Alterations in serotonin receptors in the neostriatum of weaver mutant mice

Abstract

Mice that carry the autosomal recessive gene weaver show a distinctive loss of nigrostriatal dopamine innervation, with the greatest deficits in the dorsal caudate-putamen and almost complete sparing in the nucleus accumbens and ventral caudate. In addition to loss of dopamine in this model, it has recently been shown that markers of serotonin (5-hydroxytryptamine, 5-HT) innervation including 5-HT content, synaptosomal uptake of [3H]5-HT and [3H]citalopram binding were elevated in the dorsal neostriatum of the weaver mutant mouse. Using quantitative autoradiography of specific ligands for dopamine and 5-HT uptake sites as well as serotonin 5-HT1 and 5-HT2A receptors, we found an increased density of 5-HT uptake sites and 5-HT1 receptors restricted to the dorsal portion of the neostriatum of the weaver mouse. In contrast, 5-HT2A receptors were increased in both the dorsal and ventral portions of the rostral neostriatum as well as the nucleus accumbens. The behavioural and functional relevance of these receptor changes is unclear, although, adaptations in 5-HT may play a role in certain aspects of spontaneous behaviour in the weaver mutant mouse.