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- Title
Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice.
- Authors
Ago, Yukio; Nakamura, Shigeo; Kajita, Naoko; Uda, Misato; Hashimoto, Hitoshi; Baba, Akemichi; Matsuda, Toshio
- Abstract
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-HT1A receptor activation attenuated this neurochemical sensitization as well as behavioral sensitization. This study examined whether the nonselective 5-HT2 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-HT2 receptors are involved in METH-induced hyperactivity and behavioral sensitization in mice. Synapse 61:757-763, 2007. © 2007 Wiley-Liss, Inc.
- Publication
Synapse, 2007, Vol 61, Issue 9, p757
- ISSN
0887-4476
- Publication type
Article
- DOI
10.1002/syn.20421