EFFECTS OF BUSPIRONE AND ITS METABOLITE, 1-(2-PYRIMIDINYL)PIPERAZINE, ON BRAIN MONOAMINES AND THEIR METABOLITES IN RATS

  • 1 January 1989
    • journal article
    • research article
    • Vol. 248  (1) , 50-56
Abstract
Buspirone, an anxiolytic drug with selective affinity for the 5-HT-1A subtype of serotonin receptors, caused a dose-related decrease in 5-hydroxyindole acetic acid (5-HIAA) concentration in rat hypothalamus after doses of 1 to 10 mg/kg s.c. The decrease in 5-HIAA concentration after a 3 mg/kg s.c. dose of buspirone persisted at 4 hr but not at 7 hr. The decrease was due apparently to a reduced turnover of serotonin; the accumulation of 5-hydroxytryptophan after decarboxylase inhibition was also suppressed by buspirone, not only in hypothalamus but also in brain stem, hippocampus and striatum. 1-(2-Pyrimidinyl)-piperazine (1-PP), a major metabolite of buspirone, did not affect hypothalamic 5-HIAA concentration at doses up to 10 mg/kg s.c. Both buspirone and 1-PP increased hypothalamic concentrations of 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) sulfate, the norepinephrine metabolite, the effect being more pronounced with 1-PP but occurring after doses as low as 0.3 mg/kg s.c. with each compound. The increase in MHPG sulfate concentration persisted for at least 4 hr after a 3 mg/kg s.c. dose of each compound. The increase in MHPG sulfate produced by buspirone may have been due partly to 5-HT-1A receptor activation, inasmuch as other serotonin agonists have been found to cause a similar increase. 1-PP is reported to lack affinity for 5-HT-1A receptors so its elevation of MHPG sulfate concentration may have resulted from alpha-2 receptor blockade. The increase in MHPG sulfate concentration after buspirone injection may have been due at least partly of formation to the metabolite, 1-PP. Buspirone also increased whole brain concentrations of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, and increased the accumulation of dopa in striatum after decarboxylase inhibition. 1-PP had little effect on the concentration of the dopamine metabolites. The action of 1-PP may be mainly blockade of alpha-2 receptors, whereas buspirone alters serotonin and dopamine metabolism probably by activation of 5-HT-1A receptors and blockade of D2 autoreceptors, respectively.

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