Effects of beta-Phenylethylamine on Dopaminergic Neurons of the Ventral Tegmental Area in the Rat:A Combined Electrophysiological and Microdialysis Study

摘要

The effects of systemic administration of beta-phenylethylamine (beta-PEA) and microiontophoretically applied beta-PEA on the spontaneous discharge of dopamine (DA) neurons in the ventral tegmental area (VTA) of the anesthetized rat were examined.Intravenous administration of beta-PEA (1.0,2.5,and 5.0 mg/kg) and microiontophoretic applications of beta-PEA caused inhibitory responses in DA neurons.Systemic administration and microiontophoretic applications of beta-PEA induced dose- or current-dependent responses.The systemic beta-PEA-induced inhibitory responses were reversed by pretreatment with the DA D_2 receptor antagonists haloperidol (0.5 mg/kg i.p.) and sulpiride (10 mg/kg i.p).Pretreatment with reserpine (5 mg/kg i.p.24 h earlier) did not completely block the systemic administration of beta-PEA (2.5 mg/kg) inhibition.A microdialysis study of freely moving rats demonstrated that the extracellular DA level increased significantly in response to local application of beta-PEA (100 n-M) in the VTA via a microdialysis probe,and local application of beta-PEA-stimulated somatodendritic DA release in the VTA.The beta-PEA-induced release of DA was calcium ion-independent and was enhanced by pretreatment with pertussis toxin.These findings indicate that beta-phenylethylamine inhibits DA neuron activity via DA D_2 autoreceptors in the rat VTA and that this inhibitory effect is mediated by the somatodendritic DA release.