Delta(9)-tetrahydrocannabinol prolongs the immobility time in the mouse forced swim test: involvement of cannabinoid CB(1) receptor and serotonergic system.
In the present study, we investigated the effect of Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive component of marijuana, on immobility time during the forced swim test. THC (2 and 6 mg/kg, i.p.) significantly prolonged the immobility time. In addition, THC at the same doses did not significantly affect locomotor activity in the open-field test. The selective cannabinoid CB(1) receptor antagonist rimonabant (3 mg/kg, i.p.) significantly reduced the enhancement of immobility by THC (6 mg/kg). Similarly, the selective serotonin (5-HT) reuptake inhibitor (SSRI) citalopram (10 mg/kg, i.p.) and 5-HT(1A/7) receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT, 0.3 mg/kg, i.p.) significantly reduced this THC-induced effect. Moreover, the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide dihydrochloride (WAY100635, 1 mg/kg, i.p.) and the postsynaptic 5-HT(1A) receptor antagonist MM-77 (0.1 mg/kg, i.p.) reversed this reduction effect of 8-OH-DPAT (0.3 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 reduction effect of 8-OH-DPAT. WAY100635 (1 mg/kg) also reversed the reduction effect of citalopram (10 mg/kg). These findings suggest that the 5-HT(1A) receptors are involved in THC-induced enhancement of immobility.
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Nobuaki
N
Egashira
Tomomi
T
Matsuda
Emi
E
Koushi
Fuminori
F
Higashihara
Kenichi
K
Mishima
Shozo
S
Chidori
Nobuyoshi
N
Hasebe
Katsunori
K
Iwasaki
Ryoji
R
Nishimura
Ryozo
R
Oishi
Michihiro
M
Fujiwara
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects* / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D000077285:Rimonabant; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013388:Succinimides / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013550:Swimming
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015283:Citalopram; D013759:Dronabinol; D010636:Phenols; D010879:Piperazines; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D011725:Pyridines; D043884:Receptor, Cannabinoid, CB1; D044282:Receptor, Serotonin, 5-HT1A; D011985:Receptors, Serotonin; D000077285:Rimonabant; D012701:Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; D013388:Succinimides; D013449:Sulfonamides; C413583:MM 77; C404922:SB 269970; C104425:serotonin 7 receptor; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide