Research article summary (published 30 Mar 2008):

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

Full Abstract

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.

Author information

Author/s: Vlachou, Styliani (S); Stamatopoulou, Fygaleia (F); Nomikos, George G (GG); Panagis, George (G);

Affiliation: Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, Rethymnon, Crete, Greece.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP) (Int J Neuropsychopharmacol), published in England. (Language: eng)

Reference: 2008-Nov; vol 11 (issue 7) : pp 905-23

Dates: Created 2008/09/30; Completed 2008/12/08;

PMID: 18377702, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Arachidonic Acids - pharmacology Benzoxazines - pharmacology Central Nervous System Stimulants - antagonists & inhibitors; pharmacology Cocaine - antagonists & inhibitors; pharmacology Conditioning, Operant - drug effects Endocannabinoids - physiology Male Morpholines - pharmacology Motor Activity - drug effects

Motor Activity - drug effects Naphthalenes - pharmacology Piperidines - pharmacology Pyrazoles - pharmacology Rats Rats, Sprague-Dawley Receptor, Cannabinoid, CB1 - agonists; antagonists & inhibitors; drug effects Reward Self Stimulation Synaptic Transmission - drug effects; physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Arachidonic Acids (0) ; Benzoxazines (0) ; Central Nervous System Stimulants (0) ; Endocannabinoids (0) ; Morpholines (0) ; N-(4-hydroxyphenyl)arachidonylamide (0) ; Naphthalenes (0) ; Piperidines (0) ; Pyrazoles (0) ; Receptor, Cannabinoid, CB1 (0) ; Win 55212-2 (134959-51-6) ; rimonabant (158681-13-1) ; Cocaine (50-36-2)

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