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ABSTRACT: Background
Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants.Methods
The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in the rat prefrontal cortex to acute handling stress were evaluated using in vivo microdialysis.Results
Acute handling stress increased dopamine and noradrenaline levels in the prefrontal cortex. The dopamine and noradrenaline responses were suppressed by local infusion of a 5-HT1A receptor agonist, 7-(Dipropylamino)-5,6,7,8-tetrahydronaphthalen-1-ol;hydrobromide, into the prefrontal cortex. The dopamine response was abolished by long-term treatment with citalopram, and the abolished dopamine response was reversed by local infusion of a 5-HT1A receptor antagonist, (Z)-but-2-enedioic acid;N-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-pyridin-2-ylcyclohexanecarboxamide into the prefrontal cortex. On the other hand, long-term treatment with citalopram reduced the basal noradrenaline levels (approximately 40% of the controls), but not the basal dopamine levels. The noradrenaline response was maintained despite the low basal noradrenaline levels. Signaling from the 5-HT1A receptors and ?2-adrenoceptors was not involved in the decrease in the basal noradrenaline levels but partially affected the noradrenaline response.Conclusions
Chronic citalopram treatment differentially suppresses the dopamine and noradrenaline systems in the prefrontal cortex, and the dopamine stress response was preferentially controlled by upregulating 5-HT1A receptor signaling. Our findings provide insight into how antidepressants modulate the dopamine and noradrenaline systems to overcome acute stress.
SUBMITTER: Kaneko F
PROVIDER: S-EPMC5006198 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Kaneko Fumi F Kawahara Yukie Y Kishikawa Yuki Y Hanada Yuuki Y Yamada Makiko M Kakuma Tatsuyuki T Kawahara Hiroshi H Nishi Akinori A
The international journal of neuropsychopharmacology 20160812 8
<h4>Background</h4>Cortical dopamine and noradrenaline are involved in the stress response. Citalopram, a selective serotonin reuptake inhibitor, has direct and indirect effects on the serotonergic system. Furthermore, long-term treatment with citalopram affects the dopamine and noradrenaline systems, which could contribute to the therapeutic action of antidepressants.<h4>Methods</h4>The effects of long-term treatment with citalopram on the responses of the dopamine and noradrenaline systems in ...[more]