Midbrain dopamine neurons: differential responses to amphetamine isomers

Intravenously administered d- and l-amphetamine have different potency ratios in reducing the firing rates of dopamine cells in the substantia nigra and in the ventral tegmental area. While d-amphetamine is considerably more potent than l-amphetamine in reducing ventral substantia nigra dopamine neuronal impulse flow, d- and l-amphetamine are of similar potency in reducing dorsal substantia nigra and ventral tegmental dopamine neuronal impulse flow. These results suggest that all dopamine cell groups are not pharmacologically identical and that different dopamine nuclei may respond differently to psychoactive drugs. The comparable potencies of the d- and l-isomers on dorsal substantia nigra and ventral tegmental area dopamine neurons may explain, by a dopamine mechanism, the finding that comparable doses of the isomers produce schizophrenic-like symptoms.