Effects of methiothepin on changes in brain serotonin release induced by repeated administration of high doses of anorectic serotoninergic drugs

摘要: We previously observed, using in vivo microdialysis, that the potassium-evoked release of frontocortical serotonin (5-HT) is suppressed after rats receive high doses (30 mg/kg, i.p., daily for 3 days) fluoxetine, a selective blocker 5-HT reuptake. now describe similar impairments repeated administration two other uptake blockers, zimelidine and sertraline (both at 20 i.p. as well dexfenfluramine (7.5 days), drug which both releases blocks its Doses these indirect agonists were about 4-6 times drug's ED50 producing anorexia, serotonin-related behavior. In addition, methiothepin (20 microM), non-selective receptor antagonist, locally perfused through dialysis probe 24 h last injection, enhanced K(+)-evoked serotoninergic nerve terminals markedly control slightly treated with or fluoxetine. On hand, pretreatment (10 i.p.) one hour before each fluoxetine given days, totally prevented decrease basal 5-HT. Finally, when was injected systemically day first injections dexfenfluramine, it partially attenuated long-term depletion brain 5-HIAA levels induced by dexfenfluramine. These data suggest drugs bring prolonged blockade reuptake - such can, causing increases intrasynaptic measured produce receptor-mediated changes processes controlling dynamics.