Brain homovanillic acid: regional changes over time with antipsychotic drugs

Acute administration of equivalent doses of either chlorpromazine, thioridazine, or clozapine, respectively, produced progressively smaller increases in brain homovanillic acid (HVA) in the rabbit; however, changes in HVA in three brain regions were of equal magnitude for a single dose of a given drug. Chronic administration of fluphenazine enanthate resulted in a decrease in HVA relative to acute treatment in caudate more than limbic regions. No differences between caudate and limbic regions were observed during daily chlorpromazine administration for 3 ro 8 days. Tolerance appeared to develop in approximately 1 week. Chronic treatment with clozapine produced no tolerance at one week but suggestive evidence of tolerance in caudate and limbic regions at two weeks. No tolerance was observed in the hypothalamus during chronic treatment with any drug used. Cisternal CSF HVA paralleled caudate HVA during acute and chronic treatments.