Effect of intracaudate drug injections on the striatal syndrome in reserpinized cats

Abstract

Reduction of striatal dopaminergic activity was pharmacologically duplicated in cats by pretreatment with reserpine, 0.5 mg/kg i.p., which resulted in progressively increasing motor signs of hypokinesia, rigidity, catatonia and tremor. A simple method of quantitatively scoring the extrapyramidal symptoms showed maximum and stable disability 18 hr after pretreatment with reserpine and intracaudate or systemic injection of various drugs known to influence striatal function was done at this time. Of the drugs injected in caudate, apomorphine 50 and 100 µg completely reversed reserpine-induced motor signs, while dopamine (DA), L-DOPA, d-amphetamine, atropine and amantadine significantly reduced various aspects of the extrapyramidal symptoms. However, L-DOPA demonstrated almost complete reversal of extrapyramidal symptoms when given systemically rather than after direct injection into the caudate nucleus. At equiactive doses, clonidine antagonized only reserpine-induced eye changes without significantly influencing extrapyramidal symptoms, while 5-hydroxytryptamine (5-HT), pyribenzamine, physostigmine and tremorine were ineffective. EMG assessment of rigidity and polygraphic recording of EEG and tremor together with neurochemical analysis of caudate nucleus DA levels, following apomorphine and dopamine in reserpinized cats, provides supporting evidence for apomorphine's activating role on DA receptors in the striatum.