The study by Johnson and North investigates the mechanism by which opioids excite dopamine-containing neurons in the ventral tegmental area (VTA), a critical region for the reinforcing effects of drugs of abuse. Intracellular recordings from rat brain slices revealed that opioids do not directly affect principal (dopamine-containing) neurons but hyperpolarize secondary (GABA-containing) interneurons. This hyperpolarization is mediated by μ-opioid receptors and reduces the frequency of spontaneous GABA-mediated synaptic potentials in the principal cells. The authors conclude that opioids excite dopamine-containing neurons through disinhibition, reducing the inhibitory input from local interneurons, which contributes to the positive reinforcement seen with μ-receptor agonists like morphine and heroin. The findings support the dopaminergic hypothesis of reward, suggesting that opioids enhance dopamine release in limbic regions such as the nucleus accumbens.The study by Johnson and North investigates the mechanism by which opioids excite dopamine-containing neurons in the ventral tegmental area (VTA), a critical region for the reinforcing effects of drugs of abuse. Intracellular recordings from rat brain slices revealed that opioids do not directly affect principal (dopamine-containing) neurons but hyperpolarize secondary (GABA-containing) interneurons. This hyperpolarization is mediated by μ-opioid receptors and reduces the frequency of spontaneous GABA-mediated synaptic potentials in the principal cells. The authors conclude that opioids excite dopamine-containing neurons through disinhibition, reducing the inhibitory input from local interneurons, which contributes to the positive reinforcement seen with μ-receptor agonists like morphine and heroin. The findings support the dopaminergic hypothesis of reward, suggesting that opioids enhance dopamine release in limbic regions such as the nucleus accumbens.