Involvement of 5-hydroxytryptamine 1A receptors in Δ 9-tetrahydrocannabinol-induced catalepsy-like immobilization in mice

Abstract

The present study investigated the involvement of 5-hydroxytryptamine 1A (5-HT 1A) receptors in Δ 9-tetrahydrocannabinol (THC)-induced catalepsy-like immobilization in mice. THC (10 mg/kg, i.p.) induced catalepsy-like immobilization but had no effect on motor coordination in the rota-rod test. The selective cannabinoid CB 1 receptor antagonist rimonabant (3 mg/kg, i.p.) completely antagonized THC-induced catalepsy-like immobilization. The 5-HT 1A/5-HT 7 receptor agonist 8-hydroxy-2-(di- n-propylamino) tetralin (8-OH-DPAT; 0.3 and 1 mg/kg, i.p.) and 5-HT 1A receptor partial agonist buspirone (0.06 and 0.1 mg/kg, i.p.) inhibited this THC-induced catalepsy-like immobilization. Moreover, the selective 5-HT 1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]- N-(2-pyridinyl) cyclohezane carboxamide dihydrochloride (WAY100635; 0.3 or 1 mg/kg, i.p.) reversed the inhibition of THC-induced catalepsy-like immobilization by 8-OH-DPAT (1 mg/kg) or buspirone (0.06 mg/kg). In contrast, the selective 5-HT 7 receptor antagonist ( R)-3-[2-[2-(4-methylpiperidin-1-yl)ethyl]pyrrolidine-1-sulfonyl]phenol hydrochloride (SB269970) had no effect on this inhibitory effect of 8-OH-DPAT. On the other hand, WAY100635 (0.3 and 1 mg/kg, i.p.) enhanced the catalepsy-like immobilization induced by THC (6 mg/kg, i.p.). These findings suggest that the 5-HT 1A receptors are involved in THC-induced catalepsy-like immobilization.