SYNTHESIS OF DOPAMINE AND 5-HT IN ANATOMICAL REGIONS OF THE RATS BRAIN IS UNAFFECTED BY SUSTAINED INFUSION OF AMPEROZIDE

The 5-HT2A antagonist, amperozide, is considered to be a potentially useful drug for the treatment of substance abuse. The effects of this drug on the Sprague-Dawley rat were examined on the synthesis of dopamine and serotonin (5-HT) as well as on the intakes of food and water and the level of body weight. Amperozide was delivered subcutaneously by osmotic minipump in doses of 2.5 mg/kg or 5.0 mg/kg per day for 7 days. After injection of 100 mg/kg NSD-1015, each brain was dissected post mortem into midbrain, pens, hypothalamus, septum, nucleus accumbens, striatum, frontal cortex and the hippocampus. Neither concentration of amperozide altered the synthesis of dopamine or 5-HT, as measured in terms of the formation of 1-3,4-dihydroxyphenylalanine (L-DOPA) and 5-hydroxytryptophan (5-HTP), respectively, in any of the 8 brain regions analyzed. Both doses of amperozide reduced food intake by 20% within 24 hr after implantation of the pumps, but feeding resumed postoperatively at the control level within 48 hr. Amperozide affected neither the intake of water nor the level of body weight. The lack of effect on the synthesis of dopamine and 5-HT and the absence of side effects on the intakes of food and water suggest that amperozide may be a specific agent for suppressing alcohol drinking.