The effects of simultaneous or separate infusions of some pro-opiomelanocortin-derived peptides (beta-endorphin, melanocyte stimulating hormone, and corticotrophin-like intermediate polypeptide) and their acetylated derivatives upon sexual and ingestive behaviour of male rats.
Intraneuronal post-translational cleavage of pro-opiomelanocortin yields a variety of peptides including beta-endorphin, melanocyte stimulating hormone and corticotrophin-like intermediate polypeptide, some of which are subsequently N-acetylated. Such peptides may be co-released from neuronal terminals, and so these experiments explored the effects of co-administration of some of them on sexual behaviour in the male rat, which is known to be sensitive to hypothalamic infusions of beta-endorphin. Peptides were infused into the pre-optic-anterior hypothalamic area bilaterally in doses up to 320 pmol, and males allowed access to a sexually receptive female and/or a sweet solution (0.1% Acesulfame-K) for 15 min, so that both sexual and ingestive behaviour could be studied. beta-Endorphin(1-31) by itself inhibited sexual interaction, confirming our previous data. Acesulfame-K ingestion was inhibited in control-infused rats in the presence of a female, but this inhibition was released when sexual behaviour was itself diminished by beta-endorphin(1-31). Both the acetylated and non-acetylated forms of melanocyte stimulating hormone (alpha-melanocyte stimulating hormone and des-acetyl melanocyte stimulating hormone) stimulate sexual behaviour; latencies both to ejaculation and to resumption of copulatory behaviour after an ejaculation (post-ejaculatory interval) were reduced. However, infusion of either corticotrophin-like intermediate peptide or N-acetylated beta-endorphin (1-31) had no effect on either sexual or ingestive behaviour. Infusion of either acetylated melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone mixed with beta-endorphin(1-31) prevented the inhibitory effect of the latter on sexual behaviour. Dose-response studies showed that the behavioural effect of such mixtures depended upon the molar ratios of the two peptides, rather than their absolute concentrations. The higher the ratio in favour of alpha-melanocyte stimulating hormone or des-acetyl melanocyte stimulating hormone, the greater the display of sexual behaviour. Infusing either corticotrophin-like intermediate polypeptides or N-acetyl beta-endorphin(1-31) with beta-endorphin(1-31) did not prevent the inhibition of sexual activity expected with beta-endorphin(1-31) alone. These results are discussed in terms of the functional consequences of co-release of proopiomelanocortin peptides from hypothalamic nerve terminals.
Hughes
A M
AM
University of Cambridge, Department of Anatomy, U.K.
Everitt
B J
BJ
Herbert
J
J
D000107:Acetylation; D000324:Adrenocorticotropic Hormone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D053497:Corticotropin-Like Intermediate Lobe Peptide; D004723:Endorphins / Q000378:metabolism / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects*; D007032:Hypothalamus, Anterior / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009074:Melanocyte-Stimulating Hormones / Q000378:metabolism / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D000521:alpha-MSH / Q000494:pharmacology; D001615:beta-Endorphin / Q000031:analogs & derivatives / Q000494:pharmacology
D004723:Endorphins; D010446:Peptide Fragments; D053497:Corticotropin-Like Intermediate Lobe Peptide; D000521:alpha-MSH; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; C035101:N-acetyl-beta-endorphin; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones