Dopaminergic antagonists: effects of 1,2,3,4-tetrahydroisoquinoline and its N-methyl and N-propyl homologs on apomorphine- and L-dopa-induced behavioral effects in rodents

Abstract

N-Methyl-1,2,3,4-tetrahydroisoquinoline (MTIQ) antagonized apomorphine (APO)-induced stereotypy in a dose-related manner when injected i.p. in rats and attenuated L-dopa-induced hyperactivity in mice. 1,2,3,4-Tetrahydroisoquinoline (TIQ) and its homolog, N-n-propyl-, also blocked APO-induced stereotypy when given similarly. No significant difference was found between the amounts of radioactivity in the brain homogenates of MTIQ- and saline-pretreated rats after injection with [3H] APO. This suggested that MTIQ did not antagonize the behavioral effects of APO by blocking its entry into the brain. Mice fed ad libitum for 90 days with Purina Chow mixed with TIQ (5.0 mg/g) displayed behavioral supersensitivity in comparison with controls when injected with L-dopa (0.40 g/kg i.p.) after pretreatment with carbidopa. This was parallelled by a significant increase of dopamine-related adenylate cyclase activity measured in homogenates of caudate nuclei. The similarity between the behavioral effects induced by some neuroleptics and those observed with TIQ and its homologs suggests that the latter may be a new class of short-acting neuroleptics.