The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats.
There is evidence that indicates that tonic activation of cannabinoid CB1 receptors plays a role in extinction/reinstatement of cocaine seeking-behavior but is not involved in the maintenance of cocaine self-administration. To further explore the importance of other endocannabinoid-related receptors in an animal model of cocaine addiction, the present paper examines cannabinoid CB2 receptor antagonist N-((1S)-endo-1,3,3-trimethylbicyclo(2.2.1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and the transient receptor potential vanilloid type-1 (TRPV1) receptor antagonist N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) on intravenous (i.v.) cocaine self-administration and extinction/reinstatement of cocaine-seeking behavior in rats. For comparison and reference purposes, the effect of the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251) was also examined. Moreover, for comparison effects of those drugs on operant lever responding for artificial (cocaine) vs. natural (food) reward, food self-administration was also evaluated. Our findings show that AM251 (1-3mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.3-1mg/kg) did not affect cocaine self-administration. However, AM251 (0.1-1mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.1-1mg/kg) decreased cocaine-induced reinstatement of cocaine-seeking behavior, and AM251 (0.3-1mg/kg) decreased cue-induced reinstatement. Moreover, AM251 (3mg/kg), SR144528 (0.1-1mg/kg) and SB366791 (0.1-1mg/kg) slightly decreased food self-administration behavior, but only AM251 (3mg/kg) reduced food reward. In conclusion, our results indicate for the first time, that tonic activation of CB2 or TRPV1 receptors is involved in cocaine-induced reinstatement of cocaine-seeking behavior, but their activity is not necessary for the rewarding effect of this psychostimulant. In contrast to CB1 receptors, neither CB2 nor TRPV1 receptors play a role in cue-induced reinstatement of cocaine-seeking behavior.
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland. adamczyk@if-pan.krakow.pl
Przemysław
P
Adamczyk
Joanna
J
Miszkiel
Andrew C
AC
McCreary
Małgorzata
M
Filip
Mariusz
M
Papp
Edmund
E
Przegaliński
D000704:Analysis of Variance; D000813:Anilides / Q000627:therapeutic use; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000209:etiology; D001892:Camphanes / Q000627:therapeutic use; D002934:Cinnamates / Q000627:therapeutic use; D019970:Cocaine-Related Disorders / Q000150:complications / Q000188:drug therapy*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects; D005502:Food; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010880:Piperidines / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors*
D000813:Anilides; D001892:Camphanes; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; C103505:AM 251