Interactions of nigrostriate synaptic transmission, iontophoretic O-methylated phenethylamines, dopamine, apomorphine and acetylcholine.

Recordings were made from, and drugs applied to, neurons in the caudate nucleus of unanesthetized cats, using multibarrel micropipette electrodes. The substantia nigra was stimulated by sterotactically placed electrodes. Three O-methylated derivatives of dopamine, meta-methoxyphenethylamine (m-MPEA), para-methosy-phenethylamine (p-MPEA) and 3,4-demethoxyphenethylamine (DIMPEA), inhibited most, excited a few, and had no detectable effect on a substantial number of the cells upon which they were tested. A statistically significant correlation was found between the effects of dopamine (DA) and the three O-methylated derivatives on the same populations of cells. Iontophoretic release of the O-methylated derivatives could not prevent the actions of DA, nor could it block synaptically mediated effects of the nigrostriate pathway. It is concluded that the three O-methylated products are partial agonists of DA. The findings are difficult to reconcile with the suggestion that the experimental parkinsonian-like symptoms caused by O-methylated phenethylamines are the consequence of blockade of dopaminergic synapses. No correlation, negative or positive, was found between the effects of DA and of acetylcholine (ACh). The findings do not support the theory that balanced sets of antagonistic synapses, one dopaminergic, the other cholinervic, operate upon individual neurons in the caudate nucleus. Apomorphine and dopamine were shown to have similar effects on a substantial number of neurons, even though the onset and offset of the effect of apomorphine were slower than those of DA. This observation agrees with the suggestion that some of the central effects of apomorphine are due to an action at dopaminoceptive receptor sites.