Limbic pallidal adaptations following long-term cessation of dopaminergic transmission: lack of upregulation of dopamine receptor function

• Published in: Experimental neurology Vol. 186; no. 2; pp. 145 - 157
• Main Authors: Heidenreich, Byron A., Mitrovic, Igor, Battaglia, George, Napier, T.Celeste
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.2004; Elsevier
• Subjects: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine - pharmacology; 6-Hydroxydopamine; Action Potentials - drug effects; Animals; Benzazepines - pharmacology; Binding Sites; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Corpus Striatum - drug effects; Corpus Striatum - physiology; D 1 agonists; D 1 antagonists; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dopamine; Dopamine - metabolism; Dopamine - physiology; Dopamine Agonists - pharmacology; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Drug Administration Routes; Electrophysiology; Functional Laterality; Globus Pallidus - cytology; Globus Pallidus - drug effects; Globus Pallidus - physiology; Immunohistochemistry - methods; Injuries of the nervous system and the skull. Diseases due to physical agents; Iontophoresis - methods; Male; Medical sciences; Neurology; Neurons - classification; Neurons - drug effects; Neurons - physiology; Oxidopamine - toxicity; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1 - physiology; SCH23390; SKF38393; Sulpiride - pharmacology; Sympatholytics - toxicity; Synaptic Transmission - physiology; Time; Traumas. Diseases due to physical agents; Tyrosine 3-Monooxygenase - metabolism; Ventral pallidum; GPi; Dopamine; Ventral pallidum; DOPAC; 6-Hydroxydopamine; Electrophysiology; SCH23390; GP; 6-OHDA; D 1 antagonists; SKF38393; HVA; 5-HIAA; NE; D 1 agonists; VP; 5-HT; DA; GPe; HPLC-EC; Rat; Central nervous system; Pallidum; Encephalon; Dopaminergic transmission; Antagonism; Adaptation; Biological receptor; Dopamine receptor; Rodentia; Discharge pattern; D1 Dopamine receptor; Septum; Basal ganglion; D1 antagonists; Catecholamine; Long term; Vertebrata; Chronic; Sensitivity; Mammalia; Depletion; Neuron; Treatment; Chloral hydrate; Animal; Neurotransmitter; D1 agonists
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2003.11.004

Neurons in the ventral pallidum (VP) exhibit robust responding to activation of dopamine (DA) receptors of the D 1 class. To determine if the VP adapts to chronic cessation of DA transmission, the present studies examined D 1 receptor-mediated responses in the VP recorded extracellularly in chloral-hydrate anesthetized rats following destruction of DA neurons with 6-hydroxydopamine (6-OHDA) or long-term treatment with the D 1 antagonist SCH23390. Indices of basal spiking (i.e., spontaneous firing rate and pattern) recorded 10–21 days after unilateral 6-OHDA treatment did not differ from controls. Moreover, DA depletion did not alter the proportion of VP neurons whose rate was enhanced with iv injections of the D 1 agonist SKF38393, and the functional efficacy ( E max) and potency (ED 50) were similar to controls. There also was no change in the direction of responses, the E max or the ED 50 measure of sensitivity (ECur 50) to iontophoretic application of DA or SKF38393 in VP neurons. Forty-eight hours after 21 once-daily treatments with SCH23390, the number of [ 3H]SCH23390-labeled D 1 receptors was increased in the striatum, but unchanged in the VP, globus pallidus, or septum. Accordingly, there was no functional upregulation of VP responses to iv SKF38393. Indeed, the proportion of SKF38393-sensitive neurons was decreased after chronic SCH23390. Distinguishing the VP from other forebrain regions, these findings indicate that basal spiking is not altered in the VP following chronic DA depletion, and that no upregulation of VP DA receptor function occurs following either dopaminergic lesions or chronic antagonism of D 1 receptors.