Terra H, Bruinsma B, de Kloet SF, van der Roest M, Pattij T, and Mansvelder HD
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- Action Potentials physiology, Animals, Behavior, Animal, Corpus Striatum cytology, Male, Models, Animal, Neural Pathways physiology, Optogenetics, Prefrontal Cortex cytology, Rats, Stereotaxic Techniques, Synaptic Transmission physiology, Cognition physiology, Corpus Striatum physiology, Inhibition, Psychological, Neurons physiology, Prefrontal Cortex physiology
- Abstract
A neural pathway from prefrontal cortex (PFC) to dorsal striatum (DS) has been suggested to mediate cognitive control of behavior, including proactive inhibitory control and attention. However, a direct causal demonstration thereof is lacking. Here, we show that selective chemogenetic silencing of corticostriatal PFC neurons in rats increases premature responses. Wireless single-unit electrophysiological recordings of optogenetically identified corticostriatal PFC neurons revealed that the majority of these neurons encode behavioral trial outcome with persistent changes in firing rate. Attentional parameters were not affected by silencing corticostriatal PFC neurons, suggesting that these projection neurons encode a specific subset of cognitive behaviors. Compared to the general non-identified neuronal population in the PFC, frontostriatal neurons showed selective engagement during periods of inhibitory control. Our results demonstrate a role for corticostriatal neurons in inhibitory control and possibly suggest that distinct domains of cognitive control over behavior are encoded by specific projection neuron populations., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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23. Personality driven alcohol and drug abuse: New mechanisms revealed.
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Skóra MN, Pattij T, Beroun A, Kogias G, Mielenz D, de Vries T, Radwanska K, and Müller CP
- Subjects
- Alcohol Drinking, Animals, Impulsive Behavior, Mice, Personality, Alcoholism, Substance-Related Disorders
- Abstract
While the majority of the regular consumers of alcohol controls their consumption well over life span and even takes instrumentalization benefits from it, a minority, but yet high total number of users develops an alcohol addiction. It has long been known that particular personality types are more addiction prone than others. Here we review recent progress in the understanding of neurobiological pathways that determine personality and facilitate drug abuse. Novel approaches to characterize personality traits leading to addiction proneness in social settings in mice are discussed. A common genetic and neurobiological base for the behavioural traits of sensation seeking or a depressed phenotype and escalating alcohol consumption are reviewed. Furthermore, recent progress on how social and cognitive factors, including impulsivity and decision making, act at brain level to make an individual more vulnerable to alcohol abuse, are discussed. Altogether, this review provides an update on brain mechanisms underlying a broad spectrum of personality traits that make an individual more prone to alcohol and drug abuse and addiction., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2020
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- View/download PDF
24. The role of impulsivity as predisposing behavioural trait in different aspects of alcohol self-administration in rats.
- Author
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Pattij T, van Mourik Y, Diergaarde L, and de Vries TJ
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- Alcohol Abstinence psychology, Alcohol Drinking trends, Animals, Conditioning, Operant physiology, Impulsive Behavior physiology, Male, Rats, Rats, Wistar, Self Administration, Alcohol Drinking psychology, Conditioning, Operant drug effects, Ethanol administration & dosage, Impulsive Behavior drug effects
- Abstract
Background: Therapeutic interventions to promote abstinence and prevent relapse in alcohol use disorder (AUD) are limitedly available. Therefore, targeting risk factors in the onset and maintenance of AUD could pose an interesting alternative treatment strategy. In this regard, over the last decade trait impulsivity has received considerable attention as such a risk factor predisposing substance dependence both in clinical populations and preclinical rodent studies. This study investigated whether different forms of impulsivity (action versus choice) predict distinct stages of instrumental alcohol self-administration, extinction and cue-induced relapse., Methods: Two cohorts of n = 48 rats each were trained in an operant tasks for either impulsive action or impulsive choice. Subsequently, high and low impulsive rats were then tested in an alcohol self-administration and relapse model and following this retested in the impulsivity tasks to evaluate possible changes in impulsivity levels., Results: The current data show that neither impulsive action, nor impulsive choice predict the extent to which rats consume alcohol and the extent to which rats are motivated to self-administer alcohol. Moreover, extinction of responding for alcohol and cue-induced relapse was not predicted by impulsivity. Interestingly, rats and most prominently low impulsive rats became more impulsive after the alcohol self-administration procedure. Although due to employed experimental design it is not clear whether this resulted from alcohol consumption or alcohol abstinence., Conclusion: Together, these findings lend further support for the notion of a unidirectional relationship between self-administration of the depressant drug alcohol and impulsivity., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2020
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25. Author Correction: Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.
- Author
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Obermayer J, Luchicchi A, Heistek TS, de Kloet SF, Terra H, Bruinsma B, Mnie-Filali O, Kortleven C, Galakhova AA, Khalil AJ, Kroon T, Jonker AJ, de Haan R, van de Berg WDJ, Goriounova NA, de Kock CPJ, Pattij T, and Mansvelder HD
- Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
- Published
- 2020
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26. The Neuropharmacology of Impulsive Behaviour, an Update.
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Pattij T and Vanderschuren LJMJ
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- Dopamine, Impulsive Behavior, Norepinephrine, Optogenetics, Neuropharmacology
- Abstract
Neuropharmacological interventions in preclinical translational models of impulsivity have tremendously contributed to a better understanding of the neurochemistry and neural basis of impulsive behaviour. In this regard, much progress has been made over the last years, also due to the introduction of novel techniques in behavioural neuroscience such as optogenetics and chemogenetics. In this chapter, we will provide an update of how the behavioural pharmacology field has progressed and built upon existing data since an earlier review we wrote in 2008. To this aim, we will first give a brief background on preclinical translational models of impulsivity. Next, recent interesting evidence of monoaminergic modulation of impulsivity will be highlighted with a focus on the neurotransmitters dopamine and noradrenaline. Finally, we will close the chapter by discussing some novel directions and drug leads in the neuropharmacological modulation of impulsivity.
- Published
- 2020
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27. Prefrontal cortical ChAT-VIP interneurons provide local excitation by cholinergic synaptic transmission and control attention.
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Obermayer J, Luchicchi A, Heistek TS, de Kloet SF, Terra H, Bruinsma B, Mnie-Filali O, Kortleven C, Galakhova AA, Khalil AJ, Kroon T, Jonker AJ, de Haan R, van de Berg WDJ, Goriounova NA, de Kock CPJ, Pattij T, and Mansvelder HD
- Subjects
- Acetylcholine pharmacology, Animals, Attention physiology, Cerebral Cortex cytology, Cerebral Cortex metabolism, Choline O-Acetyltransferase metabolism, Female, Interneurons drug effects, Interneurons metabolism, Male, Mice, 129 Strain, Neurons drug effects, Neurons metabolism, Neurons physiology, Prefrontal Cortex cytology, Rats, Synaptic Transmission drug effects, Synaptic Transmission physiology, Vasoactive Intestinal Peptide metabolism, Attention drug effects, Cholinergic Agents pharmacology, Interneurons physiology, Prefrontal Cortex metabolism
- Abstract
Neocortical choline acetyltransferase (ChAT)-expressing interneurons are a subclass of vasoactive intestinal peptide (ChAT-VIP) neurons of which circuit and behavioural function are unknown. Here, we show that ChAT-VIP neurons directly excite neighbouring neurons in several layers through fast synaptic transmission of acetylcholine (ACh) in rodent medial prefrontal cortex (mPFC). Both interneurons in layers (L)1-3 as well as pyramidal neurons in L2/3 and L6 receive direct inputs from ChAT-VIP neurons mediated by fast cholinergic transmission. A fraction (10-20%) of postsynaptic neurons that received cholinergic input from ChAT-VIP interneurons also received GABAergic input from these neurons. In contrast to regular VIP interneurons, ChAT-VIP neurons did not disinhibit pyramidal neurons. Finally, we show that activity of these neurons is relevant for behaviour and they control attention behaviour distinctly from basal forebrain ACh inputs. Thus, ChAT-VIP neurons are a local source of cortical ACh that directly excite neurons throughout cortical layers and contribute to attention.
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- 2019
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28. Striatal alcohol cue-reactivity is stronger in male than female problem drinkers.
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Kaag AM, Wiers RW, de Vries TJ, Pattij T, and Goudriaan AE
- Subjects
- Adult, Alcoholism epidemiology, Female, Humans, Male, Netherlands epidemiology, Young Adult, Alcoholism diagnostic imaging, Alcoholism psychology, Craving physiology, Cues, Photic Stimulation methods, Sex Characteristics, Ventral Striatum diagnostic imaging
- Abstract
Despite apparent sex differences in the development and treatment of alcohol use disorder, relatively little is known about the underlying neural mechanisms. In this study, we therefore investigated neural cue-reactivity in a sample of male (n = 28) and female (n = 27) problem drinkers (matched on age and alcohol use severity) with an average alcohol use disorder identification test score of 12 which is indicative of a likely alcohol use disorder. Neural cue-reactivity data were extracted from four regions of interest: the ventral and dorsal striatum and the ventral and dorsal anterior cingulate cortex, with a significance level set at p < 0.05. While the cue-reactivity paradigm induced similar levels of self-reported craving in men and women, visual alcohol cues induced significantly stronger striatal activation in men compared to drinkers. While sex differences in ventral striatal cue-reactivity were partly explained by sex differences in alcohol intake, cannabis use, negative affect and anxiety, this was not the case for sex differences in dorsal striatal cue-reactivity. These results suggest that alcohol cues are differentially processed by men and women and that the neurobiological mechanisms behind cue-reactivity differ between the sexes. Consequently, paradigms using alcohol-related pictures may not be optimal to induce cue-reactivity in female drinkers and may not be optimal to measure neurobiological markers of alcohol use severity and relapse. Future alcohol cue-reactivity studies should, in addition to including both men and women, include different types of cues (e.g., stressors and imagery in addition to pictures) to assess sex differences in alcohol cue-reactivity., (© 2018 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
- Published
- 2019
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29. An automated home-cage-based 5-choice serial reaction time task for rapid assessment of attention and impulsivity in rats.
- Author
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Bruinsma B, Terra H, de Kloet SF, Luchicchi A, Timmerman AJ, Remmelink E, Loos M, Pattij T, and Mansvelder HD
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- Animals, Attention drug effects, Choice Behavior drug effects, Cholinergic Antagonists pharmacology, Cognition drug effects, Cognition physiology, Conditioning, Operant drug effects, Impulsive Behavior drug effects, Male, Rats, Rats, Long-Evans, Reaction Time drug effects, Scopolamine pharmacology, Time Factors, Attention physiology, Choice Behavior physiology, Conditioning, Operant physiology, Housing, Animal, Impulsive Behavior physiology, Reaction Time physiology
- Abstract
Rationale: The 5-choice serial reaction time task (5-CSRTT) is a widely used operant task for measuring attention and motor impulsivity in rodents. Training animals in this task requires an extensive period of daily operant sessions. Recently, a self-paced, automated version of this task has been developed for mice, which substantially reduces training time. Whether a similar approach is effective for rats is currently unknown., Objective: Here, we tested whether attention and impulsivity can be assessed in rats with a self-paced version of the 5-CSRTT., Methods: Operant boxes were connected to home-cages with tunnels. Two groups of rats self-paced their training by means of an automated script. The first group of animals was allowed unlimited access (UA) to start trials in the task; for the second group, trial availability was restricted to the first 2.5 h of the dark cycle (TR). Task parameter manipulations, such as variable inter-trial intervals and stimulus durations as well as pharmacological challenges with scopolamine, were tested to validate the task., Results: Self-paced training took less than 1 week. Animals in the UA group showed higher levels of omissions compared with the TR group. In both protocols, variable inter-trial intervals increased impulsivity, and variable stimulus durations decreased attentional performance. Scopolamine affected cognitive performance in the TR group only., Conclusions: Home-cage-based training of the 5-CSRTT in rats, especially the TR protocol, presents a valid and fast alternative for measuring attention and impulsivity.
- Published
- 2019
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30. Optogenetic and chemogenetic approaches to manipulate attention, impulsivity and behavioural flexibility in rodents.
- Author
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Carr MR, de Vries TJ, and Pattij T
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- Animals, Attention physiology, Behavior, Animal drug effects, Humans, Impulsive Behavior physiology, Receptors, G-Protein-Coupled drug effects, Rodentia, Attention drug effects, Designer Drugs pharmacology, Impulsive Behavior drug effects, Optogenetics
- Abstract
Studies manipulating neural activity acutely with optogenetic or chemogenetic intervention in behaving rodents have increased considerably in recent years. More often, these circuit-level neural manipulations are tested within an existing framework of behavioural testing that strives to model complex executive functions or symptomologies relevant to multidimensional psychiatric disorders in humans, such as attentional control deficits, impulsivity or behavioural (in)flexibility. This methods perspective argues in favour of carefully implementing these acute circuit-based approaches to better understand and model cognitive symptomologies or their similar isomorphic animal behaviours, which often arise and persist in overlapping brain circuitries. First, we offer some practical considerations for combining long-term, behavioural paradigms with optogenetic or chemogenetic interventions. Next, we examine how cell-type or projection-specific manipulations to the ascending neuromodulatory systems, local brain region or descending cortical glutamatergic projections influence aspects of cognitive control. For this, we primarily focus on the influence exerted on attentional and motor impulsivity performance in the (3-choice or) 5-choice serial reaction time task, and impulsive, risky or inflexible choice biases during alternative preference, reward discounting or reversal learning tasks.
- Published
- 2018
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31. Examination of the effects of cannabinoid ligands on decision making in a rat gambling task.
- Author
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Ferland JN, Carr MR, Lee AM, Hoogeland ME, Winstanley CA, and Pattij T
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- Animals, Benzamides pharmacology, Benzoxazines pharmacology, Carbamates pharmacology, Dronabinol pharmacology, Gambling, Impulsive Behavior drug effects, Ligands, Male, Morpholines pharmacology, Naphthalenes pharmacology, Rats, Rats, Wistar, Rimonabant pharmacology, Task Performance and Analysis, Decision Making drug effects, Endocannabinoids physiology, Receptor, Cannabinoid, CB1 physiology
- Abstract
Although exposure to delta-9-tetrahydrocannabinol (THC) is perceived to be relatively harmless, mounting evidence has begun to show that it is associated with a variety of cognitive deficits, including poor decision making. THC-induced impairments in decision making are thought to be the result of cannabinoid CB1 receptor activation, and although clinical literature suggests that chronic activation via THC contributes to perturbations in decision making, acute CB1 receptor modulation has yielded mixed results. Using an animal model to examine how CB1-specific ligands impact choice biases would provide significant insight as to how recruitment of the endocannabinoid system may influence decision making. Here, we used the rat gambling task (rGT), a validated analogue of the human Iowa Gambling Task, to assess baseline decision making preferences in male Wistar rats. After acquisition rGT performance was measured. Animals were challenged with the CB1 receptor antagonist rimonabant, the partial agonist THC, and the synthetic agonist WIN55,212-2. Animals were also treated acutely with the fatty acid amide hydrolase (FAAH) inhibitor URB597 to selectively upregulate the endocannabinoid anandamide. Blockade of the CB1 receptor produced a trend improvement in decision making in animals who preferred the advantageous task options, yet left choice unaffected in risk-prone rats. Neither CB1 receptor agonist had strong effects on decision making, but a high dose THC decreased premature responses, whereas WIN55,212-2 did the opposite. URB597 did not affect task performance. These results indicate that although chronic CB1 receptor activation may be associated with impaired decision making, acute modulation has modest effects on choice and instead may play a substantive role in regulating impulsive responding., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2018
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32. A high working memory load prior to memory retrieval reduces craving in non-treatment seeking problem drinkers.
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Kaag AM, Goudriaan AE, De Vries TJ, Pattij T, and Wiers RW
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- Adolescent, Adult, Alcohol Drinking prevention & control, Animals, Behavior, Addictive diagnosis, Behavior, Addictive prevention & control, Behavior, Addictive psychology, Female, Follow-Up Studies, Humans, Male, Photic Stimulation methods, Single-Blind Method, Young Adult, Alcohol Drinking psychology, Craving physiology, Learning physiology, Memory Consolidation physiology, Memory, Short-Term physiology
- Abstract
Background: Reconsolidation-based interventions have been suggested to be a promising treatment strategy for substance use disorders. In this study, we aimed to investigate the effectiveness of a working memory intervention to interfere with the reconsolidation of alcohol-related memories in a sample of non-treatment seeking heavy drinkers., Methods: Participants were randomized to one of the two conditions that underwent a 3-day intervention: in the experimental condition, a 30-min working memory training was performed immediately after a 15-min memory retrieval session (i.e., within the memory reconsolidation time-window), whereas in the control condition, the working memory training was performed prior to a memory retrieval session., Results: In contrast to our original hypothesis, a high working memory load after memory retrieval did not interfere with the reconsolidation of those memories while a high working memory load prior to memory retrieval (the original control condition) strongly reduced retrieval-induced craving and craving for alcohol at follow-up., Conclusion: Whereas the neurocognitive mechanism behind this effect needs to be further investigated, the current findings suggest that, if replicated, working memory training prior to addiction-related memory retrieval has the potential to become an effective (adjunctive) intervention in the treatment of substance use disorders.
- Published
- 2018
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33. Dissociable effects of cocaine and yohimbine on impulsive action and relapse to cocaine seeking.
- Author
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Broos N, van Mourik Y, Schetters D, De Vries TJ, and Pattij T
- Subjects
- Animals, Choice Behavior drug effects, Cocaine administration & dosage, Conditioning, Operant drug effects, Extinction, Psychological drug effects, Injections, Intravenous, Male, Rats, Rats, Wistar, Reaction Time drug effects, Recurrence, Self Administration, Serial Learning drug effects, Cocaine pharmacology, Cocaine-Related Disorders psychology, Craving drug effects, Impulsive Behavior drug effects, Yohimbine pharmacology
- Abstract
Rationale: A strong association has been demonstrated between various forms of impulsivity and addiction-like behavior in both humans and rats., Objectives: In this study, we investigated how impulsive action, as measured in the 5-choice serial reaction time task (5-CSRTT), is affected during various stages of cocaine taking and seeking and by relapse-provoking stimuli in animals that were trained both in an intravenous cocaine self-administration paradigm and in the 5-CSRTT., Methods: Rats were concurrently trained in the 5-CSRTT and cocaine self-administration protocol, and subsequently, the effects of cocaine (7.5 mg/kg) and the pharmacological stressor yohimbine (1.25 mg/kg) were tested in both paradigms., Results: Cocaine self-administration (5 h/day) transiently altered impulsive action and increased errors of omission in the 5-CSRTT. Pharmacological challenges with cocaine and yohimbine induced increments in impulsive action and reinstated cocaine-seeking responses within the same animals. Further analyses revealed that the effects of cocaine and yohimbine on impulsive action did not correlate with their effects on reinstatement of cocaine seeking., Conclusions: These data suggest that although impulsive action and relapse can be pharmacologically modulated in the same direction within individuals, these effects appear not to be directly coupled.
- Published
- 2017
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34. Deep brain stimulation of the nucleus accumbens core but not shell reduces motivational components of heroin taking and seeking in rats.
- Author
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Schippers MC, Gaastra M, Mesman T, Schetters D, van Mourik Y, Denys D, Pattij T, and De Vries TJ
- Abstract
Background: Deep brain stimulation is explored as a new intervention for treatment-resistant substance use dependence. A candidate brain region is the nucleus accumbens, due to its involvement in reward and motivation. This study aimed to explore effects of NAcore and NAshell deep brain stimulation on aspects of heroin taking and seeking in a self-administration model for rats., Methods: NAcore and NAshell deep brain stimulation was applied during 25 or 100 µg/kg/infusion heroin self-administration on an FR4 schedule of reinforcement and during cue- and heroin-induced reinstatement. In a separate group, effects of NAcore deep brain stimulation on heroin self-administration on a progressive ratio schedule and the first extinction session were examined., Results: NAcore and NAshell deep brain stimulation did not alter heroin self-administration on an FR4 schedule. NAcore deep brain stimulation decreased cue - but not drug-induced reinstatement of heroin seeking, whereas NAshell deep brain stimulation did not affect reinstatement responding. In the second experiment, NAcore deep brain stimulation reduced responding during a progressive ratio schedule of heroin reinforcement. Finally, deep brain stimulation facilitated extinction from day 1 throughout the course of extinction learning., Conclusion: Taken together, the differential effects of NAcore and NAshell deep brain stimulation on heroin taking and seeking are in line with the distinct functional roles of these sub-regions therein. Conditioned cues have been shown to be very powerful stimuli for the persistence of addiction and relapse to drug use. Therefore, the present findings that NAcore deep brain stimulation decreases motivation for heroin taking and cue-conditioned behaviour and facilitates extinction learning are very promising, supporting the positive findings from clinical case studies., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© The Author(s) 2017.)
- Published
- 2017
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35. Deep Brain Stimulation of the Nucleus Accumbens Core Affects Trait Impulsivity in a Baseline-Dependent Manner.
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Schippers MC, Bruinsma B, Gaastra M, Mesman TI, Denys D, De Vries TJ, and Pattij T
- Abstract
Deep brain stimulation (DBS) of the nucleus accumbens (NA) is explored as a treatment for refractory psychiatric disorders, such as obsessive-compulsive disorder (OCD), depressive disorder (MDD), and substance use disorder (SUD). A common feature of some of these disorders is pathological impulsivity. Here, the effects of NAcore DBS on impulsive choice and impulsive action, two distinct forms of impulsive behavior, were investigated in translational animal tasks, the delayed reward task (DRT) and five-choice serial reaction time task (5-CSRTT), respectively. In both tasks, the effects of NAcore DBS were negatively correlated with baseline impulsive behavior, with more pronounced effects in the 5-CSRTT. To further examine the effects of DBS on trait impulsive action, rats were screened for high (HI) and low (LI) impulsive responding in the 5-CSRTT. NAcore DBS decreased impulsive, premature responding in HI rats under conventional conditions. However, upon challenged conditions to increase impulsive responding, NAcore DBS did not alter impulsivity. These results strongly suggest a baseline-dependent effect of DBS on impulsivity, which is in line with clinical observations.
- Published
- 2017
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36. Sustained Attentional States Require Distinct Temporal Involvement of the Dorsal and Ventral Medial Prefrontal Cortex.
- Author
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Luchicchi A, Mnie-Filali O, Terra H, Bruinsma B, de Kloet SF, Obermayer J, Heistek TS, de Haan R, de Kock CP, Deisseroth K, Pattij T, and Mansvelder HD
- Subjects
- Animals, Behavior, Animal, Male, Optogenetics, Rats, Rats, Long-Evans, Attention physiology, Prefrontal Cortex physiology, Pyramidal Cells physiology
- Abstract
Attending the sensory environment for cue detection is a cognitive operation that occurs on a time scale of seconds. The dorsal and ventral medial prefrontal cortex (mPFC) contribute to separate aspects of attentional processing. Pyramidal neurons in different parts of the mPFC are active during cognitive behavior, yet whether this activity is causally underlying attentional processing is not known. We aimed to determine the precise temporal requirements for activation of the mPFC subregions during the seconds prior to cue detection. To test this, we used optogenetic silencing of dorsal or ventral mPFC pyramidal neurons at defined time windows during a sustained attentional state. We find that the requirement of ventral mPFC pyramidal neuron activity is strictly time-locked to stimulus detection. Inhibiting the ventral mPFC 2 s before or during cue presentation reduces response accuracy and hampers behavioral inhibition. The requirement for dorsal mPFC activity on the other hand is temporally more loosely related to a preparatory attentional state, and short lapses in pyramidal neuron activity in dorsal mPFC do not affect performance. This only occurs when the dorsal mPFC is inhibited during the entire preparatory period. Together, our results reveal that a dissociable temporal recruitment of ventral and dorsal mPFC is required during attentional processing.
- Published
- 2016
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37. Prefrontal cortical neuregulin-ErbB modulation of inhibitory control in rats.
- Author
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Loos M, Schetters D, Hoogeland M, Spijker S, de Vries TJ, and Pattij T
- Subjects
- Animals, Attention drug effects, Behavior, Animal drug effects, Choice Behavior drug effects, ErbB Receptors antagonists & inhibitors, Impulsive Behavior drug effects, Male, Morpholines pharmacology, Prefrontal Cortex drug effects, Prefrontal Cortex physiology, Protein Kinase Inhibitors pharmacology, Pyrimidines pharmacology, Rats, Reaction Time drug effects, ErbB Receptors metabolism, Neuregulins metabolism, Prefrontal Cortex metabolism
- Abstract
Impulse control disturbances are key features of various neuropsychiatric and neurological disorders, such as attention-deficit/hyperactivity disorder, drug addiction, Parkinson disease and schizophrenia. Whereas over the last years accumulating evidence has highlighted monoaminergic modulation of the processes underlying impulse control, investigating novel mechanisms beyond monoamines may provide new intervention strategies to ameliorate impulse control disturbances. Recent work has associated the neuregulin (Nrg)-ErbB pathway with several neuropsychiatric diseases, as well as indicated its involvement in murine measures of impulse control. The aim of the present study was to investigate whether this Nrg-ErbB signaling pathway also modulates impulsive action in rats. To this end, a group of rats was trained in the 5-choice serial reaction time task (5-CSRTT), an operant paradigm that provides measures of visuospatial attention and inhibitory control processes. Upon stable baseline performance, the ErbB tyrosine kinase receptor inhibitor JNJ-28871063 (JNJ) was intracranially infused into the medioprefrontal cortex prior to test sessions. Results showed that JNJ dose-dependently improved measures of impulsive action. Importantly, other measures in the 5-CSRTT reflecting visuospatial attention or aspects of motivational behavior were not altered by JNJ. In conclusion, the present data strengthen a role for the Nrg-ErbB4 pathway in the prefrontal cortex in cognitive functioning, and in particular point towards involvement in the processes underlying impulse control., (Copyright © 2016 Elsevier B.V. All rights reserved.)
- Published
- 2016
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38. Compulsivity in obsessive-compulsive disorder and addictions.
- Author
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Figee M, Pattij T, Willuhn I, Luigjes J, van den Brink W, Goudriaan A, Potenza MN, Robbins TW, and Denys D
- Subjects
- Animals, Behavior, Addictive diagnosis, Behavior, Addictive psychology, Behavior, Addictive therapy, Combined Modality Therapy, Compulsive Behavior diagnosis, Compulsive Behavior psychology, Compulsive Behavior therapy, Compulsive Personality Disorder diagnosis, Compulsive Personality Disorder psychology, Compulsive Personality Disorder therapy, Corpus Striatum physiopathology, Diagnostic and Statistical Manual of Mental Disorders, Frontal Lobe physiopathology, Habits, Humans, Nerve Net physiopathology, Obsessive-Compulsive Disorder diagnosis, Obsessive-Compulsive Disorder psychology, Obsessive-Compulsive Disorder therapy, Punishment, Reinforcement, Psychology, Reward, Substance-Related Disorders diagnosis, Substance-Related Disorders psychology, Substance-Related Disorders therapy, Terminology as Topic, Behavior, Addictive physiopathology, Compulsive Behavior physiopathology, Compulsive Personality Disorder physiopathology, Evidence-Based Medicine, Models, Neurological, Obsessive-Compulsive Disorder physiopathology, Substance-Related Disorders physiopathology
- Abstract
Compulsive behaviors are driven by repetitive urges and typically involve the experience of limited voluntary control over these urges, a diminished ability to delay or inhibit these behaviors, and a tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is not only a central characteristic of obsessive-compulsive disorder (OCD) but is also crucial to addiction. Based on this analogy, OCD has been proposed to be part of the concept of behavioral addiction along with other non-drug-related disorders that share compulsivity, such as pathological gambling, skin-picking, trichotillomania and compulsive eating. In this review, we investigate the neurobiological overlap between compulsivity in substance-use disorders, OCD and behavioral addictions as a validation for the construct of compulsivity that could be adopted in the Research Domain Criteria (RDoC). The reviewed data suggest that compulsivity in OCD and addictions is related to impaired reward and punishment processing with attenuated dopamine release in the ventral striatum, negative reinforcement in limbic systems, cognitive and behavioral inflexibility with diminished serotonergic prefrontal control, and habitual responding with imbalances between ventral and dorsal frontostriatal recruitment. Frontostriatal abnormalities of compulsivity are promising targets for neuromodulation and other interventions for OCD and addictions. We conclude that compulsivity encompasses many of the RDoC constructs in a trans-diagnostic fashion with a common brain circuit dysfunction that can help identifying appropriate prevention and treatment targets., (Copyright © 2016. Published by Elsevier B.V.)
- Published
- 2016
- Full Text
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39. Serotonin and inhibitory response control: focusing on the role of 5-HT(1A) receptors.
- Author
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Pattij T and Schoffelmeer AN
- Subjects
- Animals, Serotonin Receptor Agonists pharmacology, Inhibition, Psychological, Receptors, Serotonin metabolism
- Abstract
Disturbances in behavioral inhibition are key features in several neurological and psychiatric disorders, such as attention-deficit/hyperactivity disorder, Parkinson's disease and substance use disorders. Therefore, elucidating the neural correlates of inhibitory control processes is crucial for developing novel treatment strategies to ameliorate the symptomatology of these disorders and to improve the quality of life. The development of preclinical translational paradigms to study inhibitory control processes has greatly enhanced our neurobiological understanding of these cognitive processes. Over the last decades, emphasis has been mainly on monoamines including dopamine and serotonin and their contribution to behavioral inhibition. This short review will focus on the involvement of the serotonergic system, and in particular serotonin1A receptors, in inhibitory control processes., (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
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