Egashira Nobuaki, Matsuda Tomomi, Koushi Emi, Mishima Kenichi, Iwasaki Katsunori, Shoyama Yukihiro, Fujiwara Michihiro
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka, University, 8-19-1, Nanakuma, Fukuoka 814-0180, Japan.
Eur J Pharmacol. 2006 Nov 21;550(1-3):117-22. doi: 10.1016/j.ejphar.2006.08.051. Epub 2006 Sep 6.
The present study investigated the involvement of 5-hydroxytryptamine(1A) (5-HT(1A)) receptors in Delta(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.
本研究调查了5-羟色胺（1A）（5-HT（1A））受体在δ9-四氢大麻酚（THC）诱导的小鼠僵住样不动状态中的作用。THC（10毫克/千克，腹腔注射）诱导了僵住样不动状态，但在转棒试验中对运动协调性没有影响。选择性大麻素CB（1）受体拮抗剂利莫那班（3毫克/千克，腹腔注射）完全拮抗了THC诱导的僵住样不动状态。5-HT（1A）/5-HT（7）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT；0.3和1毫克/千克，腹腔注射）以及5-HT（1A）受体部分激动剂丁螺环酮（0.06和0.1毫克/千克，腹腔注射）抑制了这种THC诱导的僵住样不动状态。此外，选择性5-HT（1A）受体拮抗剂N-[2-[4-（2-甲氧基苯基）-1-哌嗪基]乙基]-N-（2-吡啶基）环己烷甲酰胺二盐酸盐（WAY100635；0.3或1毫克/千克，腹腔注射）逆转了8-OH-DPAT（1毫克/千克）或丁螺环酮（0.06毫克/千克）对THC诱导的僵住样不动状态的抑制作用。相比之下，选择性5-HT（7）受体拮抗剂（R）-3-[2-[2-（4-甲基哌啶-1-基）乙基]吡咯烷-1-磺酰基]苯酚盐酸盐（SB269970）对8-OH-DPAT的这种抑制作用没有影响。另一方面，WAY100635（0.3和1毫克/千克，腹腔注射）增强了THC（6毫克/千克，腹腔注射）诱导的僵住样不动状态。这些发现表明，5-HT（1A）受体参与了THC诱导的僵住样不动状态。
