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Effects of delta opioid receptors activation on a response inhibition task in rats

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Abstract

Rationale

Response inhibition, a primary symptom of many psychiatric disorders, is mediated through a complex neuropharmacological network that involves dopamine, serotonin, glutamate, noradrenaline, and cannabinoid mechanisms. Recently, we identified an opioidergic contribution to response inhibition by showing that deletion of mu or delta opioid receptors in mice alters motor impulsivity.

Objectives

We investigated this phenomenon further by testing whether pharmacological activation of opioid receptors disrupts the ability to inhibit a motor response.

Methods

Long–Evans rats were trained to withhold a lever-pressing response for sucrose until a discriminative stimulus (lever light) was presented. The delay to the discriminative stimulus (1 to 60 s) was varied, so animals could not predict, on any given trial, the length of the pre-response phase. Motor impulsivity was assessed as the inability to inhibit lever pressing prior to the discriminative stimulus. Rats were tested following an injection of the mu opioid receptor agonist morphine (0, 0.5, 1, 2, 4, 6, 8, or 10 mg/kg) or the delta receptor agonist SNC80 (0, 2.5, 5, or 10 mg/kg).

Results

SNC80 (10 mg/kg) increased premature responses and locomotor activity, but had no effect on the speed of responding or non-reinforced presses. The SNC80-induced decrease in accuracy was blocked by the delta opioid receptor antagonist naltrindole. Morphine had no effect on accuracy but increased locomotor activity (2 mg/kg).

Conclusions

These findings point to a role for delta, but not mu, opioid receptors in disinhibition as measured in the response inhibition task. The results appear to contradict those of previous opioid receptor deletion studies; possible sources of these discrepant results are discussed.

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Authors and Affiliations

  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département Neurobiologie et Génétique, INSERM, CNRS, Université de Strasbourg, Illkirch, France

    Katia Befort & Brigitte L. Kieffer

  2. Department of Psychology, Queen’s University, Kingston, ON, K7L 3N6, Canada

    Megan K. Mahoney, Carmen Chow & Mary C. Olmstead

  3. Centre for Neuroscience Studies, Queen’s University, Kingston, ON, Canada

    Scott J. Hayton & Mary C. Olmstead

Authors
  1. Katia Befort
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  2. Megan K. Mahoney
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  3. Carmen Chow
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  4. Scott J. Hayton
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  5. Brigitte L. Kieffer
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  6. Mary C. Olmstead
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Corresponding author

Correspondence to Mary C. Olmstead.

Additional information

This research was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) and le Centre National de la Recherche Scientifique (CNRS). We thank Roland Dupras, Lisa Miller, and Sarah Holden for technical assistance.

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Befort, K., Mahoney, M.K., Chow, C. et al. Effects of delta opioid receptors activation on a response inhibition task in rats. Psychopharmacology 214, 967–976 (2011). https://doi.org/10.1007/s00213-010-2108-0

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  • DOI: https://doi.org/10.1007/s00213-010-2108-0

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