Dopamine neurotransmission is involved in the attenuating effects of 5-HT₃ receptor antagonist MDL 72222 on acute methamphetamine-induced locomotor hyperactivity in mice

다국어 초록 (Multilingual Abstract)

<P>We have previously shown that 5-HT<SUB>3</SUB> 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-HT<SUB>3</SUB> receptor antagonist, on acute MAP-induced locomotor hyperactivity. For this, we examined alterations of dopamine (DA) in the form of D<SUB>1</SUB> receptor, D<SUB>2</SUB> receptor, and dopamine transporter (DAT) binding labeled with [<SUP>3</SUP>H]SCH23390 for D<SUB>1</SUB>, [<SUP>3</SUP>H]raclopride for D<SUB>2</SUB>, and [<SUP>3</SUP>H]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 D<SUB>1</SUB> receptor, D<SUB>2</SUB> 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-HT<SUB>3</SUB> receptor antagonist MDL 72222 on acute MAP-induced locomotor hyperactivity in mice. Synapse 62:8–13, 2008. © 2007 Wiley-Liss, Inc.</P>