An ethopharmacological assessment of the effects of methadone on agonistic interactions in male mice

Although the antiaggressive properties of several opiates are known, the action of methadone on agonistic interactions has not been explored. In this study, we examined the effects of a single injection of methadone (0.5-20 mg kg(-1), i.p.) on the agonistic behaviour elicited by isolation in male mice. Individually housed mice were confronted with anosmic `standard opponents' in a neutral area 30 min after drug administration. The encounters were videotaped and the accumulated time allocated by subjects to ten broad behavioural categories was estimated using an ethologically based analysis. Methadone (1 and 2.5 mg kg(-1)) significantly increased threat behaviours, as compared with the saline group (p < 0.05). The intermediate dose (5mg kg(-1)) decreased time spent in threat and attack (p < 0.02), with a weak increase in immobility (p < 0.1). The largest doses (10, 15, 20 mg kg(-1)) diminished offensive behaviours (p < 0.02), but increased defence/submission and immobility (p < 0.02). In conclusion, methadone exhibits a complex ethopharmacological profile characterised by a rise in aggression at low doses, a suppression of aggression at intermediate doses, and a non-selective decrease in offensive behaviours at high doses.