Effects of dopaminergic stimulation on functional brain metabolism in rats with unilateral substantia nigra lesions

Wooten, G. Frederick; Collins, Ruth

doi:10.1016/0006-8993(83)90319-0

Cited by 70 publications

(28 citation statements)

References 24 publications

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“…D-amphetamine increased rCMR glc less on the lesioned than intact side in one study (Wooten & Collins, 1983), as we found with our k* responses, but results in other studies involving rCMR glc are inconsistent (Palacios & Wiederhold, 1985;Trugman & Wooten, 1987).…”

Section: Discussionsupporting

confidence: 85%

“…Consistent with our higher ipsilateral increments in k* following quinpirole, chronically lesioned rats show contralateral rotation (they turn away from the lesion) following quinpirole or apomorphine, a D 2 /D 1 -receptor agonist (Arnt & Hyttel, 1985;Ungerstedt, 1971;Wooten & Collins, 1983). On the other hand, consistent with the decreased ipsilateral increments in k* following D-amphetamine, lesioned rats given this drug show rotation towards the side of the lesion (Wooten & Collins, 1983). …”

Section: Discussionsupporting

confidence: 85%

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In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease

et al. 2007

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Parkinson's disease involves loss of dopamine (DA)-producing neurons in the substantia nigra, associated with fewer pre-synaptic DA transporters (DATs) but more post-synaptic dopaminergic D 2 receptors in terminal areas of these neurons.Hypothesis-Arachidonic acid (AA) signaling via post-synaptic D 2 receptors coupled to cytosolic phospholipase A 2 (cPLA 2 ) will be reduced in terminal areas ipsilateral to a chronic unilateral substantia nigra lesion in rats given D-amphetamine, which reverses the direction of the DAT, but will be increased in rats given quinpirole, a D 2 -receptor agonist.Methods-D-amphetamine (5.0 mg/kg i.p.), quinpirole (1.0 mg/kg i.v.), or saline was administered to unanesthetized rats having a chronic unilateral lesion of the substantia nigra. AA incorporation coefficients, k* (radioactivity/integrated plasma radioactivity), markers of AA signaling, were measured using quantitative autoradiography in 62 bilateral brain regions following intravenous [1-14 C]AA.Results-In rats given saline (baseline), k* was elevated in 13 regions in the lesioned compared with intact hemisphere. Quinpirole increased k* in frontal cortical and basal ganglia regions bilaterally, more so in the lesioned than intact hemisphere. D-amphetamine increased k* bilaterally but less so in the lesioned hemisphere.Conclusions-Increased baseline elevations of k* and increased responsiveness to quinpirole in the lesioned hemisphere are consistent with their higher D 2 -receptor and cPLA 2 activity levels, whereas reduced responsiveness to D-amphetamine is consistent with dropout of pre-synaptic elements containing the DAT. In vivo imaging of AA signaling using dopaminergic drugs can identify pre-and post-synaptic DA changes in animal models of Parkinson's disease.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 85%

In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease

et al. 2007

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“…In rats with unilateral SN, lesions, both apomorphine (a mixed D, and D, agonist) and L-DOPA (a precursor to dopamine) induce contralateral rotation and marked RCGU increases in the EP and SN, (up -200%) (Wooten and Collins, 1983;Trugman and Wooten, 1986). Electrophysiological studies have demonstrated that, in B-OHDAlesioned rats, systemically administered apomorphine profoundly and consistently inhibits the firing of identified SN, output neurons .…”

Section: Discussionmentioning

confidence: 99%

“…L-DOPA and apomorphine (a D, and D, agonist) produce indistinguishable RCGU patterns when administered systemically to rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra, a classical animal model of Parkinson's disease (Ungerstedt et al, 1973). This pattern is characterized by marked RCGU increases (-200%) in the entopeduncular nucleus (EP; homolog of the primate medial pallidum) and substantia nigra pars reticulata (SN,) ipsilateral to the nigral lesion, and moderates RCGU changes (-1 O-50%) in other brain regions (Wooten and Collins, 1983;Trugman and Wooten, 1986). It has been hypothesized that these profound glucose utilization changes in the EP and SN, reflect primarily increased physiological activity in the axon terminals of striatal projection neurons (Trugman and Wooten, 1986).…”

mentioning

confidence: 99%

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

Trugman¹,

Wooten²

1987

J. Neurosci.

153

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he relative roles of D1 and D2 dopamine receptor stimulation in mediating the antiparkinsonian effects of dopaminergic drugs remain unclear. To determine the functional metabolic consequences of selective dopamine receptor stimulation, we used 2-deoxyglucose (2-DG) autoradiography to examine the effects of the D1 agonist SKF-38393 and the D2 agonist LY-171555 on regional cerebral glucose utilization (RCGU) in rats with unilateral 6-hydroxydopamine (6-OHDA) substantia nigra lesions. SKF-38393 (0.5-25.0 mg/kg) and LY-171555 (0.01-5.0 mg/kg) produced indistinguishable behavioral responses, including vigorous contralateral rotation. Treatment with each drug similarly increased glucose utilization, dose-dependently, in the parafascicular thalamus, subthalamic nucleus, deep layers of the superior colliculus, and lateral midbrain reticular formation ipsilateral to the nigral lesion; glucose utilization was decreased in the ipsilateral lateral habenula. By contrast, the D1 and D2 agonists differentially altered glucose utilization in the entopeduncular nucleus (EP) and the substantia nigra pars reticulata (SNr). SKF-38393, 5.0 and 25.0 mg/kg, increased glucose utilization 127 and 275%, respectively, in the pars reticulata ipsilateral to the lesion. LY-171555, 1.0 and 5.0 mg/kg, caused maximal contralateral turning, yet did not alter glucose utilization in the ipsilateral SNr. The glucose utilization response of the ipsilateral EP paralleled that of the SNr demonstrating large increases following administration of SKF-38393 and minimal change following the use of LY-171555. The results demonstrate that the selective D1 agonist reproduces the marked glucose utilization increases (2-3-fold above control values) in the EP and SNr that were previously observed using L-DOPA and apomorphine in this model, whereas the selective D2 agonist does not.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Animals with severe dopamine depletion, as seen after bilateral administration of 6-hydroxydopamine, have to be fed via intragastric tube for a critical period after lesioning in order to survive (30,31 Reduced substance P expression together with the finding of normal enkephalin mRNA levels is consistent with the postulated role of the DlA receptor in activating the direct pathway. The changes in peptide levels are known to correspond to changes in the metabolic activity in these pathways, as measured with 2-deoxyglucose metabolism (38,39) and the induction of immediate early genes such as c-fos (40)(41)(42).…”

Section: Discussionmentioning

confidence: 99%

Altered striatal function in a mutant mouse lacking D1A dopamine receptors.

Drago

Gerfen

Lachowicz

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

322

266

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Of the five known dopamine receptors, DlA and D2 represent the major subtypes expressed in the striatum of the adult brain. Within the striatum, these two subtypes are differentially distributed in the two main neuronal populations that provide direct and indirect pathways between the striatum and the output nuclei ofthe basal ganglia. Movement The pivotal role played by dopamine receptors in the pathophysiology and treatment ofParkinson disease (1) and schizophrenia (2) and in the mode of action of addictive drugs such as amphetamine and cocaine (3, 4) is well established. Of the five known dopamine receptor subtypes (5), the DlA and D2 receptors account for the vast majority of dopamine receptors (6) expressed in the striatum. The DlA (also known as D, in the primate system) and D2 receptor subtypes are expressed mainly by spiny projection neurons, which account for 90-95% of the striatal neuron population (7). These striatal neurons may be subdivided into two major types on the basis of their axonal projections. One type provides a direct projection to the output nuclei of the basal ganglia: the substantia nigra and entopeduncular nucleus (the internal segment of the globus pallidus in primates). The other type provides projections to the globus pallidus (the external segment of the primate globus pallidus). As this latter type is connected indirectly to the output nuclei of the basal ganglia through connections with the subthalamic nucleus, the two output pathways are referred to as the direct and indirect output systems. Striatal neurons giving rise to the direct pathway express high levels of the DlA dopamine receptor subtype and the neuropeptides substance P and dynorphin, whereas neurons giving rise to the indirect pathway express high levels of the D2 dopamine receptor and the peptide enkephalin (7). The levels of peptide expression in these neurons provide an assay oftheir activity (7), as neuropeptide levels correlated with fuing rates in target neurons (1).Current models suggest that imbalanced activity in the direct and indirect pathways is responsible for clinical movement disorders (8). A number of studies have demonstrated that dopamine oppositely effects these two output pathways through their differential expression ofthe DlA and D2 receptors (7). For example, depletion of striatal dopamine with lesions of the nigrostriatal dopamine pathway in animal models of Parkinson disease results in reduced expression of substance P in direct output neurons and increased enkephalin expression in indirect striatal output neurons. Moreover, these changes may be selectively reversed with selective dopamine receptor agonist treatments, so that D1 agonist treatment normalizes substance P levels whereas D2 agonist treatment normalizes enkephalin levels (9). While these studies have demonstrated the differential role of DlA and D2 receptors in striatal function, important questions concerning the interaction between these neuronal pathways remain. To provide an experimental animal model to address the...

show abstract

Effects of dopaminergic stimulation on functional brain metabolism in rats with unilateral substantia nigra lesions

Cited by 70 publications

References 24 publications

In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease

In vivo imaging of disturbed pre- and post-synaptic dopaminergic signaling via arachidonic acid in a rat model of Parkinson's disease

Selective D1 and D2 dopamine agonists differentially alter basal ganglia glucose utilization in rats with unilateral 6-hydroxydopamine substantia nigra lesions

Altered striatal function in a mutant mouse lacking D1A dopamine receptors.

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