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The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

The HEALthy Brain and Child Development (HBCD) study will establish a large cohort of pregnant women from regions of the country significantly affected by the opioid crisis and follow them and their children for at least 10 years. Findings from this cohort will help researchers understand normative childhood brain development as well as the long-term impact of prenatal and postnatal opioid and other drug and environmental exposures. The study will collect data on pregnancy and fetal development; infant and early childhood structural and functional brain imaging; anthropometrics; medical history; family history; biospecimens; and social, emotional, and cognitive development. Knowledge gained from this research will be critical to help predict and prevent some of the known effects of prenatal and postnatal exposure to certain drugs or environmental exposures, including risk for future substance use, mental disorders, and other behavioral and developmental problems. In this special issue, a subset of investigators that received funding for planning grants for the HBCD study provide careful guidelines and frameworks for study design, recruitment and retention of vulnerable populations, culturally sensitive practices, and biospecimen and neurodevelopmental assessment recommendations gathered in feasibility studies that will help inform the full HBCD study planned to begin recruitment in 2022.

Commentary: Recognizing the increasing diversity of cannabis products and their expanded use, Freeman & Lorenzetti propose a standard unit dose of 5 mg 9‐tetrahydrocannabinol (THC) to be used for all cannabis products, regardless of method of administration. They argue that a standard dose would help to guide consumers towards safer patterns of cannabis use. The National Institute on Drug Abuse (NIDA) strongly supports the need for a standardized measure to facilitate research, and this was a key recommendation from NIDA's Cannabis Policy Research Council Workgroup....

Adolescence is a time of dramatic changes in brain structure and function, and the adolescent brain is highly susceptible to being altered by experiences like substance use. However, there is much we have yet to learn about how these experiences influence brain development, how they promote or interfere with later health outcomes, or even what healthy brain development looks like. A large longitudinal study beginning in early adolescence could help us understand the normal variability in adolescent brain and cognitive development and tease apart the many factors that influence it. Recent advances in neuroimaging, informatics, and genetics technologies have made it feasible to conduct a study of sufficient size and scope to answer many outstanding questions. At the same time, several Institutes across the NIH recognized the value of collaborating in such a project because of its ability to address the role of biological, environmental, and behavioral factors like gender, pubertal hormones, sports participation, and social/economic disparities on brain development as well as their association with the emergence and progression of substance use and mental illness including suicide risk. Thus, the Adolescent Brain Cognitive Development study was created to answer the most pressing public health questions of our day. Keywords: Adolescent, Brain development, Neuroimaging, Longitudinal, Substance use, Mental health

Importance Incidental findings (IFs) are unexpected abnormalities discovered during imaging and can range from normal anatomic variants to findings requiring urgent medical intervention. In the case of brain magnetic resonance imaging (MRI), reliable data about the prevalence and significance of IFs in the general population are limited, making it difficult to anticipate, communicate, and manage these findings. Objectives To determine the overall prevalence of IFs in brain MRI in the nonclinical pediatric population as well as the rates of specific findings and findings for which clinical referral is recommended. Design, setting, and participants This cohort study was based on the April 2019 release of baseline data from 11 810 children aged 9 to 10 years who were enrolled and completed baseline neuroimaging in the Adolescent Brain Cognitive Development (ABCD) study, the largest US population-based longitudinal observational study of brain development and child health, between September 1, 2016, and November 15, 2018. Participants were enrolled at 21 sites across the US designed to mirror the demographic characteristics of the US population. Baseline structural MRIs were centrally reviewed for IFs by board-certified neuroradiologists and findings were described and categorized (category 1, no abnormal findings; 2, no referral recommended; 3; consider referral; and 4, consider immediate referral). Children were enrolled through a broad school-based recruitment process in which all children of eligible age at selected schools were invited to participate. Exclusion criteria were severe sensory, intellectual, medical, or neurologic disorders that would preclude or interfere with study participation. During the enrollment process, demographic data were monitored to ensure that the study met targets for sex, socioeconomic, ethnic, and racial diversity. Data were analyzed from March 15, 2018, to November 20, 2020. Main outcomes and measures Percentage of children with IFs in each category and prevalence of specific IFs. Results A total of 11 679 children (52.1% boys, mean [SD] age, 9.9 [0.62] years) had interpretable baseline structural MRI results. Of these, 2464 participants (21.1%) had IFs, including 2013 children (17.2%) assigned to category 2, 431 (3.7%) assigned to category 3, and 20 (0.2%) assigned to category 4. Overall rates of IFs did not differ significantly between singleton and twin gestations or between monozygotic and dizygotic twins, but heritability analysis showed heritability for the presence or absence of IFs (h2 = 0.260; 95% CI, 0.135-0.387). Conclusions and relevance Incidental findings in brain MRI and findings with potential clinical significance are both common in the general pediatric population. By assessing IFs and concurrent developmental and health measures and following these findings over the longitudinal study course, the ABCD study has the potential to determine the significance of many common IFs.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.HighlightsAn overview of the MRI processing pipeline for the ABCD StudyA discussion on the challenges of large, multisite population studiesA methodological reference for users of publicly shared data from the ABCD Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9–10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

Social attitudes and cultural norms around the issue of substance abuse are shifting rapidly around the world, leading to complex and unpredictable consequences. On the positive side, efforts to more intensely disseminate the scientific evidence for the many connections between chronic substance use and the emergence of measurable and discrete brain dysfunctions, has ushered in an evolving climate of acceptance and a new era of improved access to more effective interventions, at least in the United States. On the negative side, there has been a steady erosion in the public perception of the harms associated with the use of popular drugs, especially cannabis. This worrisome trend has sprouted at the convergence of several forces that have combined, more or less fortuitously, to effectively change long-standing policies away from prohibition and toward decriminalization or legalization. These forces include the outsized popularity of the cannabis plant among recreational users, the unflagging campaign by corporate lobbyists and patient advocates to mainstream its medicinal use, and the honest realization in some quarters of the deleterious impact of the drug war and its draconian cannabis laws, in particular, on society's most vulnerable populations. Updating drug policies is a desirable goal, and significant changes may indeed be warranted. However, there is a real concern when policy changes are hurriedly implemented without the required input from the medical, scientific, or policy research communities. Regardless of how well intentioned, such initiatives are bound to magnify the potential for unintended adverse consequences in the form of far ranging health and social costs. To minimize this risk, science must be front and center in this important policy debate. Here, we review the state of the science on cannabis and cannabinoid health effects, both adverse and therapeutic. We focus on the prevalence of use in different populations, the mechanisms by which cannabis exerts its effects (i.e., via the endocannabinoid system), and the double-edged potential of this system to inspire new medications, on one hand, and to cause short and long term harmful effects on the other. By providing knowledge of cannabis' broad ranging effects, we hope to enable better decision making regarding cannabis legislation and policy implementation.

Tolerance development after successful long-term treatment of bipolar disorder is under recognized, as are ways to prevent or show its occurrence or reverse it once it has occurred. We review the clinical literature which suggests that tolerance can develop to most treatment approaches in bipolar illness and present an animal model of tolerance development to anticonvulsant effects of carbamazepine or lamotrigine on amgydala-kindled seizures. In this model tolerance does not have a pharmacokinetic basis, but is contingent upon the drug being present in the brain at the time of amygdala stimulation. The occurrence of seizures in the absence of drug is sufficient to reverse tolerance and re-establish anticonvulsant efficacy. Based on the model, we hypothesize that some episode-induced compensatory adaptive changes in gene expression fail to occur in tolerant subjects and that episodes off medication re-induce these changes and renew drug effectiveness. Approaches that slow or reverse tolerance development in the animal model are reviewed so that they can be tested for their applicability in the clinic. Criteria for assessing tolerance development are offered in the hope that this will facilitate a more systemic literature about its prevalence, prevention, and reversal. Careful longitudinal monitoring of episode occurrence is essential to understanding tolerance development in the affective disorder and its treatment.

Substance abuse among older adults has received little attention in the past, presumably because this population has traditionally accounted for only a small percentage of the drug abuse problem in the United States. The aging of the baby boomer generation (born 1946-1964), however, will soon swell the ranks of older adults and dramatically alter the demography of American society. Several observations suggest that this expansion will likely be accompanied by a precipitous increase in the abuse of drugs, including prescription medications and illicit substances, among older adults. While it is now evident that the brain changes continuously across life, how drugs of abuse interact with these age-related changes remains unclear. The dynamic nature of brain function, however, suggests that substance abuse during older age may augment the risks and require unique considerations for diagnosis and treatment. In addition to describing current and projected prevalence estimates of substance abuse among older adults, the present review discusses how aging affects brain systems involved in drug abuse, and explores the potential impact of drug abuse on the aging brain. Future directions for substance abuse research among older adults will also be considered.

As marijuana use becomes legal in some states, the dominant public opinion is that marijuana is a harmless source of mood alteration. Although the harms associated with marijuana use have not been well studied, enough information is available to cause concern.

This study examines forms of activity-dependent synaptic plasticity in the basolateral amygdalain vitroand demonstrates that a brief high frequency stimulus (HFS) train can induce a switch in the direction of the enduring change in synaptic strength induced by subsequent low-frequency stimulation (LFS). LFS (1 Hz, 15 min) of the external capsule (EC) induced a persistent 1.7-fold enhancement in the amplitude of synaptic potentials recorded intracellularly in basolateral amygdala neurons. The enhancement occurred gradually during the stimulation and was maintained for >30 min after termination of the stimulus train. LFS-induced enduring synaptic facilitation was not affected by the NMDA receptor antagonistd(−)-2-amino-5-phosphonopentanoate (APV; 100 μm). Brief high-frequency EC stimulation (HFS; 100 Hz, 1 sec) induced APV-sensitive short-term potentiation (2.5-fold) that generally decayed within 10 min. When LFS was applied after recovery from the short-term potentiating effect of HFS (HFS/LFS), there was an initial transient (m) prevented the HFS-dependent switch from synaptic facilitation to depression. Thus, LFS in thein vitroamygdala slice can induce either enduring synaptic potentiation or depression, depending on whether a priming HFS train has been applied. This experience-dependent switch, a novel form of metaplasticity, is not dependent on NMDA receptors but may require group II metabotropic glutamate receptors. In the amygdala, experiential modification of activity-dependent long-term synaptic plasticity adds flexibility to the ways in which synaptic strength can be modified and could play a role in diverse amygdala-dependent processes, including the formation, storage, and extinction of emotional memory and the regulation of epileptogenesis.

Summary: Carbamazepine (CBZ) blocks the development of local anesthetic seizures kindled by cocaine and lidocaine. Cocaine and lidocaine release corticotropin-releasing hormone (CRH) in hypothalamic cell cultures, and this effect is also blocked by CBZ. Because CRH administered intracerebroventricularly (i.c.v.) can produce seizures, its potential role in the development of cocaine seizures and in the anticonvulsant effects of CBZ was studied. CRH (at doses of 5, 10, and 100 μg) potentiated cocaine-kindled seizure development and lethality in a dose-related fashion. CRH also reversed the effects of CBZ on cocaine kindling and lethality, but only at the highest doses, which also affected cocaine kindling. Thus, a selective role for CRH in the anticonvulsant effects of CBZ was not demonstrated. The findings suggest a potentially important role for CRH in exacerbating cocaine-seizure evolution and its associated lethality and confirm the inhibition of cocaine kindling and lethality by CBZ. RESUMEN La carbamacepina (CBZ) bloquea el desarrollo de ataques locales anestesicos condicionados (kindled) con cocaina y lidocaina. La cocaina y lidocaina generan la hormona liberadora de corticotropina (CRH) en cultivos de celulas hipotalamicas y este efecto tambien lo bloquea la CBZ. Puesto que la administracion intracerebroventricular (i.c.v.) de CRH puede producir ataques, se ha estudiado su posible participacion en el desarrollo de 10s ataques producidos por cocaina y 10s efectos anticonvulsivos de la CBZ. La CRH (a dosis de 5, 10 y 100 μg) potencia el desarrollo de ataques condicionados (kindled) y la mortalidad de una manera relacionada con la dosis. La CRH tambien invierte los efectos de la CBZ sobre el “kindling” de la cocaina y la mortalidad pero solamente en las dosis mas elevadas que tambien afectaron el “kindling” de la cocaina. Asi pues, no se ha demostrado un papel selectivo de la CRH sobre los efectos anticonvulsivos de la CBZ. Estos hallazgos sugieren la existencia de un papel potencialmente importante de la CRH en la exacerbacion de la evolucion de los ataques inducidos por cocaina y en la mortalidad asociada y confirman la inhibicion del “kindling” producido por la cocaina y la mortalidad producida por la CBZ. ZUSAMMENFASSUNG Carbamazepin (CBZ) blockiert die Entwicklung von Anfallen, die durch Kokain- und Lidocain-Kindling entstehen. Kokain und Lidocain setzen Corticotropin-Releasing Hormon (CRH) in hy pothalamischen Zellkulturen frei, und dieser Effekt wird ebenfalls durch CBZ blockiert. Da intraventrikular (i.c.v.) gegebenes CRH Anfalle produzieren kann, wurde seine mogliche Rolle bei der Entwicklung von Kokain-Anfallen und der antikonvulsiven Wirkung von CBZ untersucht. CRH (in Dosierungen von 5, 10 und 100 μg) verstarkte die Kokaingekindelte Anfallsentwicklung und Letalitat in einer dosisabhangigen Weise. CRH kehrte die CBZ-Wirkung auf Kokain-kindling und Letalitat um, jedoch nur in den hochsten Dosen, die ebenfalls das Kokain-Kindling beeinfluβten. Demnach wurde eine selektive Rolle von CRH bei der antikonvulsiven Wirkung von CBZ nicht gezeigt. Die Befunde demonstrieren eine moglicherweise wichtige Rolle von CRH in der Entwicklung von Kokain-Anfallen und der assoziierten Letalitat und bestatigen die Inhibition von Kokain-Kindling und Letalitat durch CBZ.

The relationship of the timing of drug administration to anticonvulsant efficacy against amygdala kindled seizures was studied. During kindling development, rats received carbamazepine (CBZ, 15mg/kg) before (CBZ-before) or after each amygdala stimulation (CBZ-after). After kindling to full seizures, when all animals were given CBZ before the stimulation, only the CBZ-after group showed a good anticonvulsant response. The rats that had received CBZ before (during development of kindled seizures) remained unresponsive to CBZ treatment (contingent inefficacy). When drug-naive or CBZ-after animals repeatedly received CBZ before electrical stimulation, they developed tolerance to its anticonvulsant effects (contingent tolerance). The tolerance could be reversed by a period of treatment with CBZ-after or by kindling the animal drug-free, but not by CBZ administration alone or by time off from both drug and seizures. These findings suggest that inefficacy and tolerance to CBZ may be affected by the temporal contingencies of drug administration and that responsiveness can be reinstated by altering these contingencies.

[3H]Nimodipine and high-affinity [125I]omega-conotoxin GVIA (CgTX) binding were investigated in membranes from rat cerebral cortex, cerebellum, and hippocampus after electrically and chemically induced seizures. Animals were decapitated 30 min after a single electroconvulsive shock (ECS) or lidocaine-induced seizure and 24 h after the last of 10 once-daily ECS or six once-daily lidocaine-induced seizures. After a single ECS, [3H]nimodipine and [125I]CgTX binding sites decreased in cerebral cortex (by 10% and 17%, respectively). A downregulation of [3H]nimodipine binding sites in hippocampus occurred after single and repeated lidocaine-induced seizures (by 24% and 11%, respectively), whereas [125I]CgTX binding remained unaltered. An earlier report on changes in [3H]nitrendipine binding after chronic ECS in cortex and hippocampus was not confirmed.

Summary: The effects of feeding a diet enriched in caffeine or carbamazepine (CBZ) were investigated in rats in a quantitative autoradiographic study of adenosine Al receptors (labeled by [3H]cyclohexyladenosine, [3H]CHA) and adenylate cyclase (labeled by pHJforskolin). Although regional distribution of [3H]CHA and [3H]-forskolin binding sites differed in some areas, chronic CBZ as well as chronic caffeine upregulated both of them. The changes in receptor densities occurred in the same brain microregions, suggesting that caffeine and CBZ act as antagonists at similar subpopulations of adenosine Al receptors and [3H]forskolin binding sites. Therefore, a selective interaction of these two drugs with distinct adenosine Al receptors (and adenylate cyclase) probably does not explain the differential effects of caffeine and CBZ on neuronal activity. RESUME Les consequences d'une alimentation enrichie en cafeine ou en carbamazepine ont ete examinees chez le rat au cours d'une etude autoradiographique quantitative des recepteurs Al de l'adenosine (marques par la cyclohexyladenosine[3H], [3H]CHA) et de l'adenylate cyclase (marquee par la forskoline[3H]). Quelque soit la distribution des sites de liaison de la CHA[3H] et de la forskoline[3H] different dans quelques structures, un traitement chronique a la carbamazepine, comme a la cafeine, augmente le nombre de ces deux types de recepteurs. Les changements de densite des sites de liaison ont ete observes dans les memes microregions cerebrales, suggerant que la cafeine et la carbamazepine agissent comme antagonistes au niveau des memes subpopulations de recepteurs Al de l'adenosine et de sites de liaison de la forskoline[3H]. Ainsi, une interaction selective de ces deux drogues avec des recepteurs distincts (Al de l'adenosine et aussi de l'adenylate cyclase) ne rend probablement pas compte des effets differents de la cafeine et de la carbamazepine sur l'activite nerveuse. RESUMEN Se nan investigado los efectos, en ratas, de la administracion de una dieta rica en cafeina o en carbamazepina, mediante un estudio autorradiagrafico cuantitativo de los receptores de ade-nosina Al (marcados mediante [3H] ciclohexiladenosina, [3H] CHA) y de la ciclasa-adenilato (marcada con [3H] forskolina). Mientras que la distribucion regional de los lugares de acoplamiento de [3H] CHA y [3H] forskolina eran diferentes en algunas areas, la presencia cronica de carboamazepina y de cafeina elevaron la regulacion de ambos tipos de receptores. Los cambios de las densidades de los receptores ocurrieron en las mismas microregiones del cerebro lo que sugiere que la cafeina y la carbamazepina actuan como antagonistas en subpoblaciones semejantes de receptores de adenosina Al y de los lugares de acoplamiento de la [3H] forskolina. Por lo tanto la existencia de una interaction selectiva de estas dos drogas con distintos receptores de adenosina Al (y ciclasa-adenilato) probablemente no explica los efectos diferenciales de la cafeina y la carbamazepina sobre la actividad neuronal. ZUSAMMENFASSUNG Die Auswirkungen einer mit Coffein oder Carbamazepin an-gereicherten Diat wurden in der Ratte in einer quantitativen au-toradiographischen Studie von Adenosin-Al Rezeptoren (mark-iert mit [3H]Cyclohexyladenosin, [3H]CHA) und Adenylat Cyclase (markiert mit [3H]Forskolin) untersucht. Es konnte gezeigt werden, dass sowohl chronische Carbamazepin als auch Coffein-Diat zentrale Adenosin-Al Rezeptoren und [3H] forskolin-bindungsstellen hochregulieren. Die Veranderungen der Rezep-tordichte ereigneten sich in denselben Hirnregionen. Dieses Ergebnis legt nahe, dass Coffein und Carbamazepin als Antago-nisten an ahnlichen Untergruppen von an Adenosin Al Rezeptoren und [3H]Forskolin-Bindungsstellen wirken. Eine selektive Interaktion dieser beiden Substanzen mit unterschiedlichen Adenosin Al Rezeptoren (und Adenylat Cyclasen) erklart daher wahrscheinlich nicht die unterschiedlichen Effekte von Coffein und Carbamazepin auf die neuronale Aktivitat.

Summary: The effect of carbamazepine on adenosine receptors in vitro has been well documented, with findings from several groups showing that therapeutic doses of this drug are sufficient to inhibit binding to the major portion of adenosine receptors in brain. In this study, we describe the effects of chronic carbamazepine on central adenosine receptors from several areas of rat brain using [3H]diethylphenylxanthine ([3H]DPX) and [3H]cyclohexyladenosine ([3H]CHA) as ligands. Carbamazepine was administered to rats orally in the diet at doses of 2.25 g/kg of diet and 5.0 g/kg of diet for periods of 3 and 11 days, respectively. Carbamazepine-treated animals displayed higher levels of adenosine receptors in virtually all brain areas tested, most of which reached significance in the 11-day treatment group. Scatchard analysis revealed increases in the number of receptors. There was no change in peripheral and central type benzodiazepine receptors or β-adrenergic receptors in the carbamazepine-treated animals. Therefore, carbamazepine treatment in vivo appears to upregulate adenosine receptors, suggesting that this drug may act as an adenosine antagonist. RESUME L'effet de la carbamazepine sur les recepteurs de l'adenosine a ete bien etudie in vitro et les constatations de plusieurs groupes d'investigateurs montrent que des doses therapeutiques de ce produit sont suffisantes pour inhiber la majorite des recepteurs d'adenosine du cerveau. Cette etude decrit les effets de l'administration chronique de carbamazepine sur les recepteurs de l'adenosine de diverses aires cerebrales du rat en utilisant les (3H) DPX et (3H) CHA comme ligands. La carbamazepine a ete administree par voie orale dans l'alimentation des rats a des doses de 2,25 g/kg d'aliments et de 5,0 g/kg d'aliments pour des periodes de 3 et 11 jours. Les animaux traites par la carbamazepine ont un taux plus eleve de recepteurs de l'adenosine dans a peu pres toutes les zones cerebrales etudiees, dont la plupart a un taux atteignant la significativite statistique dans le groupe ayant ete traite 11 jours. L'analyse du scatchard montrait une augmentation du nombre de recepteurs. II n'y a pas de modification des recepteurs de type cerebral ou peripherique pour les benzodiazepines, ni des recepteurs B. adrenergiques chez les animaux traites par la carbamazepine. Le traitement par la carbamazepine in vivo, semble done hypersensibiliser les recepteurs pour l'adenosine suggerant que cette substance peut agir comme un antagoniste de l'adenosine. RESUMEN Los efectos de la carbamazepina sobre los receptores de adenosina in vitro han sido bien documentados en estudios de diversos grupos que muestran que las dosis terapeuticas de esta medicacion son suficientes para inhibir la mayor parte de los receptores de adenosina en el cerebro. En este estudio describimos los efectos de la carbamazepina cronica sobre los receptores centrales de adenosina en diversas regiones del cerebro de rata utilizando 3H DPX y 3H CHA como ligandos. La carbamazepina se administro a las ratas por via oral en sudieta habitual a dosis de 2.25 g/kg de su dieta y 5.0 g/kg de dieta durante periodos de 3 y 11 dias. Los animales tratados con carbamazepina mostraron niveles mas altos de receptores de adenosina virtualmente en todas las areas cerebrales examinadas mostrando, en su mayor parte, resultados significativos en el dia 11 del grupo tratado. Los “Scatchard analisis” han revelado incremento del numero de receptores. No se observo ningun cambio en los receptores perifericos o centrales de la benzo-diazepina o en los receptores B adrenergicos en los animales tratados con carbamazepina. Por lo tanto, el tratamiento de carbamazepina in vivo, parece que incrementa la regulacion de los receptores de adenosina, lo que sugiere que esta medicacion puede actuar como un antagonista de la adenosina. ZUSAMMENFASSUNG Die Wirkung des Carbamazepins auf die Adenosin-Rezeptoren ist in vitro durch Befunde von verschiedenen Gruppen gut dokumentiert, die gezeigt haben, das therapeutische Dosen dieses Medikaments aus-reichen, einen grosen Anteil der Adenosin-Rezeptoren des Gehirns zu inhibieren. In dieser Untersuchung beschreiben wir die Wirkungen der chronischen Carbamazepin-Anwendung auf die zentralen Adenosin-Rezeptoren in verschiedenen Gegenden des Rattenhirns; sie wurden mit (3H) DPX und (3H) CHA als Liganden durchgefuhrt. Carbamazepin wurde den Ratten oral in einer Diat mit Dosen von 2,25 g/kg Diat und 5,0g/kg wahrend 3 bis 11 Tagen verabfolgt. Die mit Carbamazepin behandelten Tiere zeigten hohere Spiegel von Adenosinrezeptoren in praktisch allen untersuchten Hirnarealen; die meisten von ihnen erreichten eine Signifikanz am 11. Behandlungstag. Scatchard-Analyse zeigte eine Vermehrung in der Anzahl der Rezeptoren. Bei den mit Carbamazepin behandelten Tieren gab es keine Veranderungen in den peripheren und zentralen Rezeptoren vom Benzodiazepin-Typ oder den B-adrenergen Rezeptoren. Carbamazepin-Behandlung in vivo scheint die Adenosin-Rezeptoren hochzuregeln und last vermuten, das dieses Medikament als Adenosin-Antagonist wirkt.