D-pipecolyl-leucyl-glycinamide, a substituted tripeptide analogue of the C-terminal part of oxytocin, influences tolerance to and dependence on ethanol in mice.

The effects of graded doses of a substituted tripeptide analogue of the C-terminal part of oxytocin, D-Pip-Leu-GlyNH2 (DPLG), were investigated on the development of tolerance to the hypothermic effect of and dependence on alcohol in mice. Ethanol injection (4 g/kg i.p.) repeated on 3 consecutive days led to the development of tolerance in control and peptide-treated (0.005 microgram/mouse) animals. In the latter group, however, the level of tolerance was lower than in the control animals. The higher doses (0.05-5.0 micrograms/mouse) inhibited the development of tolerance. Repeated peptide administrations (5, 25, 125 micrograms/animal) did not affect the development of the dependence on alcohol which resulted from combined daily injections of tert-butanol (1.5 g/kg i.p.) and ethanol (3 g/kg i.p.). The severity of withdrawal was quantified via the convulsions induced with different doses of picrotoxin. When the peptide was injected only before the testing of withdrawal, DPLG markedly prolonged the onset of withdrawal signs.