Electrophysiological characterization of substantia nigra dopaminergic neurons in partially lesioned rats: Effects of subthalamotomy and levodopa treatment

• Published in: Brain research Vol. 1084; no. 1; pp. 175 - 184
• Main Authors: Bilbao, Gaizka, Ruiz-Ortega, Jose Angel, Miguens, Natalia, Ulibarri, Isabel, Linazasoro, Gurutz, Gómez-Urquijo, Sonia, Garibi, Jesús, Ugedo, Luisa
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 21.04.2006; Amsterdam Elsevier; New York, NY
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Adrenergic Agents - toxicity; Adult and adolescent clinical studies; Animals; Apomorphine; Apomorphine - pharmacology; Biological and medical sciences; Brain Injuries - chemically induced; Brain Injuries - pathology; Brain Injuries - physiopathology; Brain Injuries - therapy; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine - metabolism; Dopamine Agents - administration & dosage; Dose-Response Relationship, Drug; Extracellular recording; Immunohistochemistry - methods; Levodopa - administration & dosage; Male; Medical sciences; Neurology; Neurons - drug effects; Neurons - physiology; Organic mental disorders. Neuropsychology; Oxidopamine - toxicity; Parkinson's disease; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; Responsiveness; Substantia Nigra - pathology; Subthalamic Nucleus - physiopathology; Subthalamic Nucleus - surgery; Tyrosine 3-Monooxygenase - metabolism; Tyrosine hydroxylase; Responsiveness; Tyrosine hydroxylase; Parkinson's disease; Extracellular recording; Apomorphine; Rat; Central nervous system; Electrophysiology; Parkinson disease; Tyrosine 3-monooxygenase; Characterization; Degenerative disease; Levodopa; Nervous system diseases; Enzyme; Rodentia; Antiparkinson agent; Extracellular; Cerebral disorder; Vertebrata; Mammalia; Locus niger; Treatment; Animal; Central nervous system disease; Dopaminergic neuron; Oxidoreductases; Lesion; Extrapyramidal syndrome
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.02.052

Progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta is the main histopathological characteristic of Parkinson's disease. We studied the electrophysiological characteristics of the spontaneous activity of substantia nigra pars compacta dopaminergic neurons in rats with a partial, unilateral, 6-hydroxydopamine lesion of the nigrostriatal pathway. In addition, the effects of subthalamotomy and prolonged levodopa treatment on the activity of dopaminergic neurons were investigated. As a result of the lesion (∼50% neuronal loss), the number of spontaneously active neurons was significantly reduced. Basal firing rate, burst firing and responsiveness to intravenously administered apomorphine remained unchanged. In contrast, the variation coefficient, a measure of interspike interval regularity, was significantly increased. Ibotenic acid (10 μg) lesion of the ipsilateral subthalamic nucleus in lesioned rats did not modify the electrophysiological parameters. However, prolonged levodopa treatment (100 mg/kg/day + benserazide 25 mg/kg/day, 14 days) reversed the irregularity observed in cells from lesioned rats, while it induced an irregular firing pattern in cells from intact rats. Our results using an experimental model of moderate Parkinson's disease indicate that surviving substantia nigra pars compacta dopaminergic neurons fire irregularly. In this model, subthalamotomy does not modify the firing pattern while levodopa treatment efficiently restores normal firing of SNpc neurons and does not appear to be toxic to them.