Inhibition and facilitation of motor responding of the mouse by actions of dopamine agonists in the forebrain

Abstract

The actions of dopamine and agonists of dopamine to influence forebrain structures and modify spontaneous locomotion of the mouse were studied, firstly, by injecting agents from different chemical series into the nucleus accumbens (phenylethylamine, aporphine, benzo[g]quinoline, tetralin, dopamine, N-n-propyl- N-phenethyldopamine, N-n-propyl- N-butyldopamine, apomorphine, trans-N-n-propyl-6, 7- and -7,8-dihydroxyoctahydrobenzo[g]quinoline, 2-di- n-propylamino-5,6- and -6,7-dihydroxytetralin, 2-di-ethylamino-5,6-dihydroxytetralin) and, secondly, by selecting a potent agent (2-di- n-propylamino-5,6-dihydroxytetralin) for injection into 43 other forebrain areas. Agents from all chemical series were shown to reduce locomotor activity on injection into the nucleus accumbens. The most effective agents were the dialkylated tetralin derivatives and the N-propyl benzo[g]quinoline compound (0.025–0.5 μg); inhibition of motor activity generally decreased as dose was increased. The inhibitory effects on motor activity of the propyl substituted tetralin and [g]quinoline were specifically antagonised by sulpiride and/or spiperone (prazosin, yohimbine and methysergide were ineffective). Injections of tetralin (0.1 μg) not only into the nucleus accumbens but also into the tuberculum olfactorium, septal nucleus, anterior olfactory nucleus, anteromedial fibre system, claustrum and caudate-putamen could effect inhibition of motor activity. Generally, injections away from these structures were ineffective. It is suggested that small doses of dopamine and agonists of dopamine can influence dopamine receptors which are sensitive to neuroleptic drugs (presynaptic in limbic and striatal regions, but with a possibility of postsynaptic involvement in cortical regions) to effect inhibition of motor activity from a number of discrete areas of the forebrain of the mouse.