Differential effects of amphetamine isomers on SN self-stimulation: evidence for DA neuron subtypes

The present experiment investigated the effects of varying doses of D- and L-amphetamine on intracranial self-stimulation (ICSS) in the medial or lateral substantia nigra (SN). It was found that the effects of D- and L-amphetamine on ICSS in the SN differ in these two sites. In the medial SN, there were no significant differences between the effects of D- and L-amphetamine on ICSS at any of the doses tested. Both isomers moderately facilitated ICSS with the peak effect at 0.8 to 2.0 mg/kg. By contrast, in the lateral SN, D-amphetamine produced a strong dose-dependent facilitation of ICSS which peaked at 2 mg/kg while L-amphetamine was ineffective below 7 mg/kg. Above 7 mg/kg L-amphetamine increased ICSS rates. The present experiments suggest that the medial and lateral SN are functionally different with respect to ICSS. The possibility that the present medial-lateral SN differences are mediated by two different types of dopamine cells is discussed. In addition, the effects of D- and L-amphetamine on ICSS in the lateral hypothalamus are discussed in light of the present findings.