title: Antipsychotics improve Delta9-tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice.
abstract: 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.
authors.affiliation: Department of Psychiatry, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sano
authors.forename: Ayumi
authors.initials: A
authors.lastname: Ogata
authors.forename: Ai
authors.initials: A
authors.lastname: Mizuki
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: 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
chemical_list: D014150:Antipsychotic Agents; D010880:Piperidines; D011720:Pyrazoles; D013759:Dronabinol; D006220:Haloperidol; D018967:Risperidone; D000077285:Rimonabant; D004298:Dopamine