Inhibitory effects of trace amines on rat midbrain dopaminergic neurons

Trace airlines are biological compounds that are still awaiting identification of their role in neuronal function. Using intracellular electrophysiological recordings. we investigated the depressant action of two trace amines (beta-phenylethylamine and tyramine) on the firing activity of dopaminergic neurons of the substantia nigra pars compacta and ventral tegmental area. This inhibition was due to a membrane hyperpolarisation that was blocked by the D2 dopamine receptor antagonist sulpiride and was not potentiated by the dopamine-uptake blocker, cocaine. Inhibition of the dopamine transporter did not mediate the effects of trace airlines. because unlike cocaine, trace airlines did not potentiate the inhibitory responses to exogenously applied dopamine. The inhibitory actions of beta-phenylethylamine and tyramine were present in reserpine-treated animals but were abolished when the dopamine-synthesis inhibitor carbidopa was applied. Our data suggest that trace amines cause an indirect activation of dopamine autoreceptors. by all increased efflux of newly synthesised dopamine. The inhibition of dopaminergic activity by trace airlines may relate to their involvement in neuronal processes linked to drug addiction, schizophrenia, attention deficit hyperactive disorders and Parkinson's disease. (C) 2003 Elsevier Ltd. All rights reserved.