The effect of Delta9-tetrahydrocannabinol on sensorimotor gating in socially isolated rats.
Rearing rats in isolation produces behavioural and neurochemical alterations similar to those observed in schizophrenia. Cannabinoids have also been implicated in inducing psychotic symptoms. In this study, we investigate the effect of the major psychoactive constituent of cannabis and partial cannabinoid CB(1) receptor agonist Delta(9)-tetrahydrocannabinol (THC) on prepulse inhibition (%PPI) of the acoustic startle reflex and on habituation in socially isolated and grouped rats. Deficits in %PPI are reminiscent of sensorimotor gating deficits observed in psychoses. Male Sprague-Dawley rat pups (21 days old) were housed in either single cages (isolated) or in group cages of six per cage (grouped). Eight weeks later the effect of vehicle, THC and the CB(1) receptor antagonist SR 141716 on %PPI was tested. Vehicle treated isolated rats exhibited significantly reduced PPI compared with grouped rats. Isolated rats treated with THC had significantly lower %PPI than vehicle treated groups. This further decrease of %PPI by THC was reversed by pre-treatment with SR 141716, indicating that this effect was mediated by CB(1) receptors. THC had no significant effect on %PPI in grouped rats. SR 141716 had no significant effect on %PPI in either grouped or isolated rats. Habituation did not significantly alter in any treatment group in any treatment group. These results suggest that THC produces significant decreases in sensorimotor gating in rats with already dysfunctional sensorimotor gating processes, but not in normal rats. The lack of effect of SR 141716 in either grouped or isolated rats suggests that normal endocannabinoid function is not critical in sensorimotor gating processes.
Malone
Daniel Thomas
DT
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University, Parkville 3052, Vic., Australia. dan.malone@vcp.monash.edu.au
Taylor
David Alan
DA
D000161:Acoustic Stimulation / Q000379:methods; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D063387:Cannabinoid Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D007266:Inhibition, Psychological; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D000077285:Rimonabant; D012934:Social Isolation / Q000523:psychology*
D063387:Cannabinoid Receptor Antagonists; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D013759:Dronabinol; D000077285:Rimonabant