The role of opioid mechanisms in the anorectic effects of stimulants: U50,488H enhances amphetamine inhibition of free feeding in rats.

The influences of the kappa-opiate agonist U50,488H (U50; 4 mg/kg IP), the neuroleptic haloperidol (HAL; 0.3 mg/kg IP), and MK-801 (0.2 mg/kg IP), a noncompetitive antagonist for NMDA receptors, were compared on the effects of nine days of d-amphetamine (AMPH) treatment (3 mg/kg IP) on food and water intake and urine output. AMPH prevented feeding stimulation produced by U50 during the first 2 h, whereas U50 inhibited the hyperphagic phase that rats showed between 2 and 5 h after AMPH administration. Tolerance did not develop to the first 2-h suppression of feeding; in contrast, the late hyperphagic phase slowly recovered across the nine days of treatment. Combined administration of the two drugs barely affected water intake but considerably increased urine output. Unlike U50, HAL left the late hyperphagic response to AMPH unchanged and delayed the development of hyperdipsia. In our study MK-801 had one effect only: It significantly reduced amphetamine diuresis. These results suggest that by inhibiting the late hyperphagic response U50 enhances the anorectic effects of AMPH, but that dopamine probably has no direct role in this interaction.