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

Abstract

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.

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

“…Individual mice were gently placed in a glass cylinder (height 45 cm; diameter 25 cm) containing 20 cm water at 28 ± 2 • C. Although Porsolt Test (PT) is usually performed in two sessions, 24 h (or longer) apart, we tested animals in only one session, because our aim was to assess their coping strategies in a stressful condition [40,145]. Mice were maintained in the apparatus for 6 min.…”

Serotonin and stress coping

“…The DRN-5HT system is a very important modulator of GABAergic system in BLA and alterations of this modulatory function are associated with stress-related psychopathology [130,131]. In line with this view, an increase in mpFC 5-HT release causes an increase of GABA release in BLA and induces passive coping behavior during FST [121]. It should be noted that the BLA, through gluramatergic projections [132,133] sends efferent to the nucleus accumbens a brain area that has a major role in stress-coping behavior [6].…”

“…This is indicated by evidence that sustained stress-induced 5-HT outflow in mpFC leads to sustained immobility, while prefrontal 5-HT depletion leads to low immobility in the FST [121]. The majority of pyramidal neurons is functionally inhibited by 5-HT in a 5-HT1A-dependent manner supporting the hypothesis that 5-HT1A receptors play a major role in modulating pyramidal neuron activity [122].…”

“…In line with this hypothesis, unpublished evidence has shown that inter-individual variability in coping styles during the FST of two different strains of mice is related by a difference in mpFC 5-HT release and mpFC 5-HT1A receptor levels (Andolina et al, submitted). The DRN-5-HT system plays a critical role in the modulation of amygdala during the stress response influencing stress coping behavior modulated by this area [121,[127][128][129] also through CRF2 receptors [103][104][105]. The DRN-5HT system is a very important modulator of GABAergic system in BLA and alterations of this modulatory function are associated with stress-related psychopathology [130,131].…”

Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test

“…Learning-associated plasticity and epigenetic markers have been identified in the hippocampus of rats and mice with FST experience [8,10] and there is evidence of the involvement of amygdala [10][11][12], frontal cortex [12][13][14][15], ventral striatum [14,15] and dorsal striatum [16,17] in the acquisition and/or memory consolidation of the first experience with FST. We have recently reported that the brain area involved in consolidation of FST memory depends on genotype.…”