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Chronic citalopram administration desensitizes prefrontal cortex but not somatodendritic ?2-adrenoceptors in rat brain

Abstract: Selective serotonin reuptake inhibitors (SSRIs) regulate brain noradrenergic neurotransmission both at somatodendritic and nerve terminal areas. Previous studies have demonstrated that noradrenaline (NA) reuptake inhibitors are able to desensitize a2-adrenoceptor-mediated responses. The present study was undertaken to elucidate the effects of repeated treatment with the SSRI citalopram on the a2-adrenoceptor sensitivity in locus coeruleus (LC) and prefrontal cortex (PFC), by using in vivo microdialysis and electrophysiological techniques, and in vitro stimulation of [35S]GTPgS binding autoradiography. Repeated, but not acute, treatment with citalopram (5 mg/kg, i.p., 14 days) increased extracellular NA concentration selectively in PFC. The a2-adrenoceptor agonist clonidine (0.3 mg/kg, i.p.), administered to saline-treated animals (1 ml/kg i.p., 14 days) induced NA decrease in LC (Emax¼44 ± 4%; p < 0.001) and in PFC (Emax ¼ 61 ± 5%, p < 0.001). In citalopram chronically-treated rats, clonidine administration exerted a lower decrease of NA (Emax ¼ 25 ± 7%; p < 0.001) in PFC whereas the effect in LC was not different to controls (Emax ¼ 36 ± 4%). Clonidine administration (0.625e20 mg/kg, i.v.) evoked a dosedependent decrease of the firing activity of LC noradrenergic neurons in both citalopram- (ED50 ¼ 3.2 ± 0.4 mg/kg) and saline-treated groups (ED50 ¼ 2.6 ± 0.5 mg/kg). No significant differences between groups were found in ED50 values. The a2-adrenoceptor agonist UK14304 stimulated specific [35S]GTPgS binding in brain sections containing LC (144 ± 14%) and PFC (194 ± 32%) of saline-treated animals. In citalopram-treated animals, this increase did not differ from controls in LC (146 ± 22%) but was lower in PFC (141 ± 8%; p < 0.05). Taken together, long-term citalopram treatment induces a desensitization of a2-adrenoceptors acting as axon terminal autoreceptors in PFC without changes in somatodendritic a2-adrenoceptor sensitivity.

 Fuente: Neuropharmacology. 2017 Mar 1;114:114-122

 Publisher: Elsevier

 Year of publication: 2017

 No. of pages: 9

 Publication type: Article

 DOI: 10.1016/j.neuropharm.2016.11.025

 ISSN: 0028-3908,1873-7064

 Spanish project: SAF01/0553