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In this study we sought to determine the effect of daily sucrose consumption in young rats on their subsequent performance in tasks that involve the prefrontal cortex and hippocampus. High levels of sugar consumption have been associated with the development of obesity, however less is known about how sugar consumption influences behavioral control and high-order cognitive processes. Of particular concern is the fact that sugar intake is greatest in adolescence, an important neurodevelopmental period. We provided sucrose to rats when they were progressing through puberty and adolescence. Cognitive performance was assessed in adulthood on a task related to executive function, a rodent analog of the Stroop task. We found that sucrose-exposed rats failed to show context-appropriate responding during incongruent stimulus compounds presented at test, indicative of impairments in prefrontal cortex function. Sucrose exposed rats also showed deficits in an on object-in-place recognition memory task, indicating that both prefrontal and hippocampal function was impaired. Analysis of brains showed a reduction in expression of parvalbumin-immunoreactive GABAergic interneurons in the hippocampus and prefrontal cortex, indicating that sucrose consumption during adolescence induced long-term pathology, potentially underpinning the cognitive deficits observed. These results suggest that consumption of high levels of sugar-sweetened beverages by adolescents may also impair neurocognitive functions affecting decision-making and memory, potentially rendering them at risk for developing mental health disorders., (© 2015 Reichelt et al.; Published by Cold Spring Harbor Laboratory Press.)

Memories are not static imprints of past experience, but rather are dynamic entities which enable us to predict outcomes of future situations and inform appropriate behaviours. In order to maintain the relevance of existing memories to our daily lives, memories can be updated with new information via a process of reconsolidation. In this review we describe recent experimental advances in the reconsolidation of both appetitive and aversive memory, and explore the neuronal mechanisms that underpin the conditions under which reconsolidation will occur. We propose that a prediction error signal, originating from dopaminergic midbrain neurons, is necessary for destabilisation and subsequent reconsolidation of a memory., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Both obesity and over-consumption of palatable high fat/high sugar "cafeteria" diets in rats has been shown to induce cognitive deficits in executive function, attention and spatial memory. Adult male Sprague-Dawley rats were fed a diet that supplemented standard lab chow with a range of palatable foods eaten by people for 8 weeks, or regular lab chow. Memory was assessed using a trace fear conditioning procedure, whereby a conditioned stimulus (CS) is presented for 10s and then 30s after its termination a foot shock (US) is delivered. We assessed freezing to the CS (flashing light) in a neutral context, and freezing in the context associated with footshock. A dissociation was observed between levels of freezing in the context and to the CS associated with footshock. Cafeteria diet fed rats froze less than control chow fed rats in the context associated with footshock (P<0.01), indicating that encoding of a hippocampus-dependent context representation was impaired in these rats. Conversely, cafeteria diet fed rats froze more (P<0.05) to the CS than chow fed rats, suggesting that when hippocampal function was compromised the cue was the best predictor of footshock, as contextual information was not encoded. Dorsal hippocampal mRNA expression of inflammatory and neuroplasticity markers was analysed at the end of the experiment, 10 weeks of diet. Of these, mRNA expression of reelin, which is known to be important in long term potentiation and neuronal plasticity, was significantly reduced in cafeteria diet fed rats (P=0.003). This implicates reductions in hippocampal plasticity in the contextual fear memory deficits seen in the cafeteria diet fed rats., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A range of animal and human data demonstrates that excessive consumption of palatable food leads to neuroadaptive responses in brain circuits underlying reward. Unrestrained consumption of palatable food has been shown to increase the reinforcing value of food and weaken inhibitory control; however, whether it impacts upon the sensory representations of palatable solutions has not been formally tested. These experiments sought to determine whether exposure to a cafeteria diet consisting of palatable high fat foods impacts upon the ability of rats to learn about food-associated cues and the sensory properties of ingested foods. We found that rats fed a cafeteria diet for 2 weeks were impaired in the control of Pavlovian responding in accordance to the incentive value of palatable outcomes associated with auditory cues following devaluation by sensory-specific satiety. Sensory-specific satiety is one mechanism by which a diet containing different foods increases ingestion relative to one lacking variety. Hence, choosing to consume greater quantities of a range of foods may contribute to the current prevalence of obesity. We observed that rats fed a cafeteria diet for 2 weeks showed impaired sensory-specific satiety following consumption of a high calorie solution. The deficit in expression of sensory-specific satiety was also present 1 week following the withdrawal of cafeteria foods. Thus, exposure to obesogenic diets may impact upon neurocircuitry involved in motivated control of behavior.

Three experiments used rats to examine the effect of a single bout of voluntary activity (wheel running) on the acquisition, extinction, and reconsolidation of context conditioned fear. In Experiment 1, rats provided with access to a wheel for 3 h immediately before or after a shocked exposure to a context froze more when tested in that context than rats provided with access to the wheels 6 h after the shocked exposure or rats not provided with access to the wheels. In Experiment 2, rats provided with access to the wheels immediately before or after a nonshocked exposure to the conditioned context froze less when tested in that context than rats provided with access to the wheels 6 h after the nonshocked exposure or rats not provided with access to the wheels. In Experiment 3, rats provided with access to wheels immediately after an extended nonshocked exposure to the conditioned context again froze less, whereas rats provided with access to the wheels after a brief nonshocked exposure froze more on the subsequent test than sedentary controls. These results show that a single bout of running can enhance acquisition, extinction, and reconsolidation of context conditioned fear.

Previous research demonstrates that disruption of forebrain dopamine systems impairs the use of high-order information to guide goal-directed performance, and that this deficit may be related to impaired use of task-setting cues in patients with schizophrenia. Such deficits can be interrogated through conflict resolution, which has been demonstrated to be sensitive to prefrontal integrity in rodents. We sought to examine the effects of acute systemic d-amphetamine administration on the contextual control of response conflict in rats, and whether deficits were reversed through pre-treatment with clozapine or the D₁/D₂ antagonist α-flupenthixol. Acute d-amphetamine (1.5 mg/kg) disrupted the utilisation of contextual cues; therefore rats were impaired during presentation of stimulus compounds that require conflict resolution. Evidence suggested that this effect was attenuated through pre-treatment with the atypical antipsychotic clozapine (5.0 mg/kg), but not the typical antipsychotic α-flupenthixol (0.25 mg/kg), at doses previously shown to attenuate d-amphetamine-induced cognitive deficits. These studies therefore demonstrate a potentially viable model of disrupted executive function such as that seen in schizophrenia.

Animal models are making an increasing contribution to our understanding of the psychology and brain mechanisms underlying behavioral inhibition and impulsivity. The aim here was to develop, for the first time, a mouse analog of the stop-signal reaction time task with high translational validity in order to be able to exploit this species in genetic and molecular investigations of impulsive behaviors. Cohorts of mice were trained to nose-poke to presentations of visual stimuli. Control of responding was manipulated by altering the onset of an auditory 'stop-signal' during the go response. The anticipated systematic changes in action cancellation were observed as stopping was made more difficult by placing the stop-signal closer to the execution of the action. Excitotoxic lesions of medial prefrontal cortex resulted in impaired stopping, while the clinically effective drugs methylphenidate and atomoxetine enhanced stopping abilities. The specific 5-HT2C receptor antagonist SB242084 also led to enhanced response control in this task. We conclude that stop-signal reaction time task performance can be successfully modeled in mice and is sensitive to prefrontal cortex dysfunction and drug treatments in a qualitatively similar manner to humans and previous rat models. Additionally, using this model we show novel and highly discrete effects of 5-HT2C receptor antagonism that suggest manipulation of 5-HT2C receptor function may be of use in correcting maladaptive impulsive behaviors and provide further evidence for dissociable contributions of serotonergic transmission to response control.

Memory reconsolidation has been observed across species and in a number of behavioral paradigms. The majority of memory reconsolidation studies have been carried out in Pavlovian fear conditioning and other aversive memory settings, with potential implications for the treatment of post-traumatic stress disorder. However, there is a growing literature on memory reconsolidation in appetitive reward-related memory paradigms, including translational models of drug addiction. While there appears to be substantial similarity in the basic phenomenon and underlying mechanisms of memory reconsolidation across unconditioned stimulus valence, there are also notable discrepancies. These arise both when comparing aversive to appetitive paradigms and also across different paradigms within the same valence of memory. We review the demonstration of memory reconsolidation across different aversive and appetitive memory paradigms, the commonalities and differences in underlying mechanisms and the conditions under which each memory undergoes reconsolidation. We focus particularly on whether principles derived from the aversive literature are applicable to appetitive settings, and also whether the expanding literature in appetitive paradigms is informative for fear memory reconsolidation.

Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Through the process of reconsolidation, memories can be updated to maintain their relevance. To reconsolidate, a memory must first be destabilized in a process that we have hypothesized is initiated by a prediction error signal. Here we demonstrate that dysregulation of ventral tegmental area (VTA) signaling, which is thought to mediate prediction errors, prevented the destabilization of an appetitive goal-tracking memory in rats. We additionally show that intra-VTA infusion of either the competitive NMDA antagonist AP5 or the noncompetitive NMDA antagonist MK-801 does not selectively disrupt reconsolidation, indicating that the VTA may not be an important neural locus of reconsolidation-related neural plasticity.

Rationale: Discrepancies in an expected outcome have been demonstrated to result in modification of behaviour in both appetitive and aversive conditioning settings., Objectives: In this study, we sought to establish whether overexpectation generated from compound conditioning with two previously rewarded stimuli was able to induce memory destabilisation and subsequent reconsolidation in a Pavlovian conditioned approach setting., Results: It was shown that 4 days, but not 1 day, of overexpectation training was required to induce memory reconsolidation, and this was disrupted by application of the NMDA subtype of glutamate receptor antagonist MK-801 prior to overexpectation training, but not by MK-801 application 6 h post-training., Conclusions: These data provide evidence that the memories underlying Pavlovian conditioned approach do undergo reconsolidation and that such reconsolidation can be triggered by overexpectation. Therefore, the updating of appetitive conditioned stimulus and unconditioned stimulus associations underpinning conditioned responding in manners other than extinction training is likely achieved through memory reconsolidation.

Despite extensive evidence that appetitive memories undergo reconsolidation, two notable failures to observe reconsolidation have been reported: instrumental responding and goal-tracking. However, these studies do not provide conclusive evidence for a lack of memory reconsolidation due to the numerous boundary conditions that dictate whether a memory will undergo reconsolidation. In this study we sought to reexamine reconsolidation in an appetitive, Pavlovian conditioned approach procedure and the behavioral boundary conditions within which memories are destabilized and reconsolidated. This study demonstrated that a Pavlovian goal-tracking memory, previously thought to be resistant to destabilization, will undergo memory reconsolidation under discrete conditions that favor reconsolidation as opposed to extinction, and that this is dependent on the amount of training rats received. With restricted training, systemic administration of MK-801 impaired memory extinction. In contrast, with more extended training, MK-801 administration impaired memory reconsolidation. We also demonstrate that behavioral boundary conditions that exist for appetitive memory reconsolidation are much more complex than simple parametric calculations. Moreover, extinction per se is not a boundary on reconsolidation, in that MK-801 also has no behavioral effect under some conditions.

Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1α gene (but not the neurexin-1β gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1α provides direct access to the biological effects of neurexin-1α disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1α in schizophrenia and ASD, and consider how genetic disruption of neurexin-1α may underpin the neuropathology contributing to these distinct neurodevelopmental disorders., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Instrumental performance in rats with hippocampal lesions is insensitive to the degradation of action-outcome contingencies, but sensitive to the effects of selective devaluation by satiation. One interpretation of this dissociation is that damage to the hippocampus impairs the formation of context-outcome associations upon which the effect of contingency degradation, but not selective satiation, relies. Here, we provide a direct assessment of this interpretation, and showed that conditioned responding to contexts did not show sensitivity to selective satiation (Experiment 1), and confirmed that instrumental performance was sensitive to selective satiation (Experiment 2) following hippocampal cell loss., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The papaverine test has been widely used as a diagnostic procedure in erectile impotence. However, when patients do not achieve full erection on the test, it is necessary to differentiate between insufficient inflow and excessive outflow. Gravity cavernosometry is a method designed to evaluate the pressure responses in the corpora when they are subjected to a constant infusion pressure. The infusion flow is of minor significance. The intracavernous pressure (ICP) was measured in cadavers, in psychogenically impotent patients and in patients with arteriogenic impotence, following administration of papaverine and gravity perfusion. During perfusion in cadavers and in psychogenic patients, the ICP showed values above 110 cm H2O, while in arteriogenic patients the values ranged from 30 to 141 cm H2O. In the arteriogenic group, 11/20 patients had an ICP lower than 110 during perfusion. There was no correlation between the pre-perfusion pressure and the final pressure with perfusion. Gravity cavernosometry is a simple, cost-effective and reliable method for the assessment of corporeal competence.

Twenty-three patients with corpora cavernosa incompetence responsive to perineal compression were submitted to surgical exclusion of the crural ending of the corpora cavernosa. There were two mild complications: perineal hematoma and incisional pain for 10 days. At the end of the first month, 65% of the patients claimed better erections, and the late good results were 47.7%, with an average follow-up period of 18.9 months. Three of the failed cases were later submitted to a penile prosthesis implantation.

Blood drainage of the corpora cavernosa is made by the deep dorsal vein and by the deep crural veins. The root of the corpora can be compressed against the ischium during papaverine test or cavernometry. In a series of patients with cavernosal leakage, this maneuver demonstrated that the crural edge of the corpora is the point of leakage in many of them. Exclusion of the crural edge by ligation of the corpora proximal to the entrance of the arterial supply caused improvement of erections in 7 of 8 patients.

Owing to the vasoconstrictive effect of nicotine, smoking may potentially interfere in the results of the drug-induced erection test for papaverine hydrochloride. To investigate the effect of smoking on this test, 12 patients between 22 and 65 years old underwent the following protocol: phase 1--intracavernous injection of 100 mg. papaverine hydrochloride with measurement of intracavernous pressure by puncture with a 19 caliber butterfly needle attached to an aneroid manometer and phase 2--1 week after the initial test the procedure was repeated after the patient smoked 2 cigarettes. In phase 1 all men obtained a full erection, compared to only 4 in phase 2. The average intracavernous pressures were 85.83 and 53.50 mm. Hg, respectively, in phases 1 and 2 (p less than 0.01). We conclude that cigarette smoking, probably through nicotine, interferes with the drug-induced erection test, which might explain some false negative results.