The effect of d-amphetamine and haloperidol alone and in combination on milk drinking in rats

The effects of d-amphetamine (0.5-4.0 mg/kg IP) and haloperidol (0.015-1.0 mg/kg IP) alone and in combination on intake of a sweetened milk solution were determined in rats. Experimental sessions consisted of a 15-min access to the milk solution once a day, 7 days a week. d-Amphetamine was administered 15 min prior to the session and haloperidol was administered 60 min prior to the session. The interaction of these compounds was determined by repeated determination of the dose-response function for d-amphetamine in combination with different doses of haloperidol. When given alone, each drug produced a dose-dependent decrease in milk intake. In combination with haloperidol, the decrement caused by d-amphetamine was shifted to lower doses in a dose-dependent manner. Isobolographic analysis of the interaction indicates that the intermediate doses (0.03-0.06 mg/kg) of haloperidol were additive and the highest doses (0.12-0.25 mg/kg) of haloperidol were infraadditive with d-amphetamine. Dose-dependent neuropharmacological actions of these compounds may account for dose-dependent interactions.