Involvement of the entopeduncular nucleus and the habenula in methamphetamine-induced inhibition of dopamine neurons in the substantia nigra of rats.

The lateral habenula receives massive afferents from dopamine-rich forebrain areas through the stria medullaris and sends efferents to mesencephalic dopaminergic systems through the fasciculus retroflexus. In the present study, effects of electrolytic lesions of the habenula, transections of the stria medullaris, and kainic acid-induced lesions of the entopeduncular nucleus on methamphetamine-induced inhibition of substantia nigra dopamine neurons were investigated in rats. Following these lesions or transections the methamphetamine-induced inhibition on the dopamine neuronal activity was significantly attenuated compared to those in control animals with sham lesions or sham transections. Intravenous administration of methamphetamine at a dosage of 6.4 mg/kg produced only a 62.7 to 71.2% inhibition in lesioned or transected animals, whereas in control animals the activity of dopamine neurons was almost completely inhibited with this dose. The amounts of methamphetamine required to induce 50% inhibition of dopamine neurons in lesioned or transected animals was 3.3 to 4.7 times greater than those in control animals. There was no significant difference in cumulative dose-response curves between habenular-lesioned, stria medullaris-transected and entopeduncular-lesioned animals. These results, along with other findings, indicate possibly that the pathways running through the entopeduncular nucleus, the stria medullaris, the habenula, probably the lateral habenula, and the fasciculus retroflexus are involved in a feedback loop from the striatum to the substantia nigra and regulate the activity of dopamine neurons.