Abstract

The effects of systemic administration of β-phenylethylamine (β-PEA) and microiontophoretically applied β-PEA on the spontaneous discharge of dopamine (DA) neurons in the ventral tegmental area (VTA) of the anesthetized rat were examined. Intravenous administration of β-PEA (1.0, 2.5, and 5.0 mg/kg) and microiontophoretic applications of β-PEA caused inhibitory responses in DA neurons. Systemic administration and microiontophoretic applications of β-PEA induced dose- or current-dependent responses. The systemic β-PEA-induced inhibitory responses were reversed by pretreatment with the DA D₂ 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 β-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 β-PEA (100 μM) in the VTA via a microdialysis probe, and local application of β-PEA-stimulated somatodendritic DA release in the VTA. The β-PEA-induced release of DA was calcium ion-independent and was enhanced by pretreatment with pertussis toxin. These findings indicate that β-phenylethylamine inhibits DA neuron activity via DA D₂ autoreceptors in the rat VTA and that this inhibitory effect is mediated by the somatodendritic DA release.