3,4-dihydroxyphenylacetic acid (DOPAC) and the rat mesolimbic dopaminergic pathway: drug effects and evidence for somatodendritic mechanisms.

1 Drug effects on dopamine catabolism of the mesolimbic dopaminergic pathway have been investigated using a sensitive radioenzymatic assay for 3,4-dihydroxyphenylacetic acid (DOPAC). 2 Turnover of DOPAC was less rapid in the ventral tegmentum (containing somata and dendrites) than in the nucleus accumbens (containing nerve terminals): 9 and 115 ng g-1 min-1 for ventral tegmentum and nucleus accumbens respectively. 3 Reserpine (5 mg/kg, 1 h) elevated DOPAC concentration to a greater extent in ventral tegmentum than in nucleus accumbens. 4 Neuroleptic drugs elevated DOPAC levels in ventral tegmentum and nucleus accumbens. Thioridazine, sulpiride and clozapine, thought to act preferentially on the mesolimbic system, caused a similar elevation in both brain regions. 5 gamma-Butyrolactone (750 mg/kg) caused a significant decrease in the DOPAC concentration in ventral tegmentum after 0.5 and 1 h, while DOPAC levels in nucleus accumbens were not significantly altered at these time intervals. 6 Similarities exist between the dopamine catabolism in somatodendritic and nerve terminal regions of mesolimbic dopaminergic neurones in the response to neuroleptic drugs, but differences in catabolism are evident following certain pharmacological treatments such as reserpine and gamma-butyrolactone. 7 Dopamine release occurs in the somatodendritic region of mesolimbic dopaminergic neurones and release sites may be dendritic as has been found for nigrostriatal dopaminergic neurones.