bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alterations in dopamine uptake sites and D1 and D2 receptors in cats symptomatic for and recovered from experimental parkinsonism
Authors: Frohna Paul A. , Rothblat David S. , Joyce Jeffrey N. , Schneider Jay S. 
Published: December 2004

AbstractThe administration of the neurotoxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) to adult cats severely disrupts the dopaminergic innervation of the striatum. Animals display a parkinson‐like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidity, which spontaneously recovers by 4–6 weeks after the last administration of MPTP. In this study we used quantitative receptor autoradiography to examine changes in DA uptake sites and DA receptors in the basal ganglia of normal, and symptomatic and recovered MPTP‐treated cats.Consistent with the destruction of the nigrostriatal DA pathway, there was a severe loss of DA uptake sites, labeled with [3H]‐mazindol, in the caudate nucleus (64–82%), nucleus accumbens (44%), putamen (63%), and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. Following behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [3H]‐SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (>24%; P < 0.05) of symptomatic cats and in all regions of the caudate‐putamen (>30%; P < 0.05) of recovered animals. [3H]‐SCH 23390 binding in tree substantia nigra pars reticulata was half of that in the striatum and showed no changes in symptomatic or recovered animals. No alterations in the binding of [1251]‐epidepride to D2 receptors was observed in any region of the striatum in either, symptomatic or recovered animals. [1251]‐Epidepride binding in the SNc was decreased by >36% (P < 0.05) following MPTP treatment.These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptake sites throughout the striatum and that recovery of sensorimotor function in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem to be correlated with a general elevation of Dl receptors throughout the striatal complex. The present data also show that direct correlations between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are difficult and that the relationships between DA receptors/transporters and behavior require further study. © 1995 Wiley‐Liss, Inc.
Amphetamine‐Induced time‐dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: A microdialysis study in behaving rats
Authors: Paulson Pamela E. , Robinson Terry E. 
Published: December 2004

AbstractThe purpose of this study was to compare the effects of amphetamine exposure on subsequent amphetamine‐induced changes in behavior and dopamine (DA) release in the dorsal and ventral striatum, as a function of time following the discontinuation of repeated amphetamine treatment. Rats were pretreated with either saline or an escalating‐dose amphetamine regimen, and then received a 0.5 mg/kg amphetamine “challenge” after either 3, 7, or 28 days of withdrawal. Animals tested after 28 days of withdrawal were hypersensitive (sensitized) to the locomotor‐activating effects of amphetamine, and relative to control animals showed a significant enhancement in amphetamine‐stimulated DA release in both the dorsal and ventral striatum, as revealed by in vivo microdialysis. Animals tested after only 3 or 7 days of withdrawal showed neither behavioral sensitization nor enhanced amphetamine‐stimulated DA release. These results establish that time‐dependent changes in behavioral sensitization to amphetamine are associated with time‐dependent changes in amphetamine‐stimulated DA release, and support the hypothesis that persistent sensitization‐related changes in striatal DA neurotransmission contribute to the expression of behavioral sensitization. © 1995 Wiley‐Liss, Inc.
Evidence against differential release of noradrenaline, neuropeptide Y, and dopamine‐β‐hydroxylase from adrenergic nerves in the isolated perfused sheep spleen
Authors: De Potter W. P. , Kurzawa R. , Miserez B. , Coen E. P. 
Published: December 2004

AbstractThe subcellular storage and release of noradrenaline (NA), dopamine‐β‐hydroxylase (DβH), and neuropeptide Y (NPY) was studied in the isolated perfused sheep spleen. Subcellular distribution studies showed a bimodal distribution for NA which was well reflected by DβH and indicated the occurrence of two types of NA storage vesicles. The most dense, presumably large dense‐cored vesicles (LDV), contain both membrane‐bound and soluble DβH the less dense presumably corresponds to small dense‐cored vesicles (SDV) and at least does not contain soluble DβH. The distribution of NPY is extended but shows a peak only at the position of LDV, indicating that LDV contain NPY. Continuous electrical stimulation of the splenic nerve at 2 Hz, 5 Hz, 10 Hz, and 20 Hz or at 20 hz with bursts induced the release of NA, NPY, and DβH. The ratio among these components was constant. The fractional release of DβH and NA was comparable at all frequencies used; that of NPY was 10–20 times lower, suggesting the occurrence of a large nonreleasable NPY pool. The present data argue against a high frequency stimulation or intermittent stimulation‐induced preferential release of NPY from adrenergic neurons and question the concept of frequency‐dependent chemical coding of sympathetic transmission in general. The simplest interpretation of our data is that NA and NPY are released at all frequencies from a single pool. The present findings might signify that only large dense‐cored vesicles are involved in the sympathetic stimulation‐evoked secretion of catecholamines from adrenergic nerve terminals of the isolated sheep spleen. © 1995 Wiley‐Liss, Inc.
Modulation of GABAAreceptor binding in human brain by neuroactive steroids: Species and brain regional differences
Authors: Nguyen Quyen , Sapp Douglas W. , Van Ness Paul C. , Olsen Richard W. 
Published: December 2004

AbstractAllosteric modulation by neuroactive steroids of radioligand binding sites on the GABAAreceptor complex was demonstrated by autoradiography in vitro in several regions of human brain and the effects compared to those in rat brain. Comparing human and rat, two steroids known to be active in enhancing GABA‐mediated postsynaptic inhibition, 5α‐pregnane‐3α21‐diol‐20‐one (tetrahydro‐deoxycorticosterone, THDOC) and alphaxalone (5α‐pregnane‐3α‐hdyroxy‐11,20‐dione), allosterically inhibited [35S]TBPS binding to the picrotoxin/convulsant site in both species in several regions including the hippocampus. Unlike rat, human brain binding of [3]Hlflunitrazepam to the benzodiazepine site was not enhanced by alphaxalone (at any concentration), but was unaffected in many regions and inhibited in others. Binding of [3H]muscimol to high and low affinity GABA sites were enhanced by both steroids in all tested regions of rat brain, although to varying degrees. However, several lobes of human cortex showed no modulation of muscimol binding by either steroid, and THDOC, but not alphaxolone, inhibited in some areas. Comparing regions, THDOC at high concentrations (10 μM) enhanced in human frontal lobe and primary sensory and motor cortex, with greater effect in deep layers than superficial. This steroid had no effect in other parts of parietal lobe and inhibited muscimol binding in temporal lobe, primary visual cortex, and other parts of occipital lobe. Concentration‐dependence curves for THDOC showed regional variation, e.g., in the hippocampal formation and surrounding neocortex. These regional and species differences are consistent with the existence of multiple GABAAreceptor subtypes that differ in pharmacology. This heterogeneity provides both the opportunity and the difficulty of targeting clinically useful medications such as antiepileptic drugs to the appropriate human brain regions, and the species differences in regional subtype expression suggest caution in use of animal models. © 1995 Wiley‐Liss, Inc.
Effect of injury on the bi‐affinity α1‐adrenoreceptor binding in rat brain in vivo
Authors: Dyve Suzan , Yang Yu‐Jia , McHugh Michael , Gjedde Albert , Pappius Hanna M. 
Published: December 2004

AbstractFocal freezing lesions in rats cause a widespread decrease of cortical glucose utilization in the lesioned hemisphere, probably as a reflection of depressed cortical activity. The noradrenergic neurotransmitter system was implicated in these alterations when it was demonstrated that prazosin, a specific norepinephrine (NE) antagonist at β1‐adrenergic receptors, prevented their development. In normal rat brain, specific binding of [125I]HEAT [(±)2‐(3‐[125I]iodo‐4‐hydroxyphenyl)‐ethyl‐aminomethyltetralone], another selective α1‐adrenoreceptor ligand, was demonstrated in vivo at sites consistent with the α1A‐ and α1B‐adrenoreceptor subtypes. In the present study, the effect of a freezing lesion on specific binding of [125I]HEAT in rat brain in vivo was determined three days after traumatization when cortical glucose use suggested the greatest degree of functional depression. The steady‐state volumes of distribution of [125I]HEAT three days after injury were significantly increased in all the cortical areas of the lesioned hemisphere, but not in the subcortical structures. Injury did not modify the binding affinities for HEAT. However, a statistically significant increase in the number of low‐affinity binding sites for this ligand was demonstrated in all cortical areas of the lesioned hemisphere, but not in subcortical structures. The traumatization did not modify Bmax. estimates for the high‐affinity binding of HEAT. The results support the hypothesis that changes in the noradrenergic system are of functional importance in brain injury and that at least some effects of injury are mediated by α1B‐adrenergic receptors. © 1995 Wiley‐Liss, Inc.
Protective effects of MK‐801 on methamphetamine‐induced depletion of dopaminergic and serotonergic terminals and striatal astrocytic response: An immunohistochemical study
Authors: Pu Cunfeng , Vorhees Charles V. 
Published: December 2004

AbstractIt has been shown previously that methamphetamine induces dopaminergic nerve terminal degeneration, serotonin depletion and striatal reactive astrogliosis, and that the noncompetitive N‐methyl‐D‐aspartate (NMDA) antagonist MK‐801 can block methamphetamine (MA)‐induced depletion of dopamine and serotonin and reduction in activity of their synthetic enzymes. In this study, immunohistochemistry was used to evaluate the effect of MK‐801 on methamphetamine‐induced neuropathological alterations of dopaminergic and serotonergic terminals and striatal astrocytic responses. Adult male rats were treated with methamphetamine (4 injections of 10 mg/kg at 2 hour intervals) in conjunction with MK‐801 which was administered 15 min before each methamphetamine administration at doses of 1 mg/kg or 2 mg/kg. Brains were examined three days following treatment. MK‐801 administration prevented methamphetamine‐induced depletion of 5‐hydroxytryptophan (5‐HT) terminals in the forebrain and depletion of tyrosine hydroxylase‐positive dopaminergic terminals and astrocytic response in the neostriatum in most animals. These results support the concept that excitatory amino acids acting through an NMDA receptor are involved in methamphetamine‐induced neuronal damage on dopaminergic and serotonergic terminal fields. A minor depletion of TH‐positive terminals and astrogliosis in the neostriatum was seen in three of nine MA‐MK‐801‐treated animals. This indicates that the protective effects of MK‐801 on MA‐induced dopaminergic terminal degeneration varies among animals with complete protection in most animals and partial protection in the others using the present doses and dosing regimen. © 1995 Wiley‐Liss, Inc.
6β‐[125Iodo]‐3, 14‐dihydroxy‐17‐methyl‐4, 5α‐epoxymorphinan ([125I]IOXY‐AGO): A potent and selective radioligand for opioid μ receptors
Authors: Xu Heng , Goodman Carl B. , Partilla John S. , Ni Qi , Kayakiri Hiroshi , Rice Kenner C. , Rothman Richard B. 
Published: December 2004

AbstractThe recent cloning and expression of an opioid μ receptor has opened up new opportunities for research in opioid pharmacology. The relatively low level of transient receptor expression in COS cells emphasizes the need for radioligands with high specific activity and low nonspecific binding with which to label receptors. In addition, recent data indicating that agonists and antagonists bind to different domains on the same receptor protein indicate the utility of having both agonist and antagonist radioligands available for the study of opioid receptor mechanisms. Previous studies characterized the binding of the. opioid antagonist 6β‐[125iodo]‐3,14‐dihydroxy‐17‐cyclopropylmethyl‐4,5α‐epoxymorphinan ([125I]IOXY) and showed that this naltrexone analog labels μ and K2 receptors in rat and guinea pig brain with high affinity and low nonspecific binding. In the present study, we synthesized the agonist congener of IOXY, 6β‐iodo‐3,14‐dihydroxy‐17‐methyl‐4,5α‐epoxymorphinan. We named this novel agent IOXY‐AGO for IOXY‐agonist. Competition binding studies showed that IOXY‐AGO has high affinity for δ receptors (Ki = 0.28 nM) and lower affinity for δ (Ki = 18.7 nM) and K1 (Ki = 33.9 nM), K2a (Ki = 38.4 nM) and K2b (Ki = 58.2 nM) binding sites. IOXY‐AGO was radioiodinated to a specific activity of 2,200 Ci/mmol. [125I]IOXY‐AGO binding was rapid, readily reversible, and characterized by low nonspecific binding. Equilibrium binding studies showed that it labeled a single class of binding sites (Kd = 1.46 nM, Bmax = 112 fmol/mg protein) with the characteristics of an opioid μ receptor. Receptor autoradiography experiments showed that [125I]IOXY‐AGO labeled binding sites with the anatomical distribution of μ receptors. Viewed collectively, these studies suggest that [125I]IOXY‐AGO will be a useful radioligand for characterizing opioid μ receptors. © 1995 Wiley‐Liss, Inc.
Anatomical localization of SKF‐38393‐induced behaviors in rats using the irreversible monoamine receptor antagonist EEDQ
Authors: Neisewander Janet L. , Ong Alvin , McGonigle Paul 
Published: December 2004

AbstractThis study was designed to localize the population of dopamine D1‐like receptors involved in grooming and oral movements elicited by systemic administration of the Dl‐selective agonist SKF‐38393. Receptors in specific dopamine terminal regions were inactivated by intracranial injection of the nonselective irreversible antagonist N‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ). The effect of these injections on behaviors induced by systemic administration of SKF‐38393 (10 mg/kg) was measured 48 hours later. The specific populations of D1‐like receptors inactivated by the EEDQ injections were identified as a loss of 3H‐SCH‐23390 binding in a given region using quantitative autoradiography. EEDQ (1.5 μg/μl/side) injected into the nucleus accumbens (NAc) did not alter SKF‐38393‐induced behaviors. Similarly, injection of EEDQ into the medial caudate‐putamen (CPu) failed to alter these behaviors. In contrast, EEDQ (0.15‐1.5 μg/μl/side) injected into the lateral CPu decreased both SKF‐38393‐induced grooming and oral movements, with complete blockade of grooming observed at the highest dose. To determine whether this effect of EEDQ was due to inactivation of Dl‐like receptors, separate groups of animals were pretreated with SCH‐23390 (3 mg/kg, S.C.) 15 min prior to injection with EEDQ. Pretreatment with SCH‐23390 prevented the disruption of SKF‐38393‐induced behaviors, as well as the loss of 3H‐SCH‐23390‐labeled binding sites observed after injection of EEDQ into the lateral CPu. EEDQ injections that produced disruption of SKF‐38393‐induced behaviors were associated with a greater loss of binding in the lateral CPu relative to other regions examined including the NAc, medial CPu, and globus pallidus. Furthermore, EEDQ injections that produced the greatest loss of 3H‐SCH‐23390 binding in the latter three regions did not disrupt SKF‐38393 induced behavior. These results demonstrate that stimulation of Dl‐like receptors in the lateral CPu is necessary for behaviors induced by systemic administration of SKF‐38393. The results also demonstrate the utility of this “receptor lesion” technique to localize receptor‐mediated behaviors. © 1995 Wiley‐Liss, Inc.
Evidence for 5‐HT autoreceptor‐mediated, nerve impulse‐independent, control of 5‐HT synthesis in the rat brain
Authors: Hjorth Stephan , Suchowski Camille S. , Galloway Matthew P. 
Published: December 2004

AbstractTo gain further insight into the operation of 5‐HT autoreceptor‐mediated feedback control of 5‐HT biosynthesis in serotonergic nerve terminal areas, the effect of the 5‐HT1B and the 5‐HT1A receptor agonists, TFMPP and 8‐OH‐DPAT, respectively, were investigated in the rat central nervous system (CNS) using in vivo and in vitro neurochemical approaches. TFMPP suppressed 5‐HT synthesis (5‐HTP accumulation after decarboxylase inhibition) both in vivo and in vitro. In vivo, the 5‐HT synthesissuppressing effect of the drug (3.0 mg/kg, s.c.) proved resistant to either acute hemitransection or reserpine (5 mg/kg, i.p.; 90 min before) pretreatment. In vitro, in cortical, hippocampal and striatal slice preparations, TFMPP (0.1–10 μM) decreased 5‐HT synthesis under basal and stimulated (30 mM K+) conditions, an effect which was unaltered by prior in vivo reserpine‐induced 5‐HT depletion but was attenuated in the presence of 5‐HT1B receptor antagonists such as methiothepin, cyanopindolol or propranolol. The 8‐OH‐DPAT (0.1 mg/kg, s.c.)‐induced decrease of 5‐HT synthesis in vivo was abolished by hemitransection but resistant to acute reserpine pretreatment; 8‐OH‐DPAT (10 μM) did not decrease 5‐HT synthesis in vitro. In conclusion, the present study confirms the importance of 5‐HT autoreceptors in the feedback control of nerve terminal 5‐HT biosynthesis. Specifically, our data indicate: (1) that the reduction of rat brain 5‐HT synthesis after TFMPP is mediated by 5‐HT1B autoreceptors located on the serotonergic axon terminals, and (2) that the effect is directly mediated and occurs independently of 5‐HT neuronal firing and intact monoamine stores. © 1995 Wiley‐Liss, Inc.
Functional diversity of GABAA receptor ligand‐gated chloride channels in rat synaptoneurosomes
Authors: Ito Yoshihisa , Segawa Katsuya , Fukuda Hideomi 
Published: December 2004

AbstractExperiments were performed to examine neurochemically the functional diversity of GABAA receptors as measured by muscimol‐, 5α‐pregnane‐3α,21‐diol‐20‐one (THDOC)‐, and pentobarbital‐stimulated 36C1− uptake, and region‐specific changes in muscimol THDOC‐ and THDOC‐induced potentiation of muscimol‐stimulated 36CI– uptake in rats treated acutely or subacutely with a subconvulsive dose of bicuculline. The data, for stimulation of 36C1– uptake by muscimol showed a single binding site interaction in the cerebral cortex, hippocampus and cerebellum. The concentration‐response curves for muscimol in the cerebral cortex and hippocampus were steep and indicated an increase of, approximately 130% at the maximum concentration. In contrast, the curve for the cerebellum was shallow and, exhibited a smaller maximal response (∽60%). Apparent affinity for muscimol also differed among these brain regions. The regional differences in 36CI– uptake induced by THDOC and pentobarbital were not as apparent as those induced by muscimol; however, the maximal modulatory effect of pentobarbital, in the hippocampus was significantly higher than that in the cerebellum. In rats treated subacutely with a subconvulsive dose of bicuculline, a significant increase in muscimol‐stimulated 36C1‐ uptake was observed in the cerebellum but not in the frontal cortex or hippocampus. Analysis of the concentration‐response curves for muscimol‐stimulated 36CI− uptake in the cerebellum revealed that the Vmax for muscimol in the subacutely treated group was significantly higher than those for muscimol in the control and acutely treated groups without any differences in the KD value. In addition, THDOC‐induced potentiation of muscimol‐stimulated 36CI− uptake in the subacutely treated group was significantly higher than those in the control and acutely treated groups when a lower concentration (10 nM) of THDOC was used. These results suggest that regional variation of 36C1− uptake stimulated by muscimol is more apparent than those stimulated by THDOC and pentobarbital. The present results, along with our previous findings, also indicate that region‐specific bicuculline up‐regulation of GABAA receptors in the cerebellum involves changes not only in binding characteristics but also in function of GABA receptor‐gated chloride channel. © 1995 Wiley‐Liss, Inc.
Lack of effect of chronic morphine treatment and naloxone‐precipitated withdrawal on tyrosine hydroxylase, galanin, and neuropeptide Y mRNA levels in the rat locus coeruleus
Authors: Holmes Philip V. , de Bartolomeis Andrea , Koprivica Vuk , Crawley Jacqueline N. 
Published: December 2004

AbstractMorphine dependence was experimentally induced in rats by daily injection of increasing doses of morphine for seven days. Withdrawal was precipitated in half of the morphine‐dependent rats by a single injection of naloxone on day 8. Behavioral signs of withdrawal weret evident in the morphine/naloxone group. Gene expression in locus coeruleus (LC) neurons was investigated using quantitative in situ hybridization analysis. Messenger RNA (mRNA) levels for tyrosine hydroxylase (TH), the rate‐limiting enzyme in catecholamine synthesis, and for precursors to galanin (GAL) and neuropep tide Y (NPY), peptides that coexist with norepinephrine in LC neurons, were not altered by chronic morphine treatment or naloxone‐precipitated withdrawal. In contrast, mRNA levels for c fos were dramatically elevated in the LC following naloxone‐precipitated withdrawal. Chronic morphine treatment caused a small decrease in levels of mRNA encoding the precursor to corticotropin‐releasing factor (CRF) in Barrington's nucleus. Although long‐term adaptations of LC neurons have previously been implicated in the development of morphine tolerance, dependence, and withdrawal, alterations in the levels of TH, GAL, or NPY mRNA in the LC apparently do not underlie this process. © 1995 Wiley‐Liss, Inc.
Lipophilic metabolite of [123I]β‐CIT in human plasma may obstruct quantitation of the dopamine transporter
Authors: Bergström Kim A. , Halldin Christer , Kuikka Jyrki T. , Swahn Carl‐Gunnar , Tiihonen Jari , Hiltunen Jukka , Länsimies Esko , Farde Lars 
Published: December 2004

AbstractI‐123 or C‐11 labelled 2β‐carbomethoxy‐3β‐(4‐iodophenyl)tropane (β‐CIT) is a recently developed radioligand for the study of dopamine and serotonin reuptake sites in humans with single photon emission tomography (SPET) or positron emission tomography (PET). Determination of the radioligand metabolite pattern is fundamental for a quantitative analysis of radioligand binding. The metabolism of [123I]β‐CIT was determined by a gradient HPLC method in plasma samples of six human subjects. Two metabolites of [123I]β‐CIT were found, a polar and a lipophilic. At 4 h after [123I]β‐CIT injection the percentages of parent compound and polar and lipophilic metabolites were 23 ± 3% (mean ± SD), 33 ± 11%, and 44 ± 8%, respectively. The lipophilic metabolite might pass the blood‐brain barrier and account for a fraction of free and nonspecifically bound radioactivity in brain. The existence of a lipophilic metabolite of [123I]β‐CIT may obstruct the use of simple ratio methods for quantitation of the dopamine transporter in brain. © 1995 Wiley‐Liss, Inc.