Effects of [Des-Tyr¹]-γ-endorphin and α-endorphin on substantia nigra self-stimulation

The β-lipotropin fragments, [des-Tyr¹]-γ-endorphin (DTγE, β-LPH_62-77) and α-endorphin (β-LPH_61-76) affect self-stimulating behavior associated with electrical stimulation of neurons of the ventral tegmentum area of rats in an opposite way. Subcutaneous administration of DTγE (5 and 25 μg) attenuated and that of α-endorphin (5 and 25 μg) facilitated this behavior. Similar opposite effects were observed after subcutaneous treatment with respectively the neuroleptic haloperidol (5 μg) and the psychostimulant amphetamine (100 μg). By using a biphasic testparadigm of decreasing and subsequent increasing the stimulating current intensity it was noted that the neuropeptides predominantly exerted their effect on responding at current intensities in the neighbourhood of the threshold for eliciting the behavior, whereas the neuroleptic and psychostimulant drug appeared to affect responding at currents associated with maximal performance as well. In contrast to haloperidol, the effectiveness of DTγE was of a long term nature, in that performance of the rat was still affected 24 hr after peptide treatment. The results support the hypothesis that DTγE in some aspects interacts with brain substrates in a way comparable to that of neuroleptics. The data further suggest that closely related fragments of β-lipotropin modulate on-going activity of in particular dopaminergic neuronal systems.