Buspirone is an anxiolytic drug with a clinical potency similar to that of diazepam, but it lacks affinity for diazepam of γ-aminobutyric acid (GABA) binding sites. Because previous reports suggested that buspirone may possess dopamine (DA) agonist activity, buspirone was tested for effects of DA neurotransmission. At presynaptic DA receptors, unlike other DA agnostis, buspirone inhibited neither synaptosomal tyrosine hydroxylase activity nor the in vivo γ-butyrolactone-induced activation of striatal tyrosine hydroxylase. However, buspirone did inhibit the action of apomorphine, a direct acting DA agonist in both of these DA autoreceptor test systems with a potency similar to that of chlorpromazine. Striatal DA synthesis and metabolism were markedly increased by buspirone treatment; the maximum effective dose was 3.0 mg/kg, s.c., which caused a 400% increase. Extracellular single cell recordings showed that buspirone, administered intravenously, markedly increased substantia nigra DA neuronal impulse flow and potently reversed inhibition of DA cell impulse flow caused by systemic injection of apomorphine (5 to 10 μg/kg). Inhibition of DA cell impulse flow by iontophoresis of DA was reversed by iontophoretic administration of buspirone, but buspirone did not interfere with the ability of GABA to inhibit DA impulse flow. That buspirone interacts with receptor sites in addition to the DA autoreceptor was indicated by the finding that after DA receptor blockade with haloperidol, buspirone further enhanced DA neuronal impulse flow. Buspirone did not cause catalepsy and did not inhibit apomorphine-induced turning in rats with unilateral 6-hydroxydopamine lesions of the substantia nigra, which indicated that the drug has minimal action at the classical postsynaptic DA receptor. These data suggest that (a) buspirone enhances DA neuronal activity, in part, by weakly inhibiting presynaptic DA receptors, and (b) buspirone has minimal effects on postsynaptic DA receptors.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Neuroscience|
|State||Published - Jun 2 1983|
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