THE POTENTIATION OF CORTICAL NEURON RESPONSES TO NORADRENALINE BY 2-PHENYLETHYLAMINE IS INDEPENDENT OF ENDOGENOUS NORADRENALINE

2-Phenylethylamine (PE) is an endogenous brain amine which produces sy mpathomimetic responses and potentiates cortical neuron responses to n oradrenaline (NA). In order to examine further the mechanism of action of PE, extracellular recordings were made of the activity of single n eurones in the cerebral cortex in urethane-anesthetized rats. Sympatho mimetic responses to PE were blocked by pretreatment with reserpine, r eserpine pius alpha-methyl-p-tyrosine and desipramine. It is concluded that the sympathomimetic responses to PE are indirect. 2-Phenylethyla mine potentiated cortical neuron responses to electrical stimulation o f the locus coeruleus in a dose-dependent manner. This was seen when P E was given systemically (with as little as 1 mug/kg) and iontophoreti cally. The effects of PE were not reproduced by its metabolite phenyla cetic acid or its putative metabolite phenylethanolamine. Iontophoreti c applications of PE (0-6 nA, 2-5 minutes) potentiated cortical neuron responses to iontophoretically applied NA, without affecting the spon taneous firing rate, or the responses to iontophoretically applied GAB A or acetylcholine. This effect of PE was not blocked by pretreatment with alpha-methyl-p-tyrosine or desipramine, and was potentiated by pr etreatment with reserpine and reserpine plus alpha-methyl-p-tyrosine. It is probable that the ability of PE to modulate neuronal responses t o NA does not involve the presynaptic NA terminal or endogenous NA and it is likely that PE acts directly to increase the efficacy of NA. Th ese findings are consistent with the hypothesis that the physiological role of PE is to modulate catecholaminergic transmission within the c entral nervous system.