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Authors & Affiliations
Jakub Bilnicki, Aleksandra Kaczmarska, Zuzanna Sulich, Wojciech Solecki
Abstract
Reinforcement learning requires phasic dopamine (DA) release in the forebrain. Canonical hypothesis explaining reinforcing effects of opioids points to a critical role of the activation of the mu opioid receptors (MOR) in the in the ventral tegmental area (VTA). These receptors are thought to be expressed on the local GABAergic interneurons, and their activation leads to GABAergic neurons inhibition, which in turn disinhibit dopaminergic cells. Such disinhibition increases dopamine (DA) release in the nucleus accumbens (NAc). However the mode of DA release (tonic vs phasic) is not well differentiated and whether phasic DA release is facilitated by MOR activation remains to be demonstrated. Here, we aimed to determine the role of the MOR in the VTA in modulating phasic DA release in the NAc.We used fast-scan cyclic voltammetry (FSCV) in anesthetized male Sprague-Dawley rats to study DA release induced by electrical stimulation of the VTA. Different stimulation parameters were used to induce tonic or phasic DA release in the NAc. To determine the role of MOR in the VTA we used local micro-infusions of selective MOR agonist (DAMGO) and antagonist (CTAP). Both DAMGO and CTAP had no effects on phasic DA release in the NAc. Additional analysis were performed demonstrating potential DAMGO and CTAP effects depending on the site of local micro-infusion.Our preliminary results indicate limited role of VTA MOR modulation of phasic DA release and suggest heterogeneity within the VTA-NAc circuitry in response to opioids.Funding: National Science Centre Research grant no: UMO-2020/39/B/NZ7/03537