Comparison of the effects of dopamine D1 and D2 receptor antagonists on rat striatal, limbic and nigral dopamine synthesis and utilisation.

Abstract

The effects of dopamine (DA) antagonists upon DA synthesis and utilisation in the rat striatum, olfactory tubercle and substantia nigra have been studied. The concentrations of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the rate of depletion of DA after in vivo inhibition of tyrosine hydroxylase by H44/68, and the accumulation of L-DOPA after in vivo inhibition of l-aromatic amino acid decarboxylase by NSD 1015 were measured in the study. Haloperidol (0.23 mumol/kg i.p.), sulpiride (293 mumol/kg i.p.) and remoxipride (5.6 mumol/kg i.p.) increased both DA synthesis and utilisation in the striatum and olfactory tubercle. A lower dose of sulpiride (45 mumol/kg i.p.) increased DA synthesis and utilisation in the olfactory tubercle alone. None of the compounds, at the doses used, affected either DOPAC and HVA concentrations or the rate of utilisation of DA in the substantia nigra. Sulpiride (293 mumol/kg i.p.) and remoxipride, however, produced a modest rise in nigral DA synthesis. The dopamine D 1-selective antagonist SCH 23390 had only modest effects on striatal, limbic and nigral DA synthesis and utilisation at the doses tested (0.078 and 0.36 mumol/kg i.p.).