Neurochemical effects of buspirone, a novel psychotropic drug, on the central cholinergic system

Abstract

Buspirone, a novel psychotropic anxioselective agent, produced a dose-dependent decrease in the level of acetylcholine in the striatum of the rat. The maximum effect of about 25-30% was produced at the dose of 20 mg kg-1. A smaller decrease of 10% was also found in the n. accumbens-olfactory tubercle while other brain regions were unaffected. The drug did not alter striatal choline acetyltransferase or acetylcholinesterase activities and was feeble in displacing [3H]dexetimide from its specific muscarinic binding sites. The effect of buspirone in lowering acetylcholine content was more marked and longer lasting in the striatum of female than male rats. Buspirone proved to be weak as a blocker of the dopamine receptor agonist, apomorphine, and it appears that only a small proportion of the decrease in striatal acetylcholine content can be attributed to the blockade of dopamine receptors. Rapid homologous tolerance to an acute challenge with buspirone on striatal acetylcholine was achieved within seven days of its chronic administration, and, unlike clozapine, a cross tolerance of buspirone to chronic haloperidol treatment was also observed. Other data indicating that the drug differed from haloperidol both qualitatively and quantitatively on dopaminergic neurochemical parameters, and the fact that it is not cataleptogenic, suggest that buspirone cannot be considered a typical neuroleptic agent. The possibility that buspirone may act as an agonist at certain presynaptic dopamine receptors, which could translate into a fall in striatal acetylcholine content, is discussed.

Comparative neuropharmacology of buspirone and MJ-13805, a potential anti-anxiety drug

“…We have observed a near significant decrease in frontal cortical 5-HT metabolism 90 rain after 1.0mg/kg s.c. buspirone (unpublished observation). However, similar to Kolasa et al (1982), we failed to observe an LSD-like serotonin syndrome (c(. Jacobs, 1976) at a 10 mg/kg dose as reported by Hjorth and Carlsson (1982), with either buspirone or MJ-13805 regardless of route of injection.…”

Comparative chronic effects of buspirone or neuroleptics on rat brain dopaminergic neurotransmission

“…The site or mechanism for these effects have yet to be elucidated. As buspirone apparently modulates the extrapyramidal system differently from previously described drugs, is not anti-cholinergic (Riblet et aL, 1982;Kolasa et al, 1982) and does not alter GABA neurotransmission Sanghera and German, 1983), these effects are not readily explainable. Opposite to other anti-anxiety drugs, buspirone causes a small increase in locus coeruleus noradrenergic activity (Sanghera et al, 1982).…”

Neuropharmacology of Buspirone

“…Without direct interaction with choliner gic receptor systems [14,23], buspirone has been shown to enhance the behavioral effects of the cholinergic agonists arecoline and oxotremorine (cholinergically induced catalepsy) at doses which decrease striatal acetylcholine levels [6], These data are summarized in table VIII.…”

“…Ncurochcmically, buspirone increases striatal levels of the dopamine me tabolites homovanillic acid and dihydroxy-phenylacetic acid [14,17], It appears to act preferentially as a presynaptic dopamine an tagonist. In the striatum, where dopamine autoreceptors have been identified, buspirone increases tyrosine hydroxylase activity.…”