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1. Electrophysiological measurements of 5-HT neuronal activity report that repeated administration of 5-HT1A receptor agonists leads to desensitization of the 5-HT1A autoreceptor but this has not yet been detected in measurements of brain 5-HT synthesis or metabolism. Here we have determined the effect of repeated administration of 5-HT1A receptor agonists on brain 5-HT release using microdialysis. 2. Acute administration of the 5-HT1A receptor agonists buspirone (0.1-5 mg/kg s.c.) and ipsapirone (0.03-3 mg/kg s.c.) caused a dose-dependent decrease in 5-HT output in ventral hippocampus of the chloral hydrate anaesthetized rat. 3. The 5-HT response to buspirone (0.1 and 0.5 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was significantly inhibited by pre-treatment with the 5-HT1/beta-adrenoceptor antagonist pindolol (8-16 mg/kg s.c.). The 5-HT response to buspirone (0.1 mg/kg s.c.) and ipsapirone (0.3 mg/kg s.c.) was not blocked by pretreatment with a combination of the beta 1 and beta 2-adrenoceptor antagonists metoprolol and ICI 118,551 (4 mg/kg s.c.). 4. The effect of an acute challenge of buspirone (0.5 mg/kg s.c.) on 5-HT output in ventral hippocampus was not attenuated in rats treated twice daily for 14 days with 0.5 or 5 mg/kg s.c. buspirone compared to saline-injected controls. Similarly, the decrease in 5-HT induced by an acute challenge of ipsapirone (0.5 mg/kg s.c.) was not attenuated in rats treated twice daily for 14 days with 5 mg/kg s.c. ipsapirone.(ABSTRACT TRUNCATED AT 250 WORDS)

Type

Journal article

Journal

Naunyn Schmiedebergs Arch Pharmacol

Publication Date

10/1993

Volume

348

Pages

339 - 346

Keywords

8-Hydroxy-2-(di-n-propylamino)tetralin, Adrenergic beta-Antagonists, Animals, Brain Chemistry, Buspirone, Dose-Response Relationship, Drug, Electrodes, Implanted, Electrophysiology, Hippocampus, Male, Microdialysis, Pindolol, Pyrimidines, Rats, Rats, Sprague-Dawley, Serotonin, Serotonin Receptor Agonists