Dopamine neurotransmission is involved in the attenuating effects of 5-HT3 receptor antagonist MDL 72222 on acute methamphetamine-induced locomotor hyperactivity in mice.
We have previously shown that 5-HT3 receptors are involved in the development and expression of methamphetamine (MAP)-induced locomotor sensitization in mice. In the present study, we further examined whether the dopaminergic system is involved in the attenuating effects of MDL 72222, a 5-HT3 receptor antagonist, on acute MAP-induced locomotor hyperactivity. For this, we examined alterations of dopamine (DA) in the form of D1 receptor, D2 receptor, and dopamine transporter (DAT) binding labeled with [3H]SCH23390 for D1, [3H]raclopride for D2, and [3H]mazindol for DAT binding in the mouse brains with acute MAP exposure or pretreatment of MDL 72222 with MAP. No significant differences were detected in the D1 receptor, D2 receptor, or DAT binding between any of the groups studied. Interestingly, we found increased DA levels in the striatum following acute MAP exposure; these increased levels were reversed by pretreatment with MDL 72222, but did not affect 5-HT levels in the dorsal raphe. Overall, our results suggest that dopamine neurotransmission plays an important role in the attenuating effects of 5-HT3 receptor antagonist MDL 72222 on acute MAP-induced locomotor hyperactivity in mice.
Yoo
Ji-Hoon
JH
Department of Pharmacology, College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
Nam
Yun-Sun
YS
Lee
Seok-Yong
SY
Jang
Choon-Gon
CG
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014326:Tropanes / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014326:Tropanes; D008694:Methamphetamine; C042253:bemesetron; D004298:Dopamine