Ritanserin reverses repeated methamphetamine-induced behavioral and neurochemical sensitization in mice. 2007

Yukio Ago, and Shigeo Nakamura, and Naoko Kajita, and Misato Uda, and Hitoshi Hashimoto, and Akemichi Baba, and Toshio Matsuda
Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008694 Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D009043 Motor Activity Body movements of a human or an animal as a behavioral phenomenon. Activities, Motor,Activity, Motor,Motor Activities
D001923 Brain Chemistry Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states. Chemistry, Brain,Brain Chemistries,Chemistries, Brain
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D000697 Central Nervous System Stimulants A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. Analeptic,Analeptic Agent,Analeptic Drug,Analeptics,CNS Stimulant,CNS Stimulants,Central Nervous System Stimulant,Central Stimulant,Analeptic Agents,Analeptic Drugs,Central Stimulants,Agent, Analeptic,Agents, Analeptic,Drug, Analeptic,Drugs, Analeptic,Stimulant, CNS,Stimulant, Central,Stimulants, CNS,Stimulants, Central
D000704 Analysis of Variance A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. ANOVA,Analysis, Variance,Variance Analysis,Analyses, Variance,Variance Analyses
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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