Augmentation of Regional Cerebral Blood Flow Response by Repeated Administration of Methamphetamine in Rat / 대한정신약물학회지

OBJECTIVES: It was aimed to observe the regional cerebral blood flow (rCBF) response on methamphetamine challenge test in rats which were subjected to repeated administration of methamphetamine, and to investigate the mechanism(s) of changes in rCBF response in relation to the dopaminergic receptors and cyclic AMP. METHODS: Male Sprague-Dawley rats received daily injections of methamphetamine (0.3 mg/kg, i.p.) for 10 days, and were then allowed a 4-day drug-free period. Naive and methamphetamine-pretreated rats were challenged with topical application of methamphetamine on the surface of parietal cortex through a cranial window. The changes in rCBF were measured by laser-Doppler flowmetry. RESULTS: Acute topical application of methamphetamine dose-dependently increased rCBF with little effect on mean arterial blood pressure. The methamphetamine-induced increases in rCBF were significantly blocked by SCH23390, a D1-like receptor antagonist, but not by sulpiride, a D2-like receptor antagonist. Repeated administration of methamphetamine induced progressive augmentation of rCBF in response to the challenge of methamphetamine. Repeated administration of methamphetamine in combination with SKF38393, a D1-like receptor agonist, as well as with SCH23390 significantly attenuated the development of augmentation of rCBF response to methamphetamine. The augmentation of rCBF response was markedly inhibited by pretreatment with 2',3'-dideoxyadenosine, a specific adenylyl cyclase inhibitor, and Rp-cAMPS, a protein kinase A inhibitor, respectively. CONCLUSION: Based on these results, it is suggested that repeated administration of methamphetamine induces an augmentation of rCBF in response to the challenge of methamphetamine, and that D1-like receptor-mediated cyclic AMP plays a critical role in the development of augmentation of methamphetamine-induced rCBF response.

Effect of 5-HT2c Receptor Modulation on the m-Chlorophenlpiperazine-Induced Hypoactivity / 대한정신약물학회지

It was aimed to investigate the effect of 5-HT2C receptor modulation on the rat behavioral responses induced by 1-(m-chlorophenyl) piperazine(mCPP), a major metabolite of trazodone. The animal activities(ambulation, stereotypy and total activity) were measured for 3 hours following mCPP administration, using an animal activity meter which accumulates the frequency of light beam interruption. mCPP(1-10 mg / kg, i.p.) induced dose-dependent decreases in ambulation and stereotypy, consequently leading to hypoactivity. The hypoactivity induced by mCPP(1mg / kg, i.p.) was significantly inhibited by pretreatment with mianserin(1mg / kg, i.p.), an antagonist with high affinity for 5-HT2C receptor, whereas pretreatment with 5-HT2 antagonists, ketanserin and ritanserin(1mg / kg, i.p., respectively) was without effect. Furthermore, long-term pretreatment with imipramine(10mg / kg, i.p., b.i.d. for 2 weeks) markedly attenuated the mCPP-induced hypoactivity. Mianserin and imipramine in the absence of mCPP did not increase the animal activity. Taken together, these results indicate that the mCPP-induced hypoactivity is mediated by 5-HT2C receptor, and that selective 5-HT2C antagonists and down regulation of 5-HT2C receptor might be useful for inhibiting the mCPP-induced hypoactivity.