Involvement of δ- and μ-opioid receptors in the potentiation of brain-stimulation reward

Abstract

A rate-free method of determining brain-stimulation reward thresholds was used to identify the rewarding effects of the δ-opioid receptor and μ-opioid receptor agonist peptides, [d-Pen², d-Pen⁵]enkephalin (DPDPE) and [d-Ala²-MePhe⁴-Gly(ol)⁵]enkephalin (DAMGO). The nucleus accumbens-delivered opioid receptor agonists produced marked lowering of the threshold for ventral tegmental area brain-stimulation reward. No change in baseline thresholds was seen after peripheral administration of the nonpeptide δ-opioid receptor antagonist, naltrindole. However, an unexpected finding was that naltrindole blocked the threshold-lowering effects of both DPDPE and DAMGO. These data demonstrate nucleus accumbens activation of δ- and μ-opioid receptors and ventral tegmental area brain-stimulation reward share common brain substrates. In addition, the interference of both δ- and μ-opioid receptor mediated reward by naltrindole may have implications for therapeutic use.