Effects of delta opioid receptors activation on a response inhibition task in rats
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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.
We investigated this phenomenon further by testing whether pharmacological activation of opioid receptors disrupts the ability to inhibit a motor response.
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).
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).
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.
KeywordsOpiate Inhibition Morphine Disinhibition Drug abuse Cognition Motor impulsivity
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