Absence of tolerance to antiaggressive activity of methadone after chronicadministration to male mice

We have examined the effects of methadone (2 and 5 mg/kg, i.p), acutely or chronically administered for 30 consecutive days, on agonistic interactions between male mice. Individually housed mice were confronted with anosmic ' standard opponents' in a neutral area 30 min after the last drug administra tion, These encounters were videotaped and the accumulated time allocated b y subjects to 10 broad behavioural categories was estimated using an etholo gically based analysis. After acute treatment, methadone (5 mg/kg) signific antly decreased offensive behaviours (threat and attack), as compared with the control group (P < 0.01), although with a weak (but significant) increa se in immobility (P < 0.05). No tolerance to methadone antiaggressive activ ity was apparent after repeated administration of the drug. On the contrary , the action on immobility showed a clear tolerance development with repeat ed injections. Med Sci Res 27:285-287 (C) 1994 Lippincott Williams & Wilkin s.