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

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.