REGIONAL DISTRIBUTION OF 5-HT TRANSPORTERS IN THE BRAIN OF WILD-TYPE AND PURKINJE-CELL DEGENERATION MUTANT MICE - A QUANTITATIVE AUTORADIOGRAPHIC STUDY WITH [H-3]CITALOPRAM

The neurological mutant 'Purkinje cell degeneration' (pcd) is characte rized by a primary degeneration of Purkinje cells, as well as by retro grade and secondary partial degeneration of cerebellar granule cells a nd inferior olivary neurons, and can be considered as an animal model of human degenerative ataxias. The serotonin (5-HT) innervation was ex amined in wild type and pcd mice, by quantifying 5-HT uptake sites, or transporters, using [H-3]citalopram blinding autoradiography. In both wild type and pcd mutants, the highest densities of 5-HT transporters were in mesencephalic and rostral pontine regions, in limbic structur es, in hypothalamus and in discrete thalamic divisions, while the lowe st labelling was found in cerebellum and brainstem reticular formation . In pcd mice, although [H-3]citalopram labelling was higher in cerebe llar cortex and deep cerebellar nuclei, when binding densities were co rrected for surface area, the up-regulation of 5-HT transporters was p resent only in deep cerebellar nuclei. Also, higher labelling was foun d in nuclei raphe dorsalis :and medialis, in ventral divisions of rost ral neostriatum, caudal neostriatum, rostral globus pallidus, posterom edial amygdaloid nucleus, septum, olfactory tubercles, vertical limb o f Broca's diagonal band, periventricular, latero-ventral and medio-ven tral thalamic nuclei, medial geniculate nucleus, anterior hypothalamus and entorhinal cortex. The results indicate a relative integrity of t he 5-HT innervation, but with a reorganization of serotoninergic termi nals in the cerebellum, in particular in the deep cerebellar nuclei. T his suggests that in progressive cerebellar degeneration, as found in the pcd mutant, the modified 5-HT system may still participate in moto r functions by exerting an overall modulation of excitatory amino acid neurotransmission, but the availability of 5-HT may be altered in def ined brain targets, as is the case for other spontaneous cerebellar mu tants, in particular for the 'Lurcher' mutant mouse, a model of human olivopontocerebellar atrophy. (C) 1998 Elsevier Science B.V. All right s reserved.