The new kisspeptin derivative - kissorphin (KSO) - attenuates acute hyperlocomotion and sensitization induced by ethanol and morphine in mice.

Abstract

Kissorphin (KSO) is a new peptide derived from kisspeptin-10. This peptide possesses neuropeptide FF (NPFF)-like biological activity invitro; NPFF, in many cases, inhibits opioid and ethanol effects in rodents. Therefore, the current study explored the influence of KSO on acute ethanol- and morphine-induced hyperactivity, and on the development and expression of locomotor sensitization induced by these drugs. In the present study, sensitization to locomotor effects was induced by repeated exposure to ethanol (2.4g/kg, intraperitoneally [i.p.], 1×4 days) or morphine (10mg/kg, subcutaneously [s.c.], 1×7 days). We found that KSO (1-10nmol/300μL, intravenously [i.v.]) did not have an impact on locomotor activity of naïve mice. However, it reduced both acute ethanol- (10nmol/300μL) and morphine-induced hyperactivity (3 and 10nmol/300μL). Pretreatment of animals with KSO (10nmol/300μL), before every ethanol or morphine injection during development of sensitization or before the ethanol or morphine challenge, attenuated the development, as well as the expression of locomotor sensitization to both substances. Moreover, prior administration of the NPFF receptor antagonist RF9 (10nmol/300μL, i.v.) inhibited the ability of KSO (10nmol/300μL) to reduce the expression of ethanol and morphine sensitization. KSO given alone, at all used doses, did not influence the motor coordination measured via the rotarod test. The results from this study show that KSO effectively attenuated acute and repeated effects of ethanol and morphine. Thus, KSO possesses NPFF-like anti-opioid activity in these behavioral studies.