title: Regulation of polysynaptic subthalamonigral transmission by D2, D3 and D4 dopamine receptors in rat brain slices.
abstract: Dopamine depletion in experimental models of Parkinson's disease promotes burst firing of neurons in the subthalamic nucleus (STN) and substantia nigra zona reticulata (SNR). A synaptically generated form of burst firing has been shown to arise from complex excitatory postsynaptic currents (EPSCs) that are evoked in SNR neurons by STN stimulation. The present experiments were designed to characterize actions of dopamine on complex EPSCs in slices of rat brain. Using patch pipettes to record whole-cell currents under voltage clamp, dopamine (30 μm) caused a reversible 64% reduction in complex EPSC charge. This effect was partially mimicked by D(2), D(3) and D(4) receptor agonists, and the action of dopamine could be nearly completely blocked by the combined effects of the D(2/3) antagonist sulpiride and the D(4) antagonist L-745,870. Local application of dopamine to the STN caused a larger inhibition of the complex EPSC (55% reduction) than did dopamine application to the SNR (15% reduction). Simple, monophasic EPSCs, which were evoked in SNR neurons by stimulating the SNR close to the recording pipette, were inhibited to a smaller extent compared to complex EPSCs. Bursts of action potentials evoked in SNR neurons by STN stimulation were inhibited by dopamine to a greater extent than was spontaneous firing. These results show that dopamine D(2)-like receptors inhibit complex EPSCs and burst discharges in the SNR by acting within the STN to suppress transmission in the subthalamonigral pathway. Dopamine receptor-mediated inhibition of polysynaptic connections in the STN might be beneficial in the treatment of Parkinson's disease.
authors.affiliation: Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
authors.forename: Ke-Zhong
authors.initials: KZ
authors.lastname: Shen
authors.forename: Steven W
authors.initials: SW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D015259:Dopamine Agents; D011954:Receptors, Dopamine; D004298:Dopamine