科研之友
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摘要
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 alpha 1-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 alpha 1-adrenoceptor (3.0 mu M prazosin infusion) significantly decreased this citalopram-induced increase in serotonin, while cirazoline (alpha 1-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 mu M and 1.0 mu M 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 alpha 1-adrenoceptors may already be maximally activated under these conditions. These data provide strong evidence that after acute citalopram administration, the alpha 1-adrenoceptor exerts a modulatory role on serotonin levels.
- 出版日期2010-6
