Acute stress modulates noradrenergic signaling in the ventral tegmental area-amygdalar circuit.

Michal Kielbinski, Joanna Bernacka, Katarzyna Zajda, Agnieszka Wawrzczak-Bargieła, Marzena Maćkowiak, Ryszard Przewlocki, Wojciech Solecki

Journal of neurochemistry 2023 Mar

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Noradrenergic neurotransmission is a critical mediator of stress responses. In turn, exposure to stress induces noradrenergic system adaptations, some of which are implicated in the etiology of stress-related disorders. Adrenergic receptors (ARs) in the ventral tegmental area (VTA) have been demonstrated to regulate phasic dopamine (DA) release in the forebrain, necessary for behavioral responses to conditional cues. However, the impact of stress on noradrenergic modulation of the VTA has not been previously explored. We demonstrate that ARs in the VTA regulate dopaminergic activity in the VTA-BLA (basolateral amygdala) circuit, a key system for processing stress-related stimuli; and that such control is altered by acute stress. We utilized fast-scan cyclic voltammetry to assess the effects of intra-VTA microinfusion of α1 -AR and α2 -AR antagonists (terazosin and RX-821002, respectively), on electrically evoked phasic DA release in the BLA in stress-naïve and stressed (unavoidable electric shocks - UES) anesthetized male Sprague-Dawley rats. In addition, we used western blotting to explore UES-induced alterations in AR protein level in the VTA. Intra-VTA terazosin or RX-821002 dose-dependently attenuated DA release in the BLA. Interestingly, UES decreased the effects of intra-VTA α2 -AR blockade on DA release (24 h but not 7 days after stress), while the effects of terazosin were unchanged. Despite changes in α2 -AR physiological function in the VTA, UES did not alter α2 -AR protein levels in either intracellular or membrane fractions. These findings demonstrate that NA-ergic modulation of the VTA-BLA circuit undergoes significant alterations in response to acute stress, with α2 -AR signaling indicated as a key target. © 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Citation

Michal Kielbinski, Joanna Bernacka, Katarzyna Zajda, Agnieszka Wawrzczak-Bargieła, Marzena Maćkowiak, Ryszard Przewlocki, Wojciech Solecki. Acute stress modulates noradrenergic signaling in the ventral tegmental area-amygdalar circuit. Journal of neurochemistry. 2023 Mar;164(5):598-612