Chronic systemic administration of amphetamine increases food intake to morphine, but not to U50-488H, microinjected into the ventral tegmental area in rats

Chronic intermittent administration of amphetamine (AMPH) sensitizes rats to the stimulatory effects on feeding produced by systemic injections of either morphine (MORPH) or the kappa-opiate receptor agonist, U50,488H (U50). Both morphine and the putative kappa-receptor endogenous ligand, dynorphin, have been reported to stimulate feeding when administered into the ventral tegmental area (VTA). To evaluate whether the VTA is the site where AMPH produces sensitization to the feeding effects of opiates, rats were given daily IP injections of either saline or AMPH (3 mg/kg). The amount of powdered food ingested during the 5 h following the injections was measured. After 9 days of AMPH or saline administration, twice weekly tests were begun of the effects of either saline, MORPH (1-10 nmol) or U50 (10 pmol to 10 nmol) injected into the VTA; AMPH administration was continued on intervening days. MORPH produced a statistically significant greater increase in food intake in rats chronically treated with AMPH than in saline treated rats. No statistically significant effects were produced by U50. However, when U50 was administered systemically to the same animals, food intake increased, and the effect was significantly greater in the AMPH-pretreated group. Thus the sensitization to the feeding effects of MORPH and U50 produced by chronic AMPH administration appears to involve different systems; the mesolimbic dopamine system appears to mediate sensitization to the effects of the predominately mu-receptor agonist, MORPH, but not of the kappa-receptor agonist, U50.