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Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens

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Abstract

Rationale

Kappa opioid receptors (KORs) have been implicated in depressive-like states associated with chronic administration of drugs of abuse and stress. Although KOR agonists decrease dopamine in the nucleus accumbens (NAc), KOR modulation of phasic dopamine release in the core and shell subregions of the NAc—which have distinct roles in reward processing—remains poorly understood.

Objectives

Studies were designed to examine whether the time course of effects of KOR activation on phasic dopamine release in the NAc core or shell are similar to effects on motivated behavior.

Methods

The effect of systemic administration of the KOR agonist salvinorin A (salvA)—at a dose (2.0 mg/kg) previously determined to have depressive-like effects—was measured on electrically evoked phasic dopamine release in the NAc core or shell of awake and behaving rats using fast scan cyclic voltammetry. In parallel, the effects of salvA on intracranial self-stimulation (ICSS) and sucrose-reinforced responding were assessed. For comparison, a threshold dose of salvA (0.25 mg/kg) was also tested.

Results

The active, but not threshold, dose of salvA significantly decreased phasic dopamine release without affecting dopamine reuptake in the NAc core and shell. SalvA increased ICSS thresholds and significantly lowered breakpoint on the progressive ratio schedule, indicating a decrease in motivation. The time course of the KOR-mediated decrease in dopamine in the core was qualitatively similar to the effects on motivated behavior.

Conclusions

These data suggest that the effects of KOR activation on motivation are due, in part, to inhibition of phasic dopamine signaling in the NAc core.

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Acknowledgements

This work was supported by the Morris D. Braun Foundation (EHC) and by National Institutes of Health grants DA023094 (to EHC) and DA025634 (to MFR) and NARSAD (to MFR).

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Authors and Affiliations

  1. Department of Psychology, University of Illinois at Chicago, Chicago, IL, 60607, USA

    Stephanie R. Ebner & Mitchell F. Roitman

  2. Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 218, 115 Mill Street, Belmont, MA, 02478, USA

    David N. Potter, Anna B. Rachlin & Elena H. Chartoff

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  1. Stephanie R. Ebner
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  2. Mitchell F. Roitman
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  3. David N. Potter
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Correspondence to Elena H. Chartoff.

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Ebner, S.R., Roitman, M.F., Potter, D.N. et al. Depressive-like effects of the kappa opioid receptor agonist salvinorin A are associated with decreased phasic dopamine release in the nucleus accumbens. Psychopharmacology 210, 241–252 (2010). https://doi.org/10.1007/s00213-010-1836-5

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