Blockade of cannabinoid (CB1) receptors by 141716 selectively antagonizes drug-induced reinstatement of exploratory behaviour in gerbils.
BACKGROUND
A cannabinoid hypothesis of schizophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system.


OBJECTIVE
The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms.


METHODS
Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor.


RESULTS
SR 141716 (0.3-3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils.


CONCLUSIONS
The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.
Sanofi Recherche, Montpellier, France. martine.poncelet@sanofi.com
M
M
Poncelet
M C
MC
Barnouin
J C
JC
Brelière
G
G
Le Fur
P
P
Soubrié
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002186:Cannabinoids / Q000037:antagonists & inhibitors*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects*; D005849:Gerbillinae; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009294:Narcotics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors*; D000077285:Rimonabant
D014150:Antipsychotic Agents; D002186:Cannabinoids; D000697:Central Nervous System Stimulants; D009294:Narcotics; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D000077285:Rimonabant