Responsiveness to 'autoreceptor' doses of apomorphine inversely correlated with the firing rate of dopaminergic A9 neurons: action of baclofen

Abstract

Supersensitivity of dopamine (DA) autoreceptors develops soon after acute treatments with baclofen or gamma-butyrolactone, two drugs which suppress DA neuronal firing. We have hypothesized that this effect might reflect a condition associated with the low firing rate of DA cells induced by such treatments rather than a long-term adaptive modification of DA receptor sensitivity. In this study we show that the degree of the intravenous apomorphine-induced inhibition of A9-DA neurons is inversely correlated to the basal firing rate of these neurons. When administered after baclofen, apomorphine further reduced DA cell activities in a manner proportional to the predrug firing rate, as in control rats. Since the minute doses of apomorphine which were used are thought to selectively activate DA autoreceptors, our finding may indicate that DA autoreceptor stimulation is more effective when the activity of the DA neurons is low, or it is decreased by drugs such as baclofen.