Morphine-induced striatal dopamine efflux depends on the activity of nigrostriatal dopamine neurones

Abstract

It is clear that morphine markedly increases the turnover of dopamine (DA) in the rat striatum^1–3, although the nature of this increase remains obscure. The early suggestion, that morphine may block postsynaptic DA receptors in a similar manner to haloperidol⁴, has since been refuted^5,6. The effect of morphine on dopaminergic neurones seems to be presynaptic, but whether it stimulates^7,8 or inhibits^2,5 the functional activity of the dopaminergic neurones is unclear. We recently reported that morphine seems to have no effect on the functional activity of the nigrostriatal dopaminergic neurones, using the decline in DA after administration of α-methyl-p-tyrosine (αMT) as a measure of DA efflux^9,10. However, the substantia nigra and striatum are extremely rich in opiate receptors^11,12, and a considerable number of the striatal opiate receptors seem to be localised on dopaminergic nerve endings¹³; it would therefore be rather surprising if stimulation of these receptors by morphine did not alter the functional activity of the nigrostriatal dopaminergic neurones. To investigate this apparent discrepancy, we analysed the effect of morphine on DA efflux in conditions of altered impulse flow in the nigrostriatal dopaminergic neurones. The present results show that the administration of morphine results in increased efflux of DA from neurones with a lowered firing rate, but not from neurones with a normal or increased firing rate. Thus, morphine may be a modulator of the nigrostriatal dopaminergic neurones in that it counteracts decreasing dopaminergic activity, but has no effect when the activity is normal or increased.