Effects of buspirone on brain indoleamines and catecholamines in wild-typemice and Lurcher mutants

The effects of a chronic serotoninergic stimulation on brain monoamine leve ls and metabolism were studied in wild-type (+/+) mice and Lurcher (Lc/+) m utants. Endogenous serotonin, dopamine, noradrenaline and some of their maj or metabolites were measured in the frontal cortex, neostriatum, thalamus, brainstem, cerebellum and spinal cord. In +/+ mice, buspirone (1 mg/kg; i.p .) treatment during 40 days increased indoleamines, albeit with moderate ch anges in the ratios between tissue serotonin metabolites and endogenous ser otonin, augmented noradrenaline contents in the spinal cord, and caused ele vations of dopamine metabolites in most regions. In Lc/+ mutants, the effec ts of buspirone were attenuated, but higher L-tryptophan and indoleamine le vels, suggest a storage of serotonin in a non-releasable compartment. In th e hypoplastic Lc/+ cerebellum, indoleamine content was accrued, but with a decreased [serotonin metabolites]/[serotonin] ratio, indicating that the re organized nerve terminals in Lc/+ mutants although they call synthesize and accumulate serotonin, may not utilize it efficiently in synaptic transmiss ion. (C) 2000 Elsevier Science B.V. All rights reserved.