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Dopamine neurotransmission is involved in the attenuating effects of 5‐HT 3 receptor antagonist MDL 72222 on acute methamphetamine‐induced locomotor hyperactivity in mice
Author(s) -
Yoo JiHoon,
Nam YunSun,
Lee SeokYong,
Jang ChoonGon
Publication year - 2008
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20461
Subject(s) - dopamine transporter , raclopride , dopamine , receptor antagonist , dopaminergic , pharmacology , methamphetamine , receptor , dopamine receptor d2 , dopamine plasma membrane transport proteins , dopamine receptor , 5 ht receptor , biology , antagonist , chemistry , medicine , endocrinology , serotonin , biochemistry
Abstract We have previously shown that 5‐HT 3 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 3 receptor antagonist, on acute MAP‐induced locomotor hyperactivity. For this, we examined alterations of dopamine (DA) in the form of D 1 receptor, D 2 receptor, and dopamine transporter (DAT) binding labeled with [ 3 H]SCH23390 for D 1 , [ 3 H]raclopride for D 2 , and [ 3 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 1 receptor, D 2 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 3 receptor antagonist MDL 72222 on acute MAP‐induced locomotor hyperactivity in mice. Synapse 62:8–13, 2008. © 2007 Wiley‐Liss, Inc.