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Ritanserin reverses repeated methamphetamine‐induced behavioral and neurochemical sensitization in mice
Author(s) -
Ago Yukio,
Nakamura Shigeo,
Kajita Naoko,
Uda Misato,
Hashimoto Hitoshi,
Baba Akemichi,
Matsuda Toshio
Publication year - 2007
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.20421
Subject(s) - ritanserin , neurochemical , sensitization , meth , methamphetamine , prefrontal cortex , pharmacology , chemistry , antagonist , neuroscience , psychology , medicine , receptor antagonist , receptor , cognition , monomer , organic chemistry , acrylate , polymer
Chronic administration of methamphetamine (METH) elicits progressive enhancement of locomotor activity known as behavioral sensitization. We have recently shown that chronic METH enhanced METH challenge‐induced increase in 5‐HT levels in the prefrontal cortex and that 5‐HT 1A receptor activation attenuated this neurochemical sensitization as well as behavioral sensitization. This study examined whether the nonselective 5‐HT 2 receptor antagonist, ritanserin affects METH‐induced behavioral and neurochemical sensitization in mice. Ritanserin at doses of 1 and 3 mg/kg inhibited the development and expression of METH‐induced behavioral sensitization in a dose‐dependent manner. Furthermore, chronic administration of ritanserin for a week attenuated the maintenance of behavioral sensitization, indicating the improvement of established behavioral sensitization. Microdialysis analysis showed that chronic ritanserin inhibited the neurochemical sensitization that chronic METH enhanced METH challenge‐induced increase in extracellular 5‐HT levels in the prefrontal cortex. Furthermore, acute ritanserin inhibited METH challenge‐induced increase in extracellular 5‐HT but not DA levels in the prefrontal cortex. These results suggest that 5‐HT 2 receptors are involved in METH‐induced hyperactivity and behavioral sensitization in mice. Synapse 61:757–763, 2007. © 2007 Wiley‐Liss, Inc.