Quantitative analysis of [3H]spiroperidol binding to rat forebrain sections: Plasticity of neostriatal dopamine receptors after nigrostriatal injury

Neve, Kim A.; Altar, C. Anthony; Wong, Catherine; Marshall, John F.

doi:10.1016/0006-8993(84)91280-0

Cited by 89 publications

(28 citation statements)

References 22 publications

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“…Thus, the early and persistent behavioral deficits are consistent with the observation that animals with less than 5-10% of their terminals remaining in the striatum are not able to maintain normal extracellular DA levels even in the presence of enhanced neuronal processes (Robinson and Whishaw 1988;Zhang et al 1988;Abercrombie et al 1990;Castañeda et al 1990;Parsons et al 1991;Robinson et al 1994). Furthermore, even in the presence of enhanced neuronal processes and supersensitive postsynaptic receptors, these animals do not recover from their behavioral deficits (Zigmond and Stricker 1973;Creese and Snyder 1979;Marshall 1979Marshall , 1984Neve et al 1982Neve et al , 1984. Thus, even though the nigrostriatal DA system shows resiliency in response to massive insult, a critical number of DA nerve terminals appears to be required for behavioral recovery to occur.…”

Section: Discussionsupporting

confidence: 77%

“…However, Robinson et al (1994) have shown that normalization of the extracellular concentration of DA, which is the net result of several processes (synthesis, release, uptake and diffusion), occurs gradually over three to four weeks. In addition, when DA depletion exceeds 85%, compensatory post-synaptic receptor supersensitivity develops several weeks after the lesion in response to reduced extracellular DA levels (Neve et al 1982(Neve et al , 1984Zigmond and Stricker 1980). Thus, some combination of increased availability of DA and increased sensitivity to the transmitter may explain the behavioral recovery.…”

Section: Discussionmentioning

confidence: 99%

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Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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Overt symptoms of Parkinson's disease do not manifest themselves until there is a substantial loss of the dopaminergic nigrostriatal projection. However, as neuroprotective strategies are developed, it will be essential to detect the disease in its preclinical phase. Performance on conditioned reaction time tasks is known to be impaired by extensive 6-hydroxydopamine-induced lesions of theThe primary neuropathology of Parkinson's disease is the loss of dopamine (DA) neurons within the substantia nigra (SN) and massive depletion of DA in the striatum, the terminal region of the SN. This loss of DA appears to be responsible for the most prominent symptoms of Parkinson's disease. The degree of neurological deficit is related to the loss of striatal DA (Hornykiewicz and Kish 1987). The neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), used extensively to induce selective loss of DA neurons within the SN, provide animal models that share several of the characteristics of Parkinson's disease (see reviews by Zigmond and Keefe 1997;Jenner and Marsden 1986;Gerlach and Riederer NO . 6 Bilateral 6-OHDA on Reaction Time 7571996; Przedborski and Jackson-Lewis 1998). In addition, whereas intrastriatal injection of indirect DA agonists induces stereotypy (Costall et al. 1973;Statton and Solomon 1984), 6-OHDA lesions of the striatum block this stereotyped behavior (Price and Fibiger 1974). Finally, chronic administration of DA receptor antagonists produce extrapyramidal effects reminiscent of Parkinson's disease, and this is believed to be due to their action at D 2 receptors located in the striatum (Coffin et al. 1989). Although resting tremor and muscular rigidity are generally not reported in rodents after pharmacological manipulation of the nigrostriatal pathway, deficits in movement initiation and execution have been studied using several tests including a conditioned reaction time task. In this task, animals are typically required to respond in a particular way and within a limited period in order to receive a reward, such as a food pellet. This behavioral paradigm is responsive to pharmacological manipulation of dopaminergic neurotransmission mediated by the D 2 subtype of DA receptors Koob 1987, 1989;Amalric et al. 1993Amalric et al. , 1995Smith et al. 2000). For example, we have shown that low dose blockade of D 2 receptors, but not D 1 or D 3 receptors, decreased correct responses in the conditioned reaction time task, increased delayed responses, and lengthened reaction time in a manner suggestive of dysfunctions in movement initiation (Amalric et al. 1993;Smith et al. 2000). Moreover, deficits in reaction time have also been reported in Parkinson's disease (Evarts et al. 1981;Gauntlett-Gilbert and Brown 1998;Berry et al. 1999). These deficits appear to be mediated by the nigrostriatal dopaminergic pathway, as 6-OHDA-induced loss of SN neurons and striatal DA, and not accumbal DA, produces impairments in this task (Amalric and Koob 1987), and intrastriatal infusion...

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Smith

Amalric²,

Koob

et al. 2002

Neuropsychopharmacology

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“…It has long been known that 6-OHDA lesions which cause extensive DA depletion result in D, receptor proliferation (Creese and Snyder, 1979;Neve et al, 1984), and, until recently (Bennett and Wooten, 1986;Breese et al, 1987), there was near-uniform agreement on this point (see Seeman, 1980, for review). Of particular relevance to the present results are previous findings indicating the D, receptor proliferation occurs primarily within the lateral striatal area (Savasta et al, 1987b), from which our recordings were obtained.…”

Section: -----------------------I 1oo ------------------------I Imentioning

confidence: 92%

Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation

et al. 1990

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Extracellular single unit recording and microiontophoretic techniques were used to determine the sensitivities and interactions of D1 and D2 dopamine (DA) receptors in the caudate putamen (CPu) of rats that were denervated of DA by intraventricular injections of the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA). Seven to 10 d after the 6-OHDA injection, DA levels in the ipsilateral CPu were reduced to 11.8% of control. Current-response curves revealed that the inhibitory responses of CPu neurons to microiontophoretic administration of both the selective D1 receptor agonist SKF-38393 and the selective D2 receptor agonist quinpirole were significantly increased in 6-OHDA-pretreated rats, suggesting up-regulation of both receptor subtypes. Although our previous studies have established that D1 receptor activation is normally required for (enables) the inhibitory effects of selective D2 agonists in the CPu, this requirement was no longer evident in 6-OHDA- denervated rats. Whereas acute DA depletion [produced by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine (AMPT)] attenuated the inhibitory effects of quinpirole on CPu neurons, long-term DA denervation (produced by 6-OHDA) enhanced the inhibitory effects of the D2 agonist. The enhanced effects of quinpirole in 6-OHDA-lesioned rats were not due to residual DA stimulating supersensitive D1 receptors (i.e., enabling) since further DA depletion (99.7%), produced by acute administration of AMPT in 6-OHDA-lesioned rats, failed to diminish the inhibitory efficacy of quinpirole. In addition to relieving D2 receptors from the need for D1 receptor-mediated enabling, 6-OHDA lesions also abolished the normal synergistic relationship between the receptor subtypes since low (subinhibitory) currents of SKF-38393 (4 nA) failed to potentiate the inhibitory effects of quinpirole on CPu neurons in lesioned rats. Similar findings (i.e., supersensitivity and loss of synergistic effects) were obtained from rats that had received repeated pretreatment with reserpine (2.5 mg/kg) for 4 d, indicating that these effects of 6-OHDA lesions were due to the depletion of synaptic DA rather than to the structural loss of DA terminals. Therefore, both the quantitative (potentiation) and the qualitative (enabling) synergistic effects between D1 and D2 receptors in the rat CPu were abolished when these receptors were functionally supersensitive. The present study provides electrophysiological support for previous behavioral studies indicating that the requirement of D1 receptor stimulation for D2 receptor-mediated functional effects (enabling) is not maintained in rats chronically depleted of DA by either 6-OHDA lesions or repeated reserpine.

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“…(8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides.…”

Section: Introductionmentioning

confidence: 99%

“…Circumscribed zones poor in AcChoE staining ("striosomes") are observed against a darker matrix and are coincident with other neurochemical, afferent terminal, and efferent neuron compartments (14). (8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides.…”

mentioning

confidence: 99%

Human striatal dopamine receptors are organized in compartments.

Joyce¹,

Sapp²,

Marshall³

1986

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

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Dopamine (D2) receptors visualized in postmortem human striatum by quantitative autoradiography of [3H]spiroperidol binding are organized into circumscribed zones of low receptor density separated from other such zones by regions of higher D2 density. The D2-rich zones of the caudate nucleus and putamen contain twice the binding of D2-poor zones. The Hill coefficient, obtained from saturation analysis of [3H]spiroperidol binding to thin sections of human striatum, gave a value near unity, indicating the binding was occurring to a single type of site. The patchiness of [3H]spiroperidol binding was unaltered by postincubation removal of lipid from the tissue sections, indicating that a differential absorption of tritium in white and grey matter does not account for the heterogeneous distribution. The D2-rich and D2-poor regions appear to form labyrinths oriented in the anterior-posterior axis and are typically aligned with, respectively, acetylcholinesterase-rich and -poor compartments as visualized on stained adjacent sections. Thus, the distribution of dopamine D2 receptors conforms to the "striosomal" organization of the human caudate-putamen, a finding that suggests that this receptor subtype may mediate the influence of dopamine on distinct neurochemical compartments within the structure. The brain transmitter dopamine has profound effects on mammalian movement and sensorimotor coordination. The massive ascending projections of the ventral midbrain dopaminergic neurons have been well characterized, and strong evidence points to a critical role of this system in several major neurological disorders. Abnormalities of dopaminergic transmission in human brain contribute to Parkinson disease, drug-induced dyskinetic reactions, and the cognitive disturbances of acute psychotic states (1-3). The D2 receptor (4) appears to be the principal site of action of dopamine receptor agonists and antagonists on behavior of humans and animals (5, 6). An understanding of how the D2 receptor contributes to the diversity of dopaminergic influences in the human necessitates that the distribution of these sites be determined with a high degree of anatomical resolution. This has been achieved though the application of the autoradiographic approach for the visualization of dopamine D2 receptors (7) and of computer-assisted quantitative autoradiography (8).In the rodent striatum, a sharp lateral-to-medial gradient of D2 receptors has been observed (8, 9) that appears to correspond to a similar gradient of markers for acetylcholine (AcCho) nerve terminal density (10). (8)(9)(10)(15)(16)(17). Briefly, coronal sections 20 ,um thick were cut at -15°C in a cryostat and thaw-mounted onto gelatin-coated glass slides. Immediately prior to incubation with radioligands, the sections were thawed and dried at room temperature, then transferred to glass dishes containing the preincubation buffer (50 mM Tris HCl, pH 7.1/120 mM NaCl/5 mM KCl/2 mM CaCl2/1 mM MgCl2/1 mM ascorbic acid) for 5 min at 22°C. Then Computer-Assisted Image Analysis...

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Quantitative analysis of [3H]spiroperidol binding to rat forebrain sections: Plasticity of neostriatal dopamine receptors after nigrostriatal injury

Cited by 89 publications

References 22 publications

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Effect of Bilateral 6-Hydroxydopamine Lesions of the Medial Forebrain Bundle on Reaction Time

Lesions of the nigrostriatal dopamine projection increase the inhibitory effects of D1 and D2 dopamine agonists on caudate-putamen neurons and relieve D2 receptors from the necessity of D1 receptor stimulation

Human striatal dopamine receptors are organized in compartments.

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