Metabolism of 3H-dopamine continuously perfused through push-pull cannulas in rats' brains: modification by amphetamine or prostaglandin F2 alpha.

Using perfusion cannulas implanted in the lateral cerebroventricles, the metabolism of a trace concentration of 3H-dopamine, continuously presented, was investigated in rats performing an operant for food reinforcement. The subjects were mature, drug-naive, male Long-Evans rats. Perfusate contained measurable quantities of 3H-3,4-dihydroxyphenylacetic acid (3H-DOPAC), 3H-3-methoxy-4-hydroxyphenylacetic acid (3H-homovanillic acid, 3H-HVA), 3H-3-methoxytyramine (3H-3-MT) and the 3H-noradrenaline metabolite, 3H-3-methoxy-4-hydroxyphenylethyleneglycol (3H-MHPG). Systemic injection of d-(1.5 mg/kg) or 1-(3.0 mg/kg) amphetamine resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate with a concurrent decrease in fixed-ratio 20 behavior. Addition of prostaglandin F2 alpha (10 ng/microliters perfused at a rate of 10 microliters/minute) had no effect on the rats' fixed-ratio 20 behavior or rectal temperature, but resulted in decreased quantities of 3H-DOPAC, 3H-HVA and 3H-MHPG in perfusate. It is concluded that this methodology allowed us to monitor drug-induced changes in CNS dopaminergic and noradrenergic function in conscious rats engaged in schedule-controlled operant behavior. Furthermore, a trace concentration of PGF2 alpha in perfusion medium caused changes in 3H-dopamine metabolism in a manner similar to that of systemically administered amphetamines.