d-Amphetamine이 Rat의 전뇌 5-hydroxytryptamine(5-HT), 5-hydroxyindole 3-acetic acid(5-HIAA) 함량 및 Monoamine Oxidase(MAO)활성도에 미치는 영향

Abstract

Amphetamine causes a variety of CNS stimulating effects and various behavioral changes in men and animals, which were first described by Piness (1930) and Alles et al. (1933). It is well known that amphetamine induces psychosis closely mimicking paran< lid schizophrenia, and has been used as a research tool for the etiologic role of Schizophrenia. Many investigators have generally believed that .amphetarnine was a prototype activator of catecholamine mechanisms in the CNS, but more recent findings strongly suggest that 5-hydroxytryptamine(5HT) is involved in, at least, some of the effects of d. amphetarnine. Also, d-arnphetamine has been known to be a reversible inhibitor of monoamine oxidase (MAO) 'with a preference for MAO type A in vitro. This present study was set up to determine if, and 'to what extent, the turnover of 5-HT is influenced >by d-amphetamine administration. 5-HT and its major metabolite, 5-hydroxyindole.:: J-acetic acid (5-HIAA) were determined fluorometri- cally at various times after the intraperitioneal inje. ction of d-amphetamine (2mg/kg) by the combined method of Curzon and Green (1970), and Shellenberger et al. ('71). Monoamine oxidase activity of whole brain towards the substrate kynuriamine was .measured by the modified method of Kraml('65). Following results were obtained: 1. 5-HT level showed a maximal increase (126. 6% of control) at 15 min post-injection and increase lasted for 30 min, and thereafter 5-HT decreased till 24 hr post- injection, and returned to nearly control level at 48 hr after injection. 2. 5-HIAA level began to decrease at 30 min postinjection, reaching lowest levels at approximately the 1 hr-4 hr post-iniection (78% of control), and returned to control level at 24 hr after injection, and thereafter the level increased to HI. 7% of control at 48 hr post-injection. 3. MAO activity showed the lowest level at 15 min post-iniection (86. 9% of control), and thereafter slightly low activity persisted (90. 3%~97. 1% of control), till 2 hr post-injection, MAO activity began to increase at 4 hr. post-injection, reaching the highest level at 24 hr post-injection (142.7% of control). 4. 5-HIAA/5-HT ratio began to decrease at 15 min post-injection, and decrease lasted for 2 hrs. Thereafter, the ratio showed to increase, reaching the highest value at 24 hr after injection (141.1% of control). We strongly suggest that 5-hydroxytryptamine turnover is influenced by d-amphetamine administration through the effect on the activity of monoamine oxidase.