The rewarding properties of MDMA are preserved in mice lacking µ‐opioid receptors

The rewarding effects of MDMA do not require µ-opioid receptors, unlike those of opioids, ethanol, nicotine, and THC. In mice lacking µ-opioid receptors, MDMA still produced a conditioned place preference and increased dopamine release in the nucleus accumbens, while decreasing dopamine metabolites DOPAC and HVA. Basal dopamine and metabolite levels were similar between knockout and wild-type mice. The findings indicate that MDMA's effects on dopamine neurons are independent of µ-opioid receptor activation.

Study at a glance

Abstract

Abstract The involvement of µ‐opioid receptors in the rewarding properties of MDMA was explored in µ‐opioid receptor knockout mice using the conditioning place preference paradigm. The associated release of dopamine in the nucleus accumbens was investigated by in vivo microdialysis. A significant rewarding effect of MDMA (10 mg/kg, i.p.) was observed in both wild‐type and µ‐opioid receptor knockout mice. MDMA (10 mg/kg, i.p.) also induced similar increases in dopamine and decreases in 3,4‐dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens dialysates of both wild‐type and µ‐opioid receptor knockout mice. No significant differences in basal levels of dopamine, 3,4‐dihydroxyphenylacetic or homovanillic acids between wild‐type and µ‐opioid receptor knockout mice were observed. In summary, the present results suggest that, in contrast to what has been reported for other drugs of abuse such as opioids, ethanol, nicotine and Δ 9 ‐tetrahydrocannabinol, µ‐opioid receptors do not play a major role in the rewarding properties of MDMA. These differences could be due to distinct mechanisms controlling dopamine release in the nucleus accumbens and suggest that the effects of MDMA on dopaminergic neurons are independent of µ‐opioid receptors.