Opposite effects of ibotenic acid and 6-hydroxydopamine lesions of the lateral hypothalamus on intracranial self-stimulation and stimulation-induced locomotion

Abstract

The purpose of the present study was to test the respective roles of the intrinsic neurons and of the catecholaminergic fibers in two behaviors elicited by electrical stimulation of the lateral hypothalamus, intracranial self-stimulation and the increase in locomotor activity produced by noncontingent stimulation. One group of rats was unilaterally injected in the middle lateral hypothalamus with a dose of ibotenic acid known to significantly decrease self-stimulation (4 gmg/0.5 gml). Two other groups received, in the same area, an injection of a small dose of 6-hydroxydopamine (2μg/0.5 μl). The rats of one of these groups were pre-treated with desmethylimipramine. Two other groups of rats were respectively injected with the vehicle of each neurotoxin. Eight days later all rats were bilaterally implanted with stimulation electrodes, one in the lesioned area, the other in the contralateral region. Each electrode of each animal was tested first for self-stimulation, then for locomotor activation measured in the open field produced by non-contingent stimulation. Whatever the lesion or the behavior tested, the response of the lateral hypothalamus contralateral to the lesioned area was normal. Self-stimulation was disturbed only with stimulation of the lateral hypothalamus lesioned by ibotenic acid. Self-stimulation in the lateral hypothalamus lesioned by 6-hydroxydopamine was normal. However, a significant loss of noradrenaline in the hippocampus and of dopamine in the striatum was observed. Furthermore, the brains of two rats unilaterally injected with the usual dose of 6-hydroxydopamine were processed for tyrosine hydroxylase immunocytochemistry. The results showed that the organization of the catecholaminergic fibers was totally disrupted by the lesion, although a residual labeling was observed in the injection site. Conversely, the locomotor increase elicited by the non-contingent stimulation was normal in the lateral hypothalamus lesioned by ibotenic acid but was abolished by stimulation of the same area lesioned by 6-hydroxydopamine, whether rats were pre-treated or not with desmethylimipramine. These data suggest that in the lateral hypothalamus intracranial self-stimulation and induced locomotor activation are supported by different neuronal substrates.