Alpha1-adrenoceptors modulate citalopram-induced serotonin release.
Previous studies suggest that noradrenaline may regulate serotonergic (5-HT) neurotransmission at the serotonin cell body and noradrenaline nerve terminal. Using microdialysis coupled to HPLC, we investigated the effects of alpha1-adrenoceptor manipulation on extracellular serotonin levels - in the ventral hippocampus, prefrontal cortex, and raphe nuclei - in the presence or absence of the serotonin reuptake inhibitor (SSRI), citalopram. Extracellular 5-HT levels from prefrontal cortex, ventral hippocampus and raphe nuclei were markedly increased following citalopram administration (3.0 mg/kg s.c.). In the prefrontal cortex and ventral hippocampus, local blockade of the alpha1-adrenoceptor (3.0 microM prazosin infusion) significantly decreased this citalopram-induced increase in serotonin, while cirazoline (alpha1-adrenoceptor agonist) and reboxetine (noradrenaline reuptake inhibitor) further increased extracellular serotonin levels when administered systemically (0.02 mg/kg i.p. and 5.0 mg/kg s.c. respectively) or locally infused (10.0 microM and 1.0 microM respectively). Moreover, prazosin pre-infusion into terminal areas prevented the increase in citalopram-induced increase in serotonin levels with systemic cirazoline or reboxetine administration. Prazosin also decreased the citalopram-induced increase in serotonin levels in the raphe nuclei; however no enhancement of the SSRI response was observed with systemic or local administration of cirazoline or reboxetine, suggesting that alpha1-adrenoceptors may already be maximally activated under these conditions. These data provide strong evidence that after acute citalopram administration, the alpha1-adrenoceptor exerts a modulatory role on serotonin levels.
Rea
Kieran
K
Department of Pharmacology, National University of Ireland, Galway, Ireland.
Folgering
Joost
J
Westerink
Ben H C
BH
Cremers
Thomas I F H
TI
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D018759:Adrenergic Uptake Inhibitors; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D015283:Citalopram; D007093:Imidazoles; D009025:Morpholines; D011224:Prazosin; D000077593:Reboxetine; D018340:Receptors, Adrenergic, alpha-1; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C014282:cirazoline