Effects of administration of SKF 38393, a D1 agonist, on methamphetamine-induced changes in shape of Zebrin bands in rat cerebellum

University of Cambridge (2004) J Physiol 555P, C58

Communications: Effects of administration of SKF 38393, a D1 agonist, on methamphetamine-induced changes in shape of Zebrin bands in rat cerebellum

Mitsuko Hamamura, Takahide Shuto, Takao Shimazoe, Yasuyuki Fukumaki and Shigenori Watanabe

Department of Pharmacology, School of Pharmaceutical Sciences, and Division of Disease Genes, Institute of Genetic Information, Center for Bio-Regulation, Kyushu University Fukuoka 812-8582 Japan

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The cerebellum is involved in emotional stress response and has parasagittal Zebrin (Aldolase C; Aldoc) bands expressed in Purkinje cells, which is thought to be a modular computing system (Brochu et al. 1990). Zebrin compartment has plasticity after external stimuli (Dusart et al. 1994; Zagrebelsky et al. 1997). We have reported by in situ hybridization study that daily methamphetamine administration (5 mg kg-1, I.P.) for 3 days into rats induced fragmentation of Aldoc mRNA stripes and lateral shift of those stripes (Hamamura M et al. 1999). To know if these shape changes of Aldoc mRNA stripes are correlated with hyper locomotive behaviour induced by methamphetamine injections, we measured Aldoc mRNA in rats injected with a D1 receptor agonist SKF38393 (1 mg kg-1, I.P.) for 1 week after prior injections (once 3 days for 2 weeks) of the methamphetamine (1 mg kg-1, I.P.), whose treatment induced loss of hyper locomotion (Shuto et al. 2003). The rats were killed humanely.

The rats with the five injections of methamphetamine showed fragmentation of Aldoc mRNA stripe in the lobules VII and VIII. In addition, in the rats with the same repeated injections followed by the seven daily SKF38393 injections the number of stripes of Aldoc mRNA was not significantly different from those with repeated methamphetamine injections. On the other hand the shift of horizontal location of Aldoc mRNA stripes from the meridian in rats with repeated methamphetamine administration (n = 4 for each) was significantly different from either that in the saline control or that in the rats with methamphetamine plus SKF38393 treatment (P < 0.05, n = 4 for each, Wilcoxson’s signed rank test). Since the SKF treatment rescued the horizontal shift of the Aldoc mRNA stripes induced by repeated methamphetamine injections, we conclude that the horizontal location change in Aldoc mRNA stripe but not the fragmentation is well correlated with behaviour in amphetamine psychosis.



Where applicable, experiments conform with Society ethical requirements.

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