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Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output.
J Pharmacol Exp Ther. 1994 Dec; 271(3):1434-43.JP

Abstract

To examine the role of D1 dopamine receptors in modulating basal ganglia output and how this role may be altered by changes in dopaminergic transmission, the effects of a D1 dopamine agonist on firing rates of substantia nigra pars reticulata (SNpr) neurons were determined in reserpine-treated rats and compared with effects observed in nigrostriatal-lesioned and normal rats. It was confirmed that systemic administration of the D1 dopamine agonist SKF 38393 (10 mg/kg i.v.) induces a small (averaging 20% above base line) increase in firing rates of SNpr neurons in normal rats and significantly inhibits SNpr single unit activity in rats studied 6 to 26 weeks after 6-hydroxydopamine (6-OHDA)-induced substantia nigra dopamine cell lesion. In contrast to results obtained after 6-OHDA lesions, SKF 38393 administration consistently and significantly increased the firing rates of SNpr neurons in rats treated for 6 days with reserpine (1 mg/kg/day s.c.); increases averaged 88% above base line. Five days after the 6-day reserpine treatment was discontinued, administration of SKF 38393 still induced a pronounced increase in SNpr activity. These increases were reversed by the administration of the D1 dopamine antagonist SCH 23390. SKF 38393 also significantly increased the firing rates of a subpopulation of SNpr neurons in rats treated with only a single dose of reserpine (10 mg/kg s.c. 4-7 hr). The difference between responses in reserpine and 6-OHDA-treated rats was not due to the shorter time course of the reserpine treatments, as SKF 38393 did not consistently affect the activity of SNpr neurons 7 days after 6-OHDA nigral dopamine cell lesion. When the subchronic reserpine treatment was administered to rats lesioned previously with 6-OHDA, D1 dopamine agonist-mediated inhibition of SNpr neuronal activity was obtained. The results show that SNpr responses to D1 dopamine agonist administration after reserpine treatment are enhanced ("supersensitive") relative to normal, whereas SNpr responses to D1 dopamine agonists in animals with 6-OHDA-induced dopamine cell degeneration are opposite to those observed in normal and in reserpinized animals. Current models of basal ganglia function predict that D1 dopamine agonists should reduce activity in the SNpr, because D1 dopamine receptors on striatonigral neurons are thought to stimulate striatonigral firing rates and to enhance the release of tau-aminobutyric acid in the SNpr. The present results call for modification of these concepts.

Authors+Show Affiliations

Neurophysiological Pharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7996456

Citation

Huang, K X., and J R. Walters. "Electrophysiological Effects of SKF 38393 in Rats With Reserpine Treatment and 6-hydroxydopamine-induced Nigrostriatal Lesions Reveal Two Types of Plasticity in D1 Dopamine Receptor Modulation of Basal Ganglia Output." The Journal of Pharmacology and Experimental Therapeutics, vol. 271, no. 3, 1994, pp. 1434-43.
Huang KX, Walters JR. Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output. J Pharmacol Exp Ther. 1994;271(3):1434-43.
Huang, K. X., & Walters, J. R. (1994). Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output. The Journal of Pharmacology and Experimental Therapeutics, 271(3), 1434-43.
Huang KX, Walters JR. Electrophysiological Effects of SKF 38393 in Rats With Reserpine Treatment and 6-hydroxydopamine-induced Nigrostriatal Lesions Reveal Two Types of Plasticity in D1 Dopamine Receptor Modulation of Basal Ganglia Output. J Pharmacol Exp Ther. 1994;271(3):1434-43. PubMed PMID: 7996456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrophysiological effects of SKF 38393 in rats with reserpine treatment and 6-hydroxydopamine-induced nigrostriatal lesions reveal two types of plasticity in D1 dopamine receptor modulation of basal ganglia output. AU - Huang,K X, AU - Walters,J R, PY - 1994/12/1/pubmed PY - 1994/12/1/medline PY - 1994/12/1/entrez SP - 1434 EP - 43 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 271 IS - 3 N2 - To examine the role of D1 dopamine receptors in modulating basal ganglia output and how this role may be altered by changes in dopaminergic transmission, the effects of a D1 dopamine agonist on firing rates of substantia nigra pars reticulata (SNpr) neurons were determined in reserpine-treated rats and compared with effects observed in nigrostriatal-lesioned and normal rats. It was confirmed that systemic administration of the D1 dopamine agonist SKF 38393 (10 mg/kg i.v.) induces a small (averaging 20% above base line) increase in firing rates of SNpr neurons in normal rats and significantly inhibits SNpr single unit activity in rats studied 6 to 26 weeks after 6-hydroxydopamine (6-OHDA)-induced substantia nigra dopamine cell lesion. In contrast to results obtained after 6-OHDA lesions, SKF 38393 administration consistently and significantly increased the firing rates of SNpr neurons in rats treated for 6 days with reserpine (1 mg/kg/day s.c.); increases averaged 88% above base line. Five days after the 6-day reserpine treatment was discontinued, administration of SKF 38393 still induced a pronounced increase in SNpr activity. These increases were reversed by the administration of the D1 dopamine antagonist SCH 23390. SKF 38393 also significantly increased the firing rates of a subpopulation of SNpr neurons in rats treated with only a single dose of reserpine (10 mg/kg s.c. 4-7 hr). The difference between responses in reserpine and 6-OHDA-treated rats was not due to the shorter time course of the reserpine treatments, as SKF 38393 did not consistently affect the activity of SNpr neurons 7 days after 6-OHDA nigral dopamine cell lesion. When the subchronic reserpine treatment was administered to rats lesioned previously with 6-OHDA, D1 dopamine agonist-mediated inhibition of SNpr neuronal activity was obtained. The results show that SNpr responses to D1 dopamine agonist administration after reserpine treatment are enhanced ("supersensitive") relative to normal, whereas SNpr responses to D1 dopamine agonists in animals with 6-OHDA-induced dopamine cell degeneration are opposite to those observed in normal and in reserpinized animals. Current models of basal ganglia function predict that D1 dopamine agonists should reduce activity in the SNpr, because D1 dopamine receptors on striatonigral neurons are thought to stimulate striatonigral firing rates and to enhance the release of tau-aminobutyric acid in the SNpr. The present results call for modification of these concepts. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7996456/Electrophysiological_effects_of_SKF_38393_in_rats_with_reserpine_treatment_and_6_hydroxydopamine_induced_nigrostriatal_lesions_reveal_two_types_of_plasticity_in_D1_dopamine_receptor_modulation_of_basal_ganglia_output_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7996456 DB - PRIME DP - Unbound Medicine ER -