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.
Footnotes
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The work was supported by the Showa Pharmaceutical University.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.084764.
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ABBREVIATIONS: β-PEA, β-phenylethylamine; DA, dopamine; VTA, ventral tegmental area; HPLC, high-performance liquid chromatography; PTX, pertussis toxin; RM-ANOVA, repeated measurement analysis of variance.
- Received February 8, 2005.
- Accepted April 6, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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