title: 5-HT1A receptor antagonists increase the activity of serotonergic cells in the dorsal raphe nucleus in rats treated acutely or chronically with citalopram.
abstract: In this study we have examined the acute effects of systemic administration of the selective serotonin reuptake inhibitor (SSRI), citalopram, in combination with either of the two selective 5-HT1A receptor antagonists, [(S)-5-fluoro-8-hydroxy-2-(dipropylamino)-tetralin [(S)-UH-301] or (+)-N-tertbutyl 3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenyl-propionamide dihydrochloride [(+)-WAY100135], on the activity of single 5-HT neurons in the dorsal raphe nucleus (DRN) of anesthetized rats using extracellular recording techniques. Acute administration of citalopram (0.3 mg/kg i.v.) significantly decreased the firing rate of DRN-5-HT cells most likely as a result of indirect stimulation of inhibitory somatodendritic 5-HT1A autoreceptors located on 5-HT cells in the DRN. This effect of citalopram was completely reversed by (S)-UH-301 (0.5 mg/kg i.v.) and partly by (+)-WAY100135 (0.5 mg/kg i.v.). Furthermore, the inhibitory effect of citalopram on the activity of 5-HT neurons was significantly attenuated by pretreatment with (S)-UH-301 (0.25 mg/kg i.v.) or (+)-WAY100135 (0.25 mg/kg i.v.). We have also studied the effects of (S)-UH-301 (0.03-0.50 mg/kg i.v.) on the firing rate of single DRN-5-HT cells in rats chronically treated with citalopram (20 mg/kg/day i.p. x 14 days). Administration of (S)-UH-301 significantly and dose-dependently increased the activity of 5-HT cells in citalopram-treated rats, but did not affect these neurons in saline-treated (1 ml/kg/day i.p. x 14 days), control rats. Our results thus suggest that 5-HT1A receptor antagonists can augment both the acute and chronic effects of citalopram on central serotonergic neurotransmission.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015283:Citalopram / Q000494:pharmacology; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015283:Citalopram; D010879:Piperazines; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C064282:UH 301; C081293:WAY 100135