Serotonergic-dopaminergic interactions in the rat basal ganglia.

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Title Serotonergic-dopaminergic interactions in the rat basal ganglia.
Publication Type dissertation
School or College College of Pharmacy
Department Pharmacology & Toxicology
Author Liston, Dane Russell
Date 1981-06
Description The site of decarboxylation of L-DOPA to dopamine (DA) in patients with Parkinson's disease is unknown. Projections from the raphe nucleus containing 5-hydroxytryptamine (5-HT) may contribute to the production of DA from L-DOPA since these cells are known to contain L-aromatic amino acid decarboxylase. To test this hypothesis, rats were given a unilateral injection of 6-hydroxy-dopamine (6OHDA; 8 (mu)g in 4 (mu)l) into the substantia nigra. Ten to 12 days later animals were given L-DOPA: carbidopa (100mg/kg: 10mg/kg) or vehicle every 12 hrs for 8 injections and sacrificed 1-2 hrs after the last injection. Tyrosine hydroxylase (TH) activities and DA levels in the ipsilateral neostriatum were reduced to less than 5% of control in lesioned animals. The contralateral striata were not affected and served as controls. L-DOPA treatment did not significantly increase the striatal DA levels in lesioned animals. Additional neostriatal lesions induced by the serotonin neurotoxin, 5,7-dihydroxytryptamine (DHT; 16 (mu)g), did not significantly decrease DA levels below those found in animals with the 6OHDA lesions alone. Due to the failure of L-DOPA to increase striatal DA in animals with extensive 6OHDA lesions, it is concluded that 5-HT terminals in the striatum do not contribute significantly to the production of DA from L-DOPA in Parkinson's disease. During the course of these experiments it became apparent that DHT was altering dopaminergic function. Unilateral injection of DHT into the rat neostriatum markedly reduced not only striatal tryptophan hydorxylase (TPH) activity but also striatal tyrosine hydroxylase (TH) activity and dopamine (DA) levels measured 10-15 days later. The decrease in striatal TH activity was dose-related over the range of 8 to 32 (mu)g DHT; a dose of 16 (mu)g reduced TH activity to 40-50% of control, DA levels to 38% of control and TPH activity to 5-15% of control. Pretreatment of animals with amfonelic acid (15mg/kg), a selective DA uptake inhibitor, significantly reduced the effect of DHT to striatal TH activity and DA levels without affecting the DHT-induced decrease in TPH activity. Striatal choline acetyltransferase and glutamic acid decarboxylase activities were not decreased by 16 (mu)g DHT. The results indicate that DHT can compromise dopaminergic function in the rat neostriatum by damaging DA terminals in addition to its established neurotoxic effects on serotonin and nonrepinephrine terminals.
Type Text
Publisher University of Utah
Subject Physiology; Neurotoxins
Subject MESH Dihydroxytryptamines; Dopamine
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Serotonergic-dopaminergic interactions in the rat basal ganglia." Spencer S. Eccles Health Sciences Library. Print version of "Serotonergic-dopaminergic interactions in the rat basal ganglia." available at J. Willard Marriott Library Special Collection. QP 6.5 1981 L58.
Rights Management © Dane R. Liston.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,22442
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6g454tj
Setname ir_etd
ID 192654
Reference URL https://collections.lib.utah.edu/ark:/87278/s6g454tj
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