title: Subthalamic nucleus lesions alter basal and dopamine agonist stimulated electrophysiological output from the rat basal ganglia.
abstract: The subthalamic nucleus (STN) is an important link in the "indirect" striatal efferent pathway. To assess its role on basal ganglia output via the substantia nigra pars reticulata (SNr), we monitored the single unit activities of SNr neurons in chloral hydrate-anesthetized rats 5-8 days after bilateral kainic acid lesions (0.75 microg/0.3 microl/side) of the STN. Consistent with loss of an excitatory input, the average basal firing rate of SNr neurons was significantly reduced in STN-lesioned animals. Moreover, the lesions modified the responses of SNr neurons to individual and concurrent stimulation of striatal D1 and D2 receptors. Bilateral striatal infusions of the D1/D2 agonist apomorphine (10 microg/microl/side) into the ventral-lateral striatum (VLS) were previously shown to cause significant increases in SNr cell firing (to 133% of baseline) in normal rats. However, in STN-lesioned rats, identical infusions caused no overall change in SNr activity (mean, 103% of basal rates). Conversely, selective stimulation of striatal D2 receptors by bilateral co-infusion of the D2 agonist quinpirole and the D1 antagonist SCH 23390 that previously caused little change in SNr firing in normal rats significantly inhibited their firing in STN-lesioned rats. Finally, the modest excitatory responses of SNr neurons to selective stimulation of striatal D1 receptors by co-infusions of SKF 82958 with the D2 antagonist YM09151-2 were not altered by lesions of the STN. These results implicate the STN as a mediator of excitatory response of SNr neurons to D2, and mixed D1/D2, dopamine receptor agonists in normal rats, and challenge conventional views on the role of the STN and the "indirect" pathway in regulating dopamine-stimulated output from the SNr.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences, Northeastern University, Boston, Massachusetts 02115, USA.
authors.forename: Natalie May
authors.initials: NM
authors.lastname: Zahr
authors.forename: Lynn Pauline
authors.initials: LP
authors.lastname: Martin
authors.forename: Barbara Lee
authors.initials: BL
authors.lastname: Waszczak
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001479:Basal Ganglia / Q000166:cytology* / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D001927:Brain Diseases / Q000503:physiopathology; D001931:Brain Mapping; D002452:Cell Count / Q000379:methods; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020531:Subthalamic Nucleus / Q000293:injuries* / Q000473:pathology
chemical_list: D001549:Benzamides; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D001058:Apomorphine; C030265:nemonapride