Involvement of 5-HT receptors in the development and expression of methamphetamine-induced behavioral sensitization: 5-HT receptor channel and binding study.
Methamphetamine (MAP) is one of the most commonly abused drugs in Asia, and previous studies suggest that serotonin 3 receptors (5-HT(3)) are involved in MAP-induced locomotion and reward. However, little is known about the role of 5-HT(3) receptors in MAP-induced behavioral sensitization. Here, we measured the effects of MDL 72222, a 5-HT(3) antagonist, and SR 57227 A, a 5-HT(3) agonist, on the development and expression of MAP-induced behavioral sensitization, and alternations of 5-HT(3) receptor binding labeled with the 5-HT(3)-selective antagonist, [(3)H]GR65630, in mice. In addition, we investigated the effects of MAP on 5-HT(3A) receptor channel activity in Xenopus laevis oocytes expressing 5-HT(3A) receptors. We found that MDL 72222 attenuated both the development and expression of behavioral sensitization to MAP (1.0 mg/kg, i.p.), and that this attenuating effect of MDL 72222 was reversed by pre-treatment with SR 57227 A. In oocytes expressing 5-HT(3A) receptor, MAP exhibited a dual modulation of 5-HT(3A) receptor channel activity, i.e. pre-treatment with a low dose of MAP (0.1 microm) enhanced 5-HT-induced inward peak current (I(5-HT)) but a high dose of MAP (100 microm) inhibited I(5-HT). The acute administration of MDL 72222 with MAP decreased [(3)H]GR65630 binding versus MAP alone in the mouse striatum. Our results suggest that MDL 72222 attenuates MAP-induced behavioral sensitization via 5-HT(3) receptors in the caudate putamen, and that 5-HT(3) receptor antagonists like MDL 72222 have potential as novel anti-psychotic agents for the treatment of MAP dependence and psychosis.
Yoo
Ji-Hoon
JH
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Cho
Jae-Han
JH
Yu
Hyun-Sook
HS
Lee
Kwang-Wook
KW
Lee
Byung-Hwan
BH
Jeong
Sang Min
SM
Nah
Seung-Yeol
SY
Kim
Hyoung-Chun
HC
Lee
Seok-Yong
SY
Jang
Choon-Gon
CG
D000465:Algorithms; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects; D009865:Oocytes / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D018075:RNA, Complementary / Q000096:biosynthesis; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology; D014982:Xenopus laevis
D018765:Dopamine Uptake Inhibitors; D007093:Imidazoles; D007211:Indoles; D010880:Piperidines; D018075:RNA, Complementary; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; C059068:GR 65630; D008694:Methamphetamine; C042253:bemesetron; C083009:4-amino-1-(6-chloro-2-pyridyl)piperidine hydrochloride