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Authors & Affiliations
Zuzanna Sulich, Jakub Bilnicki, Aleksandra Kaczmarska, Joanna Bernacka, Michał Kiełbiński, Wojciech Solecki
Abstract
Stress induces catecholaminergic system adaptations implicated in the etiology of stress-related disorders. Adrenergic receptors (ARs) in the ventral tegmental area (VTA) regulate phasic dopamine (DA) release in the mesolimbic system, associated with stress-related behavioral responses. Recently we demonstrated that intra-VTA ALPHA2-ARs (but not ALPHA1-ARs) modulation of such DA release is altered by acute stress (electric footshock). However, effects of different kind of stressors (e.g. psychosocial vs physical) on intra-VTA ALPHA2-AR signaling remains to be demonstrated.We studied the impact of different stressors on the capacity of VTA ALPHA2-ARs to modulate phasic DA release in the nucleus accumbens (NAc). We used electrical stimulation of the VTA in anesthetized male rats to evoke phasic DA release in the NAc measured by fast-scan cyclic voltammetry (FSCV) following intra-VTA micro-infusion of the ALPHA2-AR antagonist RX-821002. 24 h prior to FSCV recordings all rats were subjected to physical or psychosocial stress consisting of forced swim stress (FSS) or social isolation (SI; 21 days), respectively. We used stress-naive, group-housed rats as controls. Intra-VTA micro-infusion of ALPHA2-AR antagonist RX-821002 decreased phasic DA release in the NAc in stress-naive rats. Both FSS and SI stress decreased the effects of ALPHA2-AR blockade in the VTA on phasic DA release. We demonstrated that both psychosocial and physical stressors decrease functionality of the ALPHA2-AR in the VTA. Thus, our findings indicate that stress induces similar neuroplasticity in the VTA, which modify the ability of noradrenaline to impact DA release, irrespective of stressors nature. Funding: National Science Centre grant no: UMO-2020/39/B/NZ7/03537, UMO-2018/29/B/NZ7/02672