1. Stress-induced activation of ventral tegmental mu-opioid receptors reduces accumbens dopamine tone by enhancing dopamine transmission in the medial pre-frontal cortex.
- Author
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Latagliata EC, Valzania A, Pascucci T, Campus P, Cabib S, and Puglisi-Allegra S
- Subjects
- Animals, Dopamine Agonists pharmacology, Dopamine Antagonists pharmacology, Male, Microdialysis, Naltrexone pharmacology, Narcotic Antagonists pharmacology, Neural Pathways drug effects, Neural Pathways metabolism, Nucleus Accumbens drug effects, Prefrontal Cortex drug effects, Rats, Rats, Sprague-Dawley, Receptors, Dopamine D2 metabolism, Synaptic Transmission drug effects, Ventral Tegmental Area drug effects, Dopamine metabolism, Nucleus Accumbens metabolism, Prefrontal Cortex metabolism, Receptors, Opioid, mu metabolism, Stress, Physiological physiology, Stress, Psychological metabolism, Synaptic Transmission physiology, Ventral Tegmental Area metabolism
- Abstract
Rationale: Endogenous opioids could play a major role in the mesocorticolimbic dopamine (DA) responses to stress challenge. However, there is still no direct evidence of an influence of endogenous opioids on any of these responses., Objective: We assessed whether and how endogenous opioids modulate fluctuations of mesocortical and mesoaccumbens DA tone in rats during a first experience with restraint stress., Method: We first evaluated the effects of systemic naltrexone (NTRX) on DA outflow in the medial prefrontal cortex (mpFC) and in the nucleus accumbens (NAc) through dual-probe microdialysis. Second, we assessed the effect of perfusion, through reverse microdialysis, of direct DA receptor agonists in mpFC on NAc DA outflow in NTRX-pretreated stressed rats. Finally, we tested the effects of ventral tegmental area (VTA) perfusion of NTRX, the selective mu1 antagonist naloxonazine and the selective delta antagonist naltrindole on mpFC and NAc DA outflow in stressed rats, with multiple probe experiments., Results: Systemic NTRX, at behaviorally effective doses, selectively prevented the increase of mpFC DA levels and the reduction of NAc DA levels observable during prolonged restraint. Local co-perfusion of D1 and D2 agonists in mpFC recovered inhibition of NAc DA in NTRX-pretreated restrained rats. Finally, intra-VTA perfusion of either NTRX or the mu1 antagonist, but not the delta antagonist, mimicked the effects of systemic NTRX., Conclusion: During prolonged experience with a novel unavoidable/uncontrollable stressor, endogenous opioids, through stimulation of mu1 receptors in the VTA, elevate mesocortical DA tone thus reducing DA tone in the NAc DA.
- Published
- 2014
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