Behavioral effects in rats following intrastriatal microinjection of manganese

We have demonstrated that injection of manganese into one caudate nucleus in rats results in a predominant ipsilateral turning behavior, accompanied at higher doses by an intermittent, alternating and dose-related incidence of contralateral turning and stereotypies. Although the pharmacological evidence produced (effect of alpha-MT, L-DOPA, pargyline) indicates a definite participation of the dopaminergic system in the latter two phenomena, it is probable that ipsilateral turning is the result of involvement of other transmitter systems as well. Tegmental serotoninergic and intrastriatal cholinergic pathways appear to be involved in the production of the basic postural asymmetry resulting in turning. The amount of interference with the nigrostriatal and mesolimbic dopaminergic pathways may determine the speed of circling, and the concurrent inhibition of locomotion. This is more evident with bilateral injections. Manganese appears to act at presynaptic levels within the striatum by blocking release of the transmitter, thus creating a localized, relative deficit in caudate function. The end result is the release of the dominant "ipsilateral syndrome-inducing system' from its inhibitory control. Repeated or chronic administration of this metal in man or animals is known to result in a brain dopamine and/or serotonin deficit commensurate with the clinical manifestations of bradykinesia and dystonia. Our results are compatible with the anatomical findings of Poirier and collaborators and tend to support the dual ipsilateral and contralateral syndrome-inducing systems in the caudate postulated by Cools, and the complementary roles of dopamine, serotonin and acetylcholine within that nucleus. No one transmitter is involved alone in the experimental production of the manganese syndrome, or of its component symptoms.