18377702

pubmed:Citation

7

Cannabinoids, in contrast to typical drugs of abuse, have been shown to exert complex effects on behavioural reinforcement and psychomotor function. We have shown that cannabinoid agonists lack reinforcing/rewarding properties in the intracranial self-stimulation (ICSS) paradigm and that the CB1 receptor (CB1R) agonist WIN55,212-2 attenuates the reward-facilitating actions of cocaine. We sought to determine the effects of the endocannabinoid neurotransmission enhancer AM-404 (1, 3, 10, 30 mg/kg) on the changes in ICSS threshold and locomotion elicited by cocaine and extend the study of the effects of WIN55,212-2 (0.3, 1, 3 mg/kg) on cocaine-induced hyperlocomotion. AM-404 did not exhibit reward-facilitating properties, and actually increased self-stimulation threshold at the highest dose. Cocaine significantly reduced self-stimulation threshold, without altering maximal rates of responding. AM-404 (10 mg/kg) attenuated this action of cocaine, an effect which was reversed by pretreatment with the selective CB1R antagonist SR141716A. WIN55,212-2 decreased locomotion at the two highest doses, an effect that was blocked by SR141716A; AM-404 had no effect on locomotion. Cocaine caused a significant, dose-dependent increase in locomotion, which was reduced by WIN55,212-2 and AM-404. SR141716A blocked the effects of WIN55,212-2 and AM-404 on cocaine-induced hyperlocomotion. SR141716A alone had no effect on ICSS threshold or locomotion. These results indicate that cannabinoids may interfere with brain reward systems responsible for the expression of acute reinforcing/rewarding properties of cocaine, and provide further evidence that the cannabinoid system could be explored as a potential drug discovery target for the treatment of psychostimulant addiction and pathological states associated with psychomotor overexcitability.

http://linkedlifedata.com/resource/pubmed/journal/9815893

http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids, http://linkedlifedata.com/resource/pubmed/chemical/Benzoxazines, http://linkedlifedata.com/resource/pubmed/chemical/Central Nervous System Stimulants, http://linkedlifedata.com/resource/pubmed/chemical/Cocaine, http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids, http://linkedlifedata.com/resource/pubmed/chemical/Morpholines, http://linkedlifedata.com/resource/pubmed/chemical/N-(4-hydroxyphenyl)arachidonylamide, http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes, http://linkedlifedata.com/resource/pubmed/chemical/Piperidines, http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles, http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB1, http://linkedlifedata.com/resource/pubmed/chemical/Win 55212-2, http://linkedlifedata.com/resource/pubmed/chemical/rimonabant

Nov

pubmed-author:NomikosGeorge GGG, pubmed-author:PanagisGeorgeG, pubmed-author:StamatopoulouFygaleiaF, pubmed-author:VlachouStylianiS

11

Y

pubmed-meshheading:18377702-Animals, pubmed-meshheading:18377702-Arachidonic Acids, pubmed-meshheading:18377702-Benzoxazines, pubmed-meshheading:18377702-Central Nervous System Stimulants, pubmed-meshheading:18377702-Cocaine, pubmed-meshheading:18377702-Conditioning, Operant, pubmed-meshheading:18377702-Endocannabinoids, pubmed-meshheading:18377702-Male, pubmed-meshheading:18377702-Morpholines, pubmed-meshheading:18377702-Motor Activity, pubmed-meshheading:18377702-Naphthalenes, pubmed-meshheading:18377702-Piperidines, pubmed-meshheading:18377702-Pyrazoles, pubmed-meshheading:18377702-Rats, pubmed-meshheading:18377702-Rats, Sprague-Dawley, pubmed-meshheading:18377702-Receptor, Cannabinoid, CB1, pubmed-meshheading:18377702-Reward, pubmed-meshheading:18377702-Self Stimulation, pubmed-meshheading:18377702-Synaptic Transmission

Enhancement of endocannabinoid neurotransmission through CB1 cannabinoid receptors counteracts the reinforcing and psychostimulant effects of cocaine.

Journal Article, Research Support, Non-U.S. Gov't