Subcortical excitatory amino acid levels after acute and subchronic administration of typical and atypical neuroleptics

Abstract

The effects of three atypical neuroleptic compounds, clozapine, sulpiride, and (−)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine ((−)-3-PPP) were compared to the effects of haloperidol and saline on excitatory amino acid levels in the rodent nucleus accumbens and corpus striatum after acute (1 day) and subchronic (28 days) treatment. Equivalent doses of each drug were determined by assessing their in vivo displacement of [ 3H]spiperone binding in the nucleus accumbens and corpus striatum. After acute treatment, all three atypical neuroleptics, but not haloperidol, produced a significant decrease in nucleus accumbens glutamate concentrations. Acute haloperidol treatment significantly elevated glutamate concentrations in the corpus striatum when compared to all three atypical drugs. After subchronic treatment, (−)-3-PPP significantly increased glutamate concentrations in the nucleus accumbens when compared to the effects of haloperidol and clozapine. There were no major between-group differences in glutamate levels after subchronic treatment in the corpus striatum. The effects of acute and subchronic neuroleptic administration on aspartate levels in the nucleus accumbens and corpus striatum were highly variable. These findings indicate that atypical and typical neuroleptics may alter subcortical excitatory amino acid levels in a site-specific manner.