Permanent alteration of peptide feedback on dopamine neurons after injection of alpha-melanotropin antiserum at a critical period of postnatal development.

Tonic inhibition of alpha-MSH secretion by the tubero-hypophyseal dopamine (DA) neurons of the rat starts at the end of the first postnatal week, after a peak in plasma MSH at days 5 and 6. In order to obtain information on the maturation of central control, we studied the development of alpha-MSH feedback on DA neurons and the possible role of circulating peptide. The characteristic response of these DA neurons to i.p. alpha-MSH, i.e., an acute rise in cellular fluorescence intensity as determined by microfluorimetry, was not yet detected at day 4 but present at day 8. When rats were injected i.v. with antiserum to alpha-MSH on days 5 and 6 and tested as adults, their DA neurons failed to react to i.p. alpha-MSH (2-100 micrograms/kg), but they were still responsive to prolactin (600 micrograms/kg). The DA system was already unresponsive to alpha-MSH at postnatal day 8. Antiserum injection on days 11 and 12, when plasma MSH is low, did not affect the reaction of DA neurons to alpha-MSH on day 14. These developmental processes were analogous in both sexes. Injections of control serum were ineffective. Our observations indicate that the feedback reaction of DA neurons to alpha-MSH develops in conjunction with the onset of inhibitory control of MSH release. The presence of alpha-MSH during a critical period appears to be necessary for the development of the responsiveness of DA neurons to the peptide hormone.