Abstract

The goal of this competitive renewal is to understand the effects of dopamine on cells in the substantia nigra pars reticulata, a primary output nucleus of the basal ganglia.
Four specific aims with a total of 12 experiments are outlined: The experiments outlined under Aim 1 will selectively activate D1 and/or D2 receptors in the striatum of the rat. Recordings will reveal the effects on discharge in the SNr, and behavioral studies will evaluate the overall effects in the intact awake rat.
Aim 2 will attempt to determine differential effects of the direct versus indirect pathways from striatum to SNr. Basically the same set of experiments as proposed under Aim 1 will be repeated in rats with lesions of the subthalamic nucleus, which should eliminate influences of the indirect pathway on SNr.
Aim 3 will use the same striatal stimulation paradigm as Aim 1, but local blockade of D1 and/or D2 receptors within SNr will also be made. Thus the effects of local receptor blockade on SNr discharge and behavior will be evaluated.
Specific Aim 4 will determine whether or not nigral or pallidal projecting neurons in the striatum express functional D2 receptors. The study will utilize patch-clamp recordings on dissociated striatal neurons that have been prelabeled by retrograde transport of fluorescent beads. The patch clamp electrode will contain the D2 agonist quinpirole so that D2 activated channels will be detected.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023541-08
Application #
2037227
Study Section
Neurology B Subcommittee 2 (NEUB)
Program Officer
Oliver, Eugene J
Project Start
1986-09-01
Project End
1998-11-30
Budget Start
1996-12-01
Budget End
1997-11-30
Support Year
8
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
Northeastern University
Department
Other Health Professions
Type
Schools of Pharmacy
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Zahr, Natalie May; Martin, Lynn Pauline; Waszczak, Barbara Lee (2004) Subthalamic nucleus lesions alter basal and dopamine agonist stimulated electrophysiological output from the rat basal ganglia. Synapse 54:119-28
Waszczak, Barbara L; Martin, Lynn P; Finlay, Heather E et al. (2002) Effects of individual and concurrent stimulation of striatal D1 and D2 dopamine receptors on electrophysiological and behavioral output from rat basal ganglia. J Pharmacol Exp Ther 300:850-61
Waszczak, B L; Martin, L; Boucher, N et al. (2001) Electrophysiological and behavioral output of the rat basal ganglia after intrastriatal infusion of d-amphetamine: lack of support for the basal ganglia model. Brain Res 920:170-82
Hinerth, M A; Collins, H A; Baniecki, M et al. (2000) Novel in vivo electrophysiological assay for the effects of cocaine and putative ""cocaine antagonists"" on dopamine transporter activity of substantia nigra and ventral tegmental area dopamine neurons. Synapse 38:305-12
Martin, L P; Jackson, D M; Wallsten, C et al. (1999) Electrophysiological comparison of 5-Hydroxytryptamine1A receptor antagonists on dorsal raphe cell firing. J Pharmacol Exp Ther 288:820-6
Waszczak, B L; Martin, L P; Greif, G J et al. (1998) Expression of a dopamine D2 receptor-activated K+ channel on identified striatopallidal and striatonigral neurons. Proc Natl Acad Sci U S A 95:11440-4
Martin, L P; Waszczak, B L (1996) Dopamine D2, receptor-mediated modulation of the GABAergic inhibition of substantia nigra pars reticulata neurons. Brain Res 729:156-69
Martin, L P; Waszczak, B L (1994) D1 agonist-induced excitation of substantia nigra pars reticulata neurons: mediation by D1 receptors on striatonigral terminals via a pertussis toxin-sensitive coupling pathway. J Neurosci 14:4494-506
Liu, J C; Cox, R F; Greif, G J et al. (1994) The putative dopamine D3 receptor agonist 7-OH-DPAT: lack of mesolimbic selectivity. Eur J Pharmacol 264:269-78
Cox, R F; Waszczak, B L (1993) Inhibition of substantia nigra dopamine cell firing by R(-)-N-n-propylnorapomorphine: electrophysiological and autoradiographic studies after regional inactivation of dopamine receptors by microinjection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline. Brain Res 613:32-42

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