Antipsychotics improve Delta9-tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice.
Recently, cannabinoid receptor agonists have been reported to impair prepulse inhibition (PPI) of the startle reflex. In the current study, we examined the effect of Delta9-tetrahydrocannabinol (THC), the principal psychoactive component of cannabis, on the PPI, and found that THC (10 mg/kg, i.p.) impaired the PPI concomitant with a decrease in the startle response. Antipsychotics such as haloperidol (0.3 mg/kg, i.p.) and risperidone (0.1 mg/kg, i.p.), which are potent dopamine D2 receptor antagonists, and SR141716 (10 mg/kg, i.p.), a CB1 cannabinoid receptor antagonist, reversed these THC-induced PPI deficits. Moreover, THC (10 mg/kg) increased dopamine (DA) release in the nucleus accumbens but not medial prefrontal cortex over a 50-100-min period (time of PPI test) after treatment, and SR141716 (10 mg/kg) reversed this increase in DA release induced by THC. These results suggest that dopaminergic hyperfunction in the nucleus accumbens may be involved in THC-induced PPI deficits.
Nagai
Hiroshi
H
Department of Psychiatry, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
Egashira
Nobuaki
N
Sano
Kazunori
K
Ogata
Ayumi
A
Mizuki
Ai
A
Mishima
Kenichi
K
Iwasaki
Katsunori
K
Shoyama
Yukihiro
Y
Nishimura
Ryoji
R
Fujiwara
Michihiro
M
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007266:Inhibition, Psychological; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D013216:Reflex, Startle / Q000187:drug effects*; D000077285:Rimonabant; D018967:Risperidone / Q000494:pharmacology; D045442:Rotarod Performance Test
D014150:Antipsychotic Agents; D010880:Piperidines; D011720:Pyrazoles; D013759:Dronabinol; D006220:Haloperidol; D018967:Risperidone; D000077285:Rimonabant; D004298:Dopamine