Prefrontal/Amygdalar System Determines Stress Coping Behavior Through 5-HT/GABA Connection

• DOI: 10.1038/npp.2013.107
• Publication Date: 2013-05-02T15:00:43Z
• Authors: Diego Andolina; Dario Maran; Alessandro Valzania; David Conversi; Stefano Puglisi-A...
• Keywords: Male; 0301 basic medicine; Serotonin; Microinjections; Dopamine; 5,7-Dihydroxytryptamine; Allylglycine; Brain; Prefrontal Cortex; Immobility Response, Tonic; Amygdala; GABA Antagonists; Mice; Norepinephrine; 03 medical and health sciences; 0302 clinical medicine; Adaptation, Psychological; Neural Pathways; coping; corticolimbic; disconnection; GABA; serotonin; 5,7-Dihydroxytryptamine; Adaptation, Psychological; Allylglycine; Amygdala; Animals; Brain; Dopamine; GABA Antagonists; Immobility Response, Tonic; Male; Mice; Microinjections; Neural Pathways; Norepinephrine; Prefrontal Cortex; Serotonin; Stress, Psychological; gamma-Aminobutyric Acid; Pharmacology; Psychiatry and Mental Health; Animals; Stress, Psychological; gamma-Aminobutyric Acid

Coping is defined as the behavioral and physiological effort made to master stressful situations. The ability to cope with stress leads either to healthy or to pathogenic outcomes. The medial prefrontal cortex (mpFC) and amygdala are acknowledged as having a major role in stress-related behaviors, and mpFC has a critical role in the regulation of amygdala-mediated arousal in response to emotionally salient stimuli. Prefrontal cortical serotonin (5-hydroxytryptamine (5-HT)) is involved in corticolimbic circuitry, and GABA has a major role in amygdala functioning. Here, using mice, it was assessed whether amygdalar GABA regulation by prefrontal 5-HT is involved in processing stressful experiences and in determining coping outcomes. First (experiment 1), bilateral selective 5-HT depletion in mpFC of mice reduced GABA release induced by stress in basolateral amygdala (BLA) and passive coping in the Forced Swimming Test (FST) (experiment 2). Moreover, prefrontal-amygdala disconnection procedure that combined a selective unilateral 5-HT depletion of mpFC and infusion of an inhibitor of GABA synthesis into the contralateral BLA, thereby to disrupt prefrontal-amygdalar serial connectivity bilaterally, showed that disconnection selectively decreases immobility in the FST. These results point to prefrontal/amygdala connectivity mediated by 5-HT and GABA transmission as a critical neural mechanism in stress-induced behavior.