Effects of drugs on regional brain concentrations of dopamine and dihydroxyphenylacetic acid
Umezu, K.; Moore, K.E.
Journal of Pharmacology and Experimental Therapeutics 208(1): 49-56
1979
ISSN/ISBN: 0022-3565 PMID: 32385 Document Number: 140890
A radioenzymatic assay sensitive to less than 1 ng of dopamine and dihydroxyphenylacetic acid (DOPAC) was developed and employed to measure the effects of several drugs on the quantities of these compounds in the striatum, olfactory tubercle, hypothalamus and median eminence, regions which contain the terminals of nigrostriatal, mesolimbic, incertohypothalamic and tuberoinfundibular dopaminergic neurons, respectively. Pretreatment of rats with a monoamine oxidase inhibitor (pargyline) increased dopamine and decreased DOPAC concentrations in all brain regions. Neuroleptics (haloperidol, thioridazine) did not alter the dopamine concentrations in any brain region, but increased DOPAC concentrations in the striatum, olfactory tubercle and hypothalamus, but not in the median eminence. Three days of treatment with estradiol benzoate did not alter dopamine or DOPAC concentrations in any brain region. Reserpine markedly reduced the dopamine concentration in all 4 brain regions; it also caused a prolonged increase in the concentration of DOPAC in the striatum, transient increases in the olfactory tubercle and hypothalamus, but was without effect on DOPAC concentrations in the median eminence. Since treatment with neuroleptics and estradiol, which have been shown to increase the .alpha.-methyltyrosine-induced decline of dopamine in the median eminence, are without effect on DOPAC concentrations in this brain region, it is suggested that changes in concentrations of this metabolite cannot be used to estimate the activity of tuberoinfundibular dopaminergic neurons.