Alpha-MSH and MIF-I effects on catecholamine levels and synthesis in various rat brain areas.

Attempts were made to find a biochemical correlate with previously observed behavioral alterations after administration of alpha-melanocyte-stimulating hormone (MSH) and MSH release-inhibiting factor (MIF-I). Brains of intact and hypophysectomized (hypox) rats were analyzed for endogenous catecholamine levels and the disappearance rate of endogenous norepinephrine (NE) after treatment with the tyrosine hydroxylase inhibitor alpha-methyl-para-tyrosine (AMPT). The studies undertaken show the following: (1) After the injection of MSH (100 mug/kg IP daily x 3) and AMPT, samples in different groups of intact and hypox rats were taken at 0, 1, 2, 4 and 6 hrs in 7 different brain areas. In the mid-brain area for the intact group of rats, the rate of disappearance of NE was faster and for the hypox rats it was slower than the rate for control rats not treated with the peptides. NE levels in the same area at time 0 were 11 percent lower than controls in hypox rats and unchanged in unoperated animals. (2) After the injection of MIF-I (20 mg/kg IP daily x 3) in similar experiments as with MSH, a reduced rate (p less than 0.05) of NE disappearance for the first 4 hr and an increased rate (p less than 0.05) of NE disappearance for the last 2 hr of the experiments occurred for both the intact and hypox rats in the mid-brain area where endogenous NE levels were lowered by 11 and 12 percent at 0 min. In no other brain areas were alterations in NE breakdown found in both the intact and hypox rat groups. Behavioral changes have been found previously under similar experimental conditions in both intact and hypox rats. (3) Rates of dopamine disappearance in experiments similar to those described for NE disappearance indicated that in the striatal brain area no change was found in the intact rats after either MSH or MIF-I, whereas a decrease in DA disappearance was found for hypox rats during the six hour experimental period only after MSH. The results indicate that a correlation between behavioral changes, rates of disappearance and endogenous levels of NE in the mid-brain area may occur after MIF-I at the times examined but that a similar correlation for MSH did not appear likely.