Selective reduction in dopamine turnover in the rat frontal cortex and hypothalamus during withdrawal from repeated cocaine exposure.

The effects of 7 days repeated cocaine administration on the dynamics of dopamine release and metabolism in four rat brain regions (frontal cortex, hypothalamus, nucleus accumbens and striatum) were evaluated 1 week (long-term effects) after the final cocaine injection. 3-Methoxytyramine and 3,4-dihydroxyphenylacetic acid (DOPAC) rates of formation were respectively used to assess the dynamics of dopamine release and metabolism. Consistent with a previous report, cocaine withdrawal was associated with marked reductions in DOPAC rate of formation in the frontal cortex and hypothalamus but not in the nucleus accumbens or the striatum. Dopamine release as indicated by 3-methoxytyramine steady-state concentration and its rate of formation was normal in all four brain regions 1 week after repeated cocaine exposure. The ratios of 3-methoxytyramine rate of formation to that of DOPAC were calculated and found to be increased in the frontal cortex and hypothalamus suggesting dopamine reuptake inhibition, at least 1 week after cocaine withdrawal, continued to be depressed in these regions. It is concluded that repeated cocaine has no long-term effect on dopamine release but produces selective long-term reductions in dopamine turnover in frontal cortex and hypothalamus. Cocaine withdrawal is therefore better associated with changes in dopamine turnover than with its release.