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

Abstract

The effects of a chronic serotoninergic stimulation on brain monoamine levels and metabolism were studied in wild-type (+/+) mice and Lurcher ( Lc/+) mutants. Endogenous serotonin, dopamine, noradrenaline and some of their major 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 changes in the ratios between tissue serotonin metabolites and endogenous serotonin, augmented noradrenaline contents in the spinal cord, and caused elevations of dopamine metabolites in most regions. In Lc/+ mutants, the effects of buspirone were attenuated, but higher l-tryptophan and indoleamine levels, suggest a storage of serotonin in a non-releasable compartment. In the hypoplastic Lc/+ cerebellum, indoleamine content was accrued, but with a decreased [serotonin metabolites]/[serotonin] ratio, indicating that the reorganized nerve terminals in Lc/+ mutants although they can synthesize and accumulate serotonin, may not utilize it efficiently in synaptic transmission.