Research ArticleAddiction

µ-Opioid receptor–induced synaptic plasticity in dopamine neurons mediates the rewarding properties of anabolic androgenic steroids

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Science Signaling  01 Sep 2020:
Vol. 13, Issue 647, eaba1169
DOI: 10.1126/scisignal.aba1169

Opioid signaling mediates steroid abuse

The dopamine system in the brain mediates feelings of “reward” and is implicated in addiction to various drugs, including anabolic androgenic steroids. Bontempi and Bonci found that the neurological and behavioral effects of androgenic steroids were mediated not by androgen receptors but indirectly by opioid receptors on dopaminergic neurons. A single subcutaneous injection of the steroids nandrolone or testosterone in mice stimulated the release of β-endorphins in a dopaminergic neuron-rich brain region. β-Endorphins activated mu (μ)–opioid receptor (MOR) signaling, which induced excitatory synaptic plasticity in neurons. Blocking MOR activation prevented drug-seeking behavior in steroid-injected mice. The findings may explain the addictive nature of anabolic steroid use.

Abstract

Anabolic androgenic steroids (AAS) have medical utility but are often abused, and the effects of AAS on reward circuits in the brain have been suggested to lead to addiction. We investigated the previously reported correlations between AAS and the endogenous μ-opioid system in the rewarding properties of AAS in mice. We found that a single injection of a supraphysiological dose of natural or synthetic AAS strengthened excitatory synaptic transmission in putative ventral tegmental area (VTA) dopaminergic neurons. This effect was associated with the activation of μ-opioid receptors (MORs) and an increase in β-endorphins released into the VTA and the plasma. Irreversible blockade of MORs in the VTA counteracted two drug-seeking behaviors, locomotor activity and place preference. These data suggest that AAS indirectly stimulate a dopaminergic reward center of the brain through activation of endogenous opioid signaling and that this mechanism mediates the addictive effects of AAS.

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