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1.
The effects of chronic ‘continuous’ infusion and ‘intermittent’ modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [ 3H]mazindol) and D 1 and D 2 DA receptor binding (labelled with [ 3H]SCH 23390 and [ 3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic ‘intermittent’ but not ‘continuous’ levodopa treatments. Following the ‘intermittent’ regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either ‘continuous’ infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [ 3H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [ 3H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [ 3H]sulpiride binding was reduced in both groups of rats receiving levodopa. [ 3H]sulpiride binding in the NAc and OT and [ 3H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. ‘Continuous’ infusion and not ‘intermittent’ injections of levodopa reduced [ 3H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic ‘intermittent’ levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients. 相似文献
2.
The effect of dopamine (DA) on excitatory synaptic transmission was studied in rat neostriatal neurons using intracellular- and whole-cell voltage clamp-recording methods. Depolarizing excitatory postsynaptic potentials (EPSPs) were evoked by cortical stimulation. Superfusion of DA (0.01–10 μM) reversibly decreases EPSP in a concentration-dependent manner and with a estimated IC 5 of 0.3 μM. In addition, the inhibitory effect induced by DA at a low concentratiion (0.1 μM) was antagonized by sulpiride (1–10 nM), a selective D 2 dopaminergic receptor antagonist. However, D 1 dopaminergic receptor antagonist SKF-83566 (1–5 μM) did not affect the blocking effect by DA 0.1 μM. Based on these findings, we conclude that DA at a low concentration ( 0.1 μM) reduced the excitatory response of neostriatal neurons following cortical stimulation via the activation of D 2, but not D 1 dopaminergic receptors, located on the terminals of corticostriatal neurons. 相似文献
3.
Binding of a specific dopamine D 1 receptor antagonist, 125I-SCH 23982, was measured in rat brain sections by quantitative autoradiography at various time intervals, following a knife cut through the striatonigral pathway. Twenty-four hours after lesioning, accumulations of D 1 receptor binding sites were found in sagittal sections both rostral and caudal to the lesion site. No other regions studied (caudate-putamen, nucleus accumbens, olfactory tubercle, and substantia nigra pars reticulata) showed any change in D 1 receptor binding 24h after the lesion. In brain sections obtained 10 days after lesioning, only the substantia nigra pars reticulata had a significant decrease in D 1 receptors ipsilateral to the lesion. These findings suggest the possibility of a presence of bidirectional axonal transport of D 1 receptors in rat striatonigral pathway. 相似文献
4.
[ 3H]SCH 23390 binds stereospecifically and with high affinity to D 1 dopaminergic receptors in the developing chick retina. Autoradiographic experiments revealed that in retinas from 3-day-old chicken and embryos with 12, 14 and 16 days of development, specific labeling of [ 3H]SCH 23390 was mainly observed over the plexiform layers of the tissue, showing that dopaminergic D 1 receptors are localized in retina cell neurites since the initial stages of neurite formation. The total number of [ 3H]SCH 23390 binding sites increased 5-fold during the differentiation of the retina, while the dopamine-dependent cyclic adenosine monophosphate (AMP) accumulation was significantly decreased. Consequently, the ratio between dopamine-dependent cyclic AMP accumulation and [ 3H]SCH 23390 binding sites decreased 10-fold as retina differentiated, indicating that a significant portion of D 1 receptors in retinas from adult chicken are not effectively coupled to adenylate cyclase molecules. 相似文献
5.
1. 1. [3H]Phencyclidine (PCP, Angel Dust) receptors have been characterized using a rat brain binding section technique. 2. 2. [3H]PCP labels a single class of site in rat brain (kd = 46 nM; Bmax = 10.5 fold/slice). Ligand selectivity pattern strongly suggests that [3h]pcp binds to sites relevant for its pharmacological actions. 3. 3. Chronic PCP treatment (10 mg/kg/day for 14 days) decreases the number of sites (Bmax) for [3H]PCP and [3H]spiperone binding but not for [3H]dihydromorphine. These modifications could be related to the development of tolerance and dependence to PCP. 4. 4. Visualization of [3H]PCP binding sites shows high densities of receptors in cortical areas and hyppocampus. Lower densities are observed in caudate-putamen, nucleus accumbens, and amygdala. Negligible quantities of receptors are seen in brain stem and over white matter. 5. 5. The presence of specific [3h]pcp binding sites in rat brain suggests the possible existence of an endogenous ligand for this unique receptor.
Author Keywords: Angel Dust; autoradiography; endogenous ligand; phencyclidine (PCP); receptor binding 相似文献
6.
The in vitro and in vivo effects of (−)-nicotine on dopamine D 2 receptors in the rat neostriatum have been studied using biochemical binding, in situ hybridization and immunocytochemistry. A single i.p. injection (1 mg/kg) of (−)-nicotine resulted in a reduction of the KD value of the D 2 antagonist [ 3H]raclopride binding sites in rat neostriatal membrane preparations at 12 h without any significant change in the Bmax value. This action of (−)-nicotine was counteracted by pretreatment 15 min earlier with the nicotine antagonist mecamylamine (1 mg/kg, i.p.). However, the KD and the Bmax values of the D 2 agonist [ 3H]NPA binding sites in the rat neostriatal membrane preparations were not significantly affected 0.5–48 h after a single i.p. injection with 1 mg/kg of (−)-nicotine. No significant change in neostriatal D 2 receptor mRNA levels was observed at any time interval after the (−)-nicotine injection. No significant change was observed in tyrosine hydroxylase (TH) immunoreactivity in either the substantia nigra or the neostriatum, nor in nigral TH mRNA levels during the time interval studied (4–24 h posttreatment). Furthermore, addition of low (10 nM) or high (1 μM) concentrations of (−)-nicotine in vitro to rat neostriatal membranes did not alter the characteristics of [ 3H]raclopride or [ 3H]NPA binding. These results indicate that a single (−)-nicotine injection can produce a selective and delayed increase in the affinity of D 2 receptors for the antagonist, but not for the agonist without modifying the levels of D 2 receptor mRNA, probably via the activation of central nicotinic receptors. 相似文献
7.
Mice homozygous for the autosomal recesive gene weaver ( wv) exhibit a regionally specific depletion of forebrain dopamine (DA). DA is reduced approximately 70% in the dorsal striatum of homozygotes ( wv/wv) relative to heterozygous (+/ wv) controls while DA content in ventral striatum is relatively unchanged. The goal of the present study was to determine the regional effects of the weaver mutation on striatal DA receptors and DA uptake sites using quantitative autoradiography. Catecholamine histofluorescence was used to examine midbrain DA-containing cell bodies. Compared to behaviorally normal (+/-) littermates, the binding of [ 3H]spiroperidol to D 2 sites was significantly increased in the dorsal but not ventral striatum of wv/wv mice. Binding of the D 1 ligand, [ 3H]SCH23390, was significantly decreased throughout the striatum of wv/wv mice. The binding of [ 3H]mazindol to DA uptake sites was dramatically reduced in all wv/wv striatal regions except the ventrolateral portion. Compared to +/-littermates, wv/wv mice had far fewer fluorescent cell bodies in the substantia nigra and a less pronounced reduction of ventral tegmental area fluorescent somata. These findings support the hypothesis that heterogeneities exist in the genetic control of the mesotelencephalic DA system. The results underscore the usefulness of the weaver mouse in the study of mesostriatal sub-systems, receptor regulation, and potentially as a model of human neuropathologies that affect distinct populations of cells in the mesotelecephalic system. 相似文献
8.
Brain 5-HT 2A receptors exist in two agonist affinity states as a function of their coupling to G q protein. This has not yet been shown in platelets. We examined [ 3H]ketanserin's saturable binding to platelet 5-HT 2A receptors and characteristics of agonist displacement curves of [ 3H]ketanserin binding in healthy control subjects. [ 3H]ketanserin saturation curves showed a trend for a two-site model, reflecting two independent binding sites. At low [ 3H]ketanserin concentrations, agonist displacement curves were flat and best fit a two-site model, indicating the existence of two agonist affinity states. Guanylyl 5′-imidotriphosphate [Gpp(NH)p] induced a significant rightward shift in agonist displacement curves to fit a one-site model. Platelet membrane 5-HT 2A receptors exist in two agonist affinity states that are regulated by G q protein. Platelet 5-HT 2A receptors provide an accessible model for examining possible dysregulation in the agonist affinity or coupling efficiency to the phosphoinositide system in psychiatric disorders and their modulation by psychotropic medications. 相似文献
9.
We examined binding of the GABA B receptor agonist baclofen to brain synaptic membranes as a function of the natural variations in gonadal steroids that occur during the estrous cycle of the adult rat. We found that the binding of baclofen to neocortical membranes varied systematically as a function of the estrous cycle, with the lowest binding occuring during the estrus stage. Binding to archicortical (hippocampal) and hypothalamic preparations also varied with the estrous cycle, except that the lowest level of binding in these latter cases occurred during the diestrus stage. The variation of [ 3H]baclofen binding during the estrous cycle was different with respect to the binding of [ 3H]muscimol, an agonist for GABA A receptors, and [ 3H]8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist for serotonin 5-HT 1A receptors that shares similar G proteins and effectors with GABA B receptors. Saturation binding studies of cortical GABA B receptors showed that apparent receptor density ( Bmax) rather than affinity ( Kd)best accountd for the change in binding during the estrous cycle in that Bmax), like total specific binding, was at a minimum during the estrus stage. The robust regulation of GABA B receptors in neocortex was unexpected and its functional significance is at present unknown. However, the correlation of the menstrual cycle with mood and other behavioral changes, and the correlations of the estrous and menstrual cycles with seizure susceptibility, may somehow depend upon hormonal regulation of transmitter systems such as the one we have observed here. 相似文献
10.
Using [ 3H]sumatriptan as a radioligand, 5-hydroxytryptamine (5-HT) 1B receptors were examined in posterior striatum and midbrain post-mortem tissue sections of 12 patients who had died from representative degenerative movement disorders as compared to nine controls. In the control human basal ganglia, the highest densities of [ 3H]sumatriptan binding were observed in the globus pallidus and substantia nigra. No significant change in the density of [ 3H]sumatriptan binding sites was found in the striatum and substantia nigra of the six Parkinson's disease brains. In the two brains from patients with progressive supranuclear palsy an increase was found in the densities of [ 3H]sumatriptan binding sites, most marked in the substantia nigra. In contrast, [ 3H]sumatriptan labelling was almost absent in the striatonigral degeneration brain and was markedly reduced in the three Huntington's disease brains. This study indicates that the status of 5-HT 1B receptors is different in each degenerative movement disorder and suggests that human 5-HT 1B receptors are located somatodendritically on GABAergic and peptidergic caudate-putamen neurons which project to the substantia nigra and globus pallidus, where these receptors are presynaptic. 相似文献
11.
To examine the possible involvement of D 1 dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D 1 receptors labeled with [ 3H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in Kd in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither Kd nor Bmax changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [ 3H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D 1 receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization. 相似文献
12.
The autoradiographic distribution and density of muscarinic receptors was studied in the neostriatum of rats with long-term unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway and in lesioned rats who had additionally received embryonic substantia nigra grafts in the dopamine denervated striatum. Muscarinic receptors were labeled with [ 3H]quinuclidinyl benzilate (QNB), M 1 receptors were directly labeled with [ 3H]pirenzepine (PZ) and non-M 1 receptors were labeled by the competition of 100 nM PZ with [ 3H]QNB. The density and distribution of muscarinic receptors were directly compared to the sodium-dependent, high-affinity, choline uptake sites as labeled with [ 3H]hemicholinium-3 (HC-3). In the 6-OHDA-lesioned animals, there was a 25% reduction in muscarinic receptors labeled with [ 3H]QNB. Subtype analysis showed that there was a reduction of both M 1 (−26%) and non-M 1 (−33%) receptors. A normal density of both muscarinic receptor populations was found in animals with successful transplants. Saturation analysis demonstrated that the changes, in muscarinic receptor density, were due to a change in receptor number ( Bmax) and not affinity ( Kd). There was no significant change in [ 3H]HC-3 binding in the 6-OHDA-lesioned or transplanted animals, indicating that alterations in muscarinic receptors were not due to transynaptic degeneration of striatal cholinergic interneurons. The findings of downregulation of muscarinic receptors following long-term dopamine denervation and the subsequent normalization of muscarinic receptor density after fetal mesencephalic transplantation suggests that transplanted substantia nigra cells are able to restore inhibitory control on striatal cholinergic interneurons. 相似文献
13.
The aim was to test the dopamine hypothesis of schizophrenia in a further analysis of D 2-like dopamine binding using the radioligand [ 11C]raclopride and high resolution 3-dimensional (3D) PET. Eighteen drug-naive patients with schizophrenia and seventeen control subjects were examined. The D 2 binding potential (BP) in the putamen, the caudate and the thalamus was calculated using the simplified reference tissue model. The volume of regions of interest was controlled for by MRI. Symptoms were rated with the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). No significant group differences were found for D 2 BP in the putamen or in the caudate and there was no significant hemispheric difference for any region. In the right thalamus the D 2 BP was significantly lower in patients as compared to control subjects, whereas a numerical difference did not reach statistical significance for the left thalamus. There was no significant correlation between D 2 BP and total PANSS score in any region. There was a highly significant age effect in the caudate and in the putamen, but not in the thalamus. In this relatively large PET study of exclusively drug-naive schizophrenic patients, a lower D 2 BP in the right thalamus was found in the patient group. This finding is in agreement with two previous studies in Sweden and in Japan using the high-affinity radioligand [ 11C]FLB 457 and provide further support for a role of dopamine in the thalamus related to the pathophysiology of schizophrenia. 相似文献
14.
In rats, the non-opioid β-endorphin (βE) fragment desenkephalin-γ-endorphin (DEγE, βE 6–17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DEγE might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DEγE was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [ 3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [ 3H]DA. The selective D 2 receptor antagonist (−)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D 2 type. DEγE was tested at several concentrations (10 −9–10 −6) and under various experimental conditions. DEγE, by itself, did not affect either the electrically stimulated or the basal release of [ 3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DEγE, but this effect was present in some experiments only. It is concluded that DEγE does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DEγE does not occur at the level of this receptor. 相似文献
15.
From a Wistar population two rat lines were generated using as criterion the behavioral response to the dopamine agonist apomorphine. Rats of the apomorphine-susceptible (apo-sus) line revealed a vigorous gnawing response to apomorphine administration while the other rat line, the apomorphine-unsusceptible (apo-unsus) line, was selected for lack of response to the drug. In the present study using the 12th and 13th generation of these genetically selected lines, we have investigated whether this difference in apomorphine responsiveness was correlated with changes in dopamine neurochemistry. Therefore, we measured tyrosine hydroxylase (TH), the rate limiting enzyme in dopamine synthesis, as well as dopamine D 1 and D 2 receptor mRNA levels in discrete brain regions by in situ hybridization. Dopamine ( D2/D3) receptor binding was assessed with [ 125I]iodosulpride in a membrane binding assay and by quantitative autoradiography on tissue sections. [ 3H]SCH 23390 was used to analyze D 1 receptor binding. Apo-sus rats displayed significantly higher TH mRNA levels in the A 9 cell group of the substantia nigra pars compacta and in the A 12 cell group of the arcuate nucleus. No difference was found in the A 10 cell group of the VTA and the A 6 cell group of the locus coeruleus. The density of D2/3 binding sites as well as D 1 receptor mRNA levels in the striatal projection area of the A 9 substantia nigra neurons, were significantly elevated in apo-sus rats. Dopamine D 2 receptor mRNA and D 1 receptor binding levels in caudate putamen and nucleus accumbens, however, were similar in rats of both lines. In conclusion, high apomorphine susceptibility is related to a potentially enhanced dopamine responsiveness selective for the nigrostriatal and tuberoinfundibular pathways. 相似文献
16.
We examined whether administration of Δ9-tetrahydrocannabinol (THC) induces the expression of Fos protein or not in the rat brain. A single administration of 3.2 and 10 mg/kg THC produced a dose-dependent and significant increase in Fos-immunoreactive cells in the striatum, particularly in its dorsomedial portions. The peak increase was reached 2 h after THC treatment and was absent at 8 h. Fos induction was also observed in the nucleus accumbens after administration of 10 mg/kg THC. However, in the globus pallidus, hippocampus and substantia nigra pars reticula, abundant in cannabinoid receptors, there were few or no Fos-immunoreactive cells induced by 10 mg/kg THC. SCH-23390, a selective dopamine D 1 receptor antagonist, at 0.32 mg/kg produced a significant block of the effects of THC on Fos expression in the striatum and the nucleus accumbens. Administration of 100 mg/kg (-)-sulpiride, a selective dopamine D 2 receptor antagonist, failed to block the effect of THC on Fos expression in both the striatum and the nucleus accumbens. These findings indicate that THC induces the expression of Fos protein and that this expression is mediated at least by dopamine D 1 receptors. 相似文献
17.
The recent development of in vitro autoradiography techniques has enabled investigators to determine the distribution and relative levels of multiple ligand binding sites in discrete anatomical areas. In this study we used semi-quantitative in vitro autoradiography to compare the levels of binding to central mu 1, mu 2, and delta opioids sites in two strains of mice, C57BL/6BY and CXBK. The CXBK strain is known to be deficient in whole brain opioid binding sites and to be less sensitive than the C57 strain to the analgesic and locomotor stimulatory effects of opiates and opioids. Delta sites were visualized using [ 3H][d-Ala 2-d-Leu 5]-enkephalin (DADL) plus a low concentration of morphine, total mu sites (mu 1 and mu 2) were visualized using [ 3H]dihydromorphine (DHM), and mu 2 sites were visualized using [ 3H]DHM plus a low concentration of DADL. Binding to mu 1 sites was determined by subtracting mu 2 binding from total mu binding. We found that the two strains did not consistently differ in the levels of delta sites; in some areas the CXBKs had lower levels but in many areas they had levels equal to or greater than those for the C57s. The CXBK strain, however, either had less or the same amount of mu binding as the C57 strain in all areas studied. The CXBK strain was especially deficient in mu 1 binding, particularly in areas involved in pain processing. 相似文献
18.
Positron emission tomography (PET) was used to assess the role of dopamine D 2 receptors in the striatum and serotonin S 2 receptors in the frontal cortex in the susceptibility to methamphetamine-induced psychosis. Subjects were six men who had previously experienced methamphetamine psychosis (methamphetamine subjects) and 10 age- and sex-matched control subjects. The radiotracer used was 11C- N-methylspiperone. Although binding availability, assessed by dynamic analysis, in the two regions did not differ between the two groups, the ratio of binding availability in the striatum to that in the frontal cortex significantly decreased in the methamphetamine subjects as compared with the control subjects. These findings suggest that an imbalance in the activity of these two receptors may be related to the susceptibility to methamphetamine psychosis. 相似文献
19.
Opioid receptors can be labeled with [ 3H]ligands in lightly fixed tissue sections mounted on microscope slides. The preparation of these sections does not seem to alter any of the known characteristics of opioid receptors. The light microscopic autoradiographic distribution of these binding sites can be observed if one attaches emulsion-coated coverslips to these slides to obtain autoradiograms. The distribution of [ 3H]diprenorphine binding sites determined by this in vitro method is identical to the distribution found in earlier studies utilizing in vivo labeling of opioid receptors. In addition, [ 3H]opioid peptide binding sites and [ 3H]dihydromorphine binding sites may be similar, perhaps identical, to those for [ 3H]diprenorphine, an opiate antagonist. This method has several important advantages over earlier methods for determining the autoradiographic localization of receptors. It is possible, by washing, to reduce nonspecific binding to low levels. Since receptor labeling is performed with single tissue sections mounted on slides, one can examine different receptors in different but adjacent sections. One can use ligands that are not entirely suitable for in vivo labeling (For example, one can use [3H]peptides which do not normally cross the blood-brain barrier). One can perform autoradiographic studies after laveling tissues under a wide variety of conditions (For example, one can examine the effects of various ions and nucleotides on ligand binding distributions). This technique seems to be free of various artifacts, such as edge artifacts, which were common by techniques used in our laboratory earlier. Since one does not have to load an entire animal with radioactive ligand as one must with in vivo labeling, this approach is economically advantageous. One can use postmortem tissue, including that from humans to study receptor distribution with a high anatomical resolution. 相似文献
20.
Unilateral 6-hydroxydopamine (6-OHDA) lesions of substantia nigra pars compacta (SNPC) neurons in rats induce behavioural hypersensitivity to dopaminergic agonists. However, the role of specific dopamine receptors is unclear, and potential alterations in their transduction mechanisms remain to be evaluated. The present study addressed these issues employing the dopaminergic agonist, quinelorane, which efficaciously stimulated G-protein activation (as assessed by [ 35S]GTPγS binding) at cloned hD 2 (and hD 3) receptors. At rat striatal membranes, dopamine stimulated [ 35S]GTPγS binding by 1.9-fold over basal, but its actions were only partially reversed by the selective D 2/D 3 receptor antagonist, raclopride, indicating the involvement of other receptor subtypes. In contrast, quinelorane-induced stimulation (48% of the effect of dopamine) was abolished by raclopride, and by the D 2 receptor antagonist, L741,626. Further, novel antagonists selective for D 3 and D 4 receptors, S33084 and S18126, respectively, blocked the actions of quinelorane at concentrations corresponding to their affinities for D 2 receptors. Quinelorane potently induced contralateral rotation in unilaterally 6-OHDA-lesioned rats, an effect abolished by raclopride and L741,626, but not by D 3 and D 4 receptor-selective doses of S33084 and S18126, respectively. In functional ([ 35S]GTPγS) autoradiography experiments, quinelorane stimulated G-protein activation in caudate putamen and, to a lesser extent, in nucleus accumbens and cingulate cortex of naive rats. In unilaterally SNPC-lesioned rats, quinelorane-induced G-protein activation in the caudate putamen on the non-lesioned side was similar to that seen in naive animals (50% stimulation), but significantly greater on the lesioned side (80%). This increase was both pharmacologically and regionally specific since it was reversed by raclopride, and was not observed in nucleus accumbens or cingulate cortex. In conclusion, the present data indicate that, in rat striatum, the actions of quinelorane are mediated primarily by D 2 receptors, and suggest that behavioural hypersensitivity to this agonist, induced by unilateral SNPC lesions, is associated with an increase in D 2, but not D 3 or D 4, receptor-mediated G-protein activation. 相似文献
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