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.