Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice.
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.
Ago
Yukio
Y
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.
Nakamura
Shigeo
S
Kajita
Naoko
N
Uda
Misato
M
Hashimoto
Hitoshi
H
Baba
Akemichi
A
Matsuda
Toshio
T
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D051379:Mice; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D016713:Ritanserin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D012702:Serotonin Antagonists; D016713:Ritanserin; D008694:Methamphetamine