TY - JOUR
T1 - Antipsychotics improve Δ9-tetrahydrocannabinol-induced impairment of the prepulse inhibition of the startle reflex in mice
AU - Nagai, Hiroshi
AU - Egashira, Nobuaki
AU - Sano, Kazunori
AU - Ogata, Ayumi
AU - Mizuki, Ai
AU - Mishima, Kenichi
AU - Iwasaki, Katsunori
AU - Shoyama, Yukihiro
AU - Nishimura, Ryoji
AU - Fujiwara, Michihiro
N1 - Funding Information:
Part of this study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (No. 18591318). The authors are grateful to Sanofi Synthelabo and Janssen Research Foundation for the gift of SR141716 and risperidone used in this study.
PY - 2006/6
Y1 - 2006/6
N2 - 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 Δ9-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.
AB - 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 Δ9-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.
UR - http://www.scopus.com/inward/record.url?scp=33746282857&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746282857&partnerID=8YFLogxK
U2 - 10.1016/j.pbb.2006.05.018
DO - 10.1016/j.pbb.2006.05.018
M3 - Article
C2 - 16820196
AN - SCOPUS:33746282857
SN - 0091-3057
VL - 84
SP - 330
EP - 336
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
IS - 2
ER -