Autoreceptors remain functional after prolonged treatment with a serotonin reuptake inhibitor.
Serotonin (5-hydroxytryptamine, 5-HT) autoreceptors may desensitize during prolonged administration of antidepressant drugs. If autoreceptors desensitize, their inhibitory influence on extracellular 5-HT should be attenuated. To test this hypothesis, the selective serotonin reuptake inhibitor (SSRI) citalopram (10 mg kg(-1), s.c., b.i.d.) or saline was administered for 14 days to rats. After a 24-h washout period, rats were anesthetized, and implanted with dialysis probes for determination of 5-HT in the frontal cortex (FCx) and dorsal hippocampus (DH). In response to citalopram (5 mg kg(-1), s.c.) challenge, there were moderate increases in 5-HT in the FCx and DH of both the chronic citalopram and saline pretreatment groups. After subsequent administration of the 5-HT(1A/1B) autoreceptor antagonist, (-)-penbutolol, there were further increases in 5-HT in the FCx and DH of the saline pretreatment group. Moreover, contrary to the expected effect if autoreceptors were desensitized, the potentiation produced by (-)-penbutolol was greater in the FCx and DH of the chronic citalopram group as compared to rats pretreated with saline. These results suggest that autoreceptors still restrain the increase in 5-HT produced by an SSRI after prolonged administration.
Department of Pharmacology, University of Göteborg, Göteborg, Sweden.
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Hjorth
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Auerbach
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D010394:Penbutolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D017660:Autoreceptors; D015283:Citalopram; D010394:Penbutolol; D017367:Selective Serotonin Reuptake Inhibitors