A comparative study of the effects of prostaglandins and d-amphetamine on the metabolism of 3H-dopamine continuously presented to rat brain in vivo.

Unanesthetized rats with chronic indwelling cannulas, engaged in food reinforced operant behavior, were infused intracerebroventricularly with a solution containing a trace concentration of 3H-dopamine (3H-DA) with or without prostaglandins (PGs). Approximately 45 minutes after the infusion was started, the procedure was changed to a push-pull perfusion. Perfusate from the ventricles contained significant quantities of the 3H-DA metabolites 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 (3H-NA) metabolite 3H-3-methoxy-4-hydroxy-phenylethyleneglycol (3H-MHPG). The presence of PGF2 alpha decreased the amount of 3H-DOPAC, 3H-HVA, and 3H-3-MT in perfusate, while PGE1 had the opposite effects. d-Amphetamine (0.5 mg/kg, 1P) affected the recovery of these metabolites from perfusate in a manner similar to PGF2 alpha and opposite to PGE1. PGF2 alpha and the highest (seizure-inducing) dose of PGE1 significantly decreased, while d-amphetamine significantly increased, the quantity of 3H-MHPG in perfusate. Therefore, PGs affect central dopaminergic and noradrenergic activity in vivo, as reflected by changes in their metabolic profiles, and may play a role in the response of the central nervous system to drugs which act through catecholaminergic mechanisms.