Stress-induced activation of ventral tegmental mu-opioid receptors reduces accumbens dopamine tone by enhancing dopamine transmission in the medial pre-frontal cortex

Emanuele C laudio Latagliata, Alessandro Valzania, Tiziana Pascucci, Paolo Campus, Simona Cabib, Stefano Puglisi-Allegra

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)4099-4108
Number of pages10
JournalPsychopharmacology
Volume231
Issue number21
DOIs
Publication statusPublished - Oct 1 2014

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mu Opioid Receptor
Frontal Lobe
Dopamine
Naltrexone
Nucleus Accumbens
Prefrontal Cortex
Opioid Analgesics
Ventral Tegmental Area
Perfusion
naltrindole
Microdialysis
Dopamine Agonists

ASJC Scopus subject areas

  • Medicine(all)

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Stress-induced activation of ventral tegmental mu-opioid receptors reduces accumbens dopamine tone by enhancing dopamine transmission in the medial pre-frontal cortex. / Latagliata, Emanuele C laudio; Valzania, Alessandro; Pascucci, Tiziana; Campus, Paolo; Cabib, Simona; Puglisi-Allegra, Stefano.

In: Psychopharmacology, Vol. 231, No. 21, 01.10.2014, p. 4099-4108.

Research output: Contribution to journalArticle

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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.",
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AU - Cabib, Simona

AU - Puglisi-Allegra, Stefano

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N2 - 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.

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