title: Long-lasting increase in [³H]CP55,940 binding to CB1 receptors following cocaine self-administration and its withdrawal in rats.
abstract: The present work has aimed on the neuroadaptive changes in CB1 receptor density that are evoked by self-administered cocaine use and subsequent withdrawal in rats. We employed a quantitative autoradiographic analysis using labeled [³H]CP55,940, a CB1 receptor agonist. To distinguish the passive pharmacological effects of cocaine from those related to motivation and the cognitive processes evoked by active cocaine self-administration, the "yoked" procedure was used. Our results demonstrate that repeated cocaine administration over 14 days induced up-regulation of CB1 receptors in the cortical and subcortical brain areas of animals who received cocaine, whether the cocaine was actively self-administered or received passively (the "yoked" control group) and that the neuroadaptation of CB1 receptors persisted after the 10-day extinction phase. On the other hand, we found that only self-administering rats showed CB1 receptor up-regulation in numerous brain areas, which suggests that these structures may be directly linked to CB1 receptor control over motivational and cognitive processes. Moreover, the observed increase in [³H]CP55,940 binding in these brain areas likely indicates long-lasting neurobiological adaptations resulting from chronic cocaine self-administration. In conclusion, we demonstrated that chronic cocaine self-administration leads to increased CB1 receptor levels in numerous brain areas and that this neuroadaptation is maintained over a long-lasting extinction period.
authors.affiliation: Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland. adamczyk@if-pan.krakow.pl
authors.forename: Przemysław
authors.initials: P
authors.lastname: Adamczyk
authors.forename: Agata
authors.initials: A
authors.lastname: Faron-Górecka
authors.forename: Maciej
authors.initials: M
authors.lastname: Kuśmider
authors.forename: Marta
authors.initials: M
authors.lastname: Dziedzicka-Wasylewska
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Filip
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002186:Cannabinoids / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage*; D003511:Cyclohexanols / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D012646:Self Administration; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002186:Cannabinoids; D003511:Cyclohexanols; D018765:Dopamine Uptake Inhibitors; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D003042:Cocaine