Neuroscience Vol. 27, No. 2, Pp. 689-698, 1988 Printed in Great Britain 0306-4522/88 $3.00 + 0.00 Pergamon Press plc IBRO THE EFFECTS OF SIMULTANEOUS OR SEPARATE INFUSIONS OF SOME PRO-OPIOMELANOCORTIN- DERIVED PEPTIDES (/?-ENDORPHIN, MELANOCYTE STIMULATING HORMONE, AND CORTICOTROPHIN-LIKE INTERMEDIATE POLYPEPTIDE) AND THEIR ACETYLATED DERIVATIVES UPON SEXUAL AND INGESTIVE BEHAVIOUR OF MALE RATS A. M. HUGHES, B. J. EVERITT and J. HERBERT* University of Cambridge, Department of Anatomy, Downing Street, Cambridge CB2 3DY, U.K. Abstract-Intraneuronal post-translational cleavage of pro-opiomelanocortin yields a variety of peptides including B-endorphin, melanocyte stimulating hormone and corticotrophin-like intermediate poly- peptide, 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 /?-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. fi-Endorphin(l-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 /I-endorphin(l-31). Both the acetylated and non- acetylated forms of melanocyte stimulating hormone (a-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, infusions of either corticotrophin-like intermediate peptide or N-acetylated /I-endorphin(l-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 b-endorphin(l-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 a-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 /?-endorphin(l-31) with /I-endorphin(l-31) did not prevent the inhibition of sexual activity expected with B-endorphin(l-31) alone. These results are discussed in terms of the functional consequences of co-release of pro- opiomelanocortin peptides from hypothalamic nerve terminals. fl-Endorphin, infused bilaterally into the preoptic area-anterior hypothalamus (POA) of sexually active male rats, inhibits copulatory behaviour in a dose- dependent manner, an effect which can be reversed by prior treatment with opiate antagonists, given either intraperitoneally or directly into the POA.” Uni- lateral infusions, like unilateral hypothalamic lesions, are ineffective.” Infusions of /?-endorphin into the adjacent ventromedial hypothalamus (VMH) or bed nucleus of the stria terminalis (BNST) had no effect *To whom correspondence should be addressed. Abbreuiarions: ACTH, adrenocorticotrophic hormone; BNST, bed nucleus of the stria terminalis; CLIP, corticotrophin-like intermediate polypeptide; CSF, cere- brospinal fluid; MSH, melanocyte stimulating hormone; PEI, post-ejaculatory interval; POA, preoptic area- anterior hypothalamus; POMC, pro-opiomelanocortin; VMH, ventromedial hypothalamus. on sexual activity. /?-Endorphin did not affect inges- tive behaviour, in contrast to its effect on sexual behaviour. fl-Endorphin in the POA is found in terminals arising from pro-opiomelanocortin (POMC)-con- taining groups of neurons located largely within and around the hypothalamic arcuate nucleus.‘0J3 In the CNS, the 3 1,000 mol. wt POMC molecule is first cleaved to form C-terminal p-lipotrophin, which is then further processed to /?-endorphin and adreno- corticotrophic hormone (ACTH).‘* The last sub- stance is then cleaved to yield des-acetyl melanocyte stimulating hormone (des-acetyl MSH) and cortico- trophin-like intermediate lobe polypeptide (CLIP), a process which is different from that occurring in the pituitary.‘* Within neurons in the CNS, therefore, B-endorphin co-exists with other peptides derived from the POMC precursor, which include des-acetyl MSH and CLIP. 689