Lyle H. Miller

Psycho-physiologic correlates of MSH activity in man

Abstract The role of MSH in man is unknown. Administration of 10 mg synthetic alpha melanocyte-stimulating hormone (MSH) to 5 human subjects resulted in a significant increase in the averaged somatosensory cortical evoked response (AER). This change in the amplitude of the somatosensory evoked response was so marked that it could be seen on single trials of the EEG. The AER further increased during attention. Performance on the Benton Visual Retention Test also improved significantly after infusion of MSH. These findings demonstrate extra-pigmentary effects of MSH in man and suggest an effect upon the attentive process.

A neuroheptapeptide influence on cognitive functioning in the elderly.

The heptapeptide core common to melanocyte-stimulating hormone (MSH) and adrenocorticotropin (ACTH) was administered as a single subcutaneous dose of 30 mg to 13 elderly human subjects (9 men, 4 women) in a double-blind, cross-over design. Significant improvement was found in the Benton Visual Retention Test after MSH/ACTH 4--10 as compared with administration of saline. This appeared to be greater in men than women. No side effects or laboratory abnormalities were observed. The behavioral results are consistent with our earlier findings in men and rats of improved visual attention after administration of MSH and extend them to the elderly population.

Effect of high doses of naloxone on shuttle avoidance acquisition in rats

Administration of high doses of naloxone intraperitoneally (2.5-10.0 mg/kg) resulted in a dose-related impairment of avoidance response acquisition in a shuttle avoidance paradigm in rats. Naloxone in this dose range produced a significant decrease in the number of intertrial responses but did not result in a significant dose-response. Escape latencies were not affected by naloxone administration at any dose tested. The effect of naloxone on activity and nociception are implicated as possible causes of the observed behavior. The results are discussed as behavioral evidence supporting theories postulating multiple opiate receptors.

Inverse relationship between onset and duration of EEG effects of six peripherally administered peptides

Electrical activity in the rat brain after the peripheral injection of equimolar (0.1 mM) doses of Metenkephalin, Leu-enkephalin, beta-endorphin, gamma-endorphin, DSIP, and alpha-MSH was assessed by power spectral analysis. The mean onset of EEG activity for each peptide varied between 13.7 and 20.7 minutes and lasted between 27.8 and 40.8 minutes. The significant (p less than 0.001) interaction between duration and latency revealed that the longer the latency, the shorter the duration. Similar findings were observed after injection of the same peptides at a fixed dose of 80 microgram/kg body weight. Thus, the results demonstrate that peripherally injected peptides can exert EEG effects that last longer the sooner they start.

The effect of MSH/ACTH 4–10 on delayed response performance and post-test locomotor activity in rats

Delayed response performance was measured in male, Long-Evans rats 1 hr after IP administration of various doses of MSH/ACTH 4-10 or control in a Hunter delayed reaction apparatus. Additional treatments consisting of naloxone 500 micrograms/kg (IP) and naloxone 500 micrograms/kg in conjunction with MSH/ACTH 4-10 95 micrograms/kg were also administered. Directly after delayed response performance was assessed, gross locomotor activity was determined. MSH/ACTH 4-10, at a dose of 95 micrograms/kg, significantly enhanced retention of a visual stimulus, while MSH/ACTH 4-10, at doses of 195 and 285 micrograms/kg, significantly impaired delayed response performance. Naloxone treatment resulted in significantly impaired delayed response performance when compared to control. However, naloxone plus MSH/ACTH 4-10 treatment failed to produce a significant difference from control in the delayed response performance paradigm. In post-test locomotor activity determination, an apparent dose-response existed for MSH/ACTH 4-10 with the two highest doses (190 and 285 micrograms/kg) resulting in significantly increased locomotor activity. The observed delayed response performance data support theories implicating MSH/ACTH peptides in attentional processes involving visual stimuli. The fact that large doses of MSH/ACTH 4-10 disrupt delayed response performance while increasing post-test activity suggest that an optimum level of effect caused by the MSH/ACTH peptide exists in this paradigm.

Abba Kastin: The melanocyte stimulating hormone story and the future of the proteophathies

From a personal viewpoint, Abba was always a congenial colleague and a good friend. I recall the hours of unraveling complex, confusing, and many times contradictory data sets with him and the excitement we both felt as what had been puzzling began to make sense. Most of all, I feel privileged to have Abba as a long and valued friend.