Morphine increases the activity of midbrain dopamine neurons in vitro

Morphine produced a dose-dependent increase in the activity of dopamine-containing neurons in the substantia nigra and ventral tegmental area recorded from mouse brain slices in vitro. The response was not changed in a low calcium/high magnesium incubation medium, indicating that the observed effects are the result of the direct action of morphine on dopamine neurons. Furthermore, a specific opiate antagonist, naloxone, versed the excitatory effects of morphine in both brain regions, while naloxone alone had no significant effect on the activity of dopaminergic neurons. Morphine was more potent on ventral tegmental area than substantia nigra dopamine neurons. β-Endorphin excited ventral tegmental area neurons but not substantia nigra cells, while [Leu⁵]enkephalin activated cells in both nuclei. These latter responses were blocked by naloxone. These data suggest that midbrain dopamine neurons contain receptors for opiates, and that ventral tegmental area neurons are more sensitive to the action of opiates than substantia nigra neurons.