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J Pharmacol Exp Ther. 1993 Dec;267(3):1538-43.

Cardiovascular, thermal and behavioral sensitization to methamphetamine in freely moving rats.

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Department of Legal Medicine, Yamaguchi University School of Medicine, Ube, Japan.


Mean arterial blood pressure (MAP), heart rate (HR), body temperature (BT) and locomotive activity (LA) were measured simultaneously after i.p. or i.c.v. injection of methamphetamine (MAH) using a biotelemetric system. The system enabled us to observe the parameters in freely moving rats under minimum stress. MAH (1 mg/kg) given by i.p. injection significantly increased MAP, HR, BT and LA, as compared with the saline-control. MAH (5, 50 micrograms) administered by i.c.v. injection stimulated responses of HR, BT and LA. After the i.p. injections of MAH (1 mg/kg) on days 1, 4, 8, 11 and 15, MAH was administered either through i.p. (1 mg/kg) or i.c.v. (50 micrograms) route on day 18. In addition to the LA sensitization induced by i.p. and i.c.v. administration of MAH, it was found for the first time, to our knowledge, that the repeated i.p. injections potentiated the responses of MAP and BT to the subsequent injection of MAH through i.p., but not i.c.v., route. The latter finding suggests that the sensitization, produced by the repeated i.p. injections, affected responses that MAH induced either peripherally or centrally through a peripheral humoral factor or an afferent nervous system.

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