bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrophysiological profile of the new atypical neuroleptic, sertindole, on midbrain dopamine neurones in rats: Acute and repeated treatment
Authors: Skarsfeldt Torben 
Published: December 2004

AbstractSertindole (Lundbeck code No. Lu 23‐174) (1‐[2‐[4‐[5‐chloro‐1‐(4‐fluorophenyl)‐1H‐indol‐3‐yl]‐1‐piperidinyl]ethyl]‐2‐ imidazolidinone) is a new potential neuroleptic compound.After 3 weeks of treatment sertindole shows an extreme selectivity to inhibit the number of spontaneously active dopaminergic (DA) neurones in ventral tegmental area (VTA) while leaving the number of active DA neurones in substantia nigra pars compacta (SNC) unaffected. Acute injection of apomorphine or baclofen reverse the inhibition of activity seen after repeated treatment with sertindole. This suggests that sertindole induces a depolarization inactivation of the DA neurones. The depolarization inactivation is reversible since normal activity of DA neurones is found in both SNC and VTA after two weeks withdrawal from repeated treatment with a low dose with sertindole. One or two weeks administration of a high dose of sertindole induced only minor effects on the DA neurones in VTA; i.e., in order to obtain the depolarization inactivation sertindole requires 3 weeks of treatment as has also been reported for other neuroleptics.Three weeks of treatment with clozapine induces a selective inhibition of the active DA neurones in VTA but at much higher doses than seen with sertindole, while haloperidol induces a non‐selective decrease of spontaneously active DA neurones in both areas.In acute electrophysiological experiments intraveneous (i.v.) administration of sertindole—in contrast to both clozapine and haloperidol—neither reverse d‐amphetamine‐ nor apomorphine‐induced inhibition of the firing frequencies of DA neurones in SNC or in VTA. In addition, sertindole does not—even in high doses—increase the firing frequency of DA neurones in SNC or VTA.In conclusion the study indicates that sertindole is a potential antipsychotic compound which should induce fewer extrapyramidal side‐effects than seen after classical neuroleptics.
Differential effects of amfonelic acid on the haloperidol‐ and clozapine‐induced increase in extracellular dopac in the nucleus accumbens and the striatum
Authors: Rivest Robert , Marsden Charles A. 
Published: December 2004

AbstractThis study compares the effects of the nonamphetamine stimulant amfonelic acid on the increase in extracellular 3,4‐dihydroxyphenylacetic acid (DOPAC) induced by haloperidol and clozapine in the nucleus accumbens and the striatum of anaesthetized rats. DOPAC was simultaneously recorded in both regions using differential pulse voltammetry with electrically pretreated carbon fibre electrodes. Amfonelic acid (2.5 mg/kg s.c.) did not alter basal striatal DOPAC but produced a significant reduction in extracellular DOPAC in the nucleus accumbens. Haloperidol (1 mg/kg s.c.) increased extracellular DOPAC in both regions. When amfonelic acid was injected 5 min before haloperidol, the increase in DOPAC was potentiated in both the nucleus accumbens and the striatum but with a greater effect in the striatum. Clozapine (30 mg/kg i.p.) increased extracellular DOPAC in both regions, an effect partially attenuated by amfonelic acid in both regions but to a greater extent in the striatum. When ritanserin (5 mg/kg i.p.), a serotonergic antagonist (5‐HT‐2), was co‐administered with haloperidol, the potentiation by amfonelic acid of the increase in extracellular DOPAC induced by haloperidol was attenuated in both the nucleus accumbens and the striatum. The present results confirm that amfonelic acid can be used to discriminate neurochemically between haloperidol and clozapine in vivo. The effects of amfonelic acid on the neuroleptic‐induced changes in extracellular DOPAC were greater in the striatum than the nucleus accumbens. These results further demonstrate that both neuroleptics increase dopamine metabolism in the two brain regions but by different mechanisms, supporting the view that the regulation of dopamine metabolism differs in the two regions. Furthermore, the interaction between amfonelic acid and clozapine suggests that the increase in dopamine metabolism induced by the atypical neuroleptic results from the blockade of both dopaminergic and nondopaminergic receptors and may include the sertonergic (5‐HT‐2) receptors.
Autoradiographic localization of 5HT1 binding sites in autonomic areas of the rat dorsomedial medulla oblongata
Authors: Thor Karl B. , Blitz‐Siebert Alisa , Helke Cinda J. 
Published: December 2004

AbstractSerotonin (5HT) binding sites in autonomic portions of the dorsomedial medulla oblongata of the rat were localized using autoradiographic techniques with radioactive ligands that express high affinity for the 5HT1 (3H‐5HT), 5HT1A (3H‐8OH‐DPAT), or 5HT1B (125I‐CYP with isoproterenol) receptor subtypes. 5HT1A sites were densely distributed in the nucleus tractus solitarius (NTS), with the highest densities localized to the interstitial subnucleus and the central subnucleus. 5HT1B sites were also found in the NTS, with the highest densities localized to the substantia gelatinosa subnucleus. The dorsal motor nucleus of the vagus nerve and nucleus ambiguus exhibited low densities of 5HT1B sites. However, the nucleus intercalatus, a cerebellar relay nucleus that also contains dendrites of vagal parasympathetic preganglionic neurons and receives autonomic forebrain afferent input, showed very dense 5HT1B sites. The promontorium, paratrigeminal islands, and the dorsomedial portion of the trigeminal nucleus (DM5), which are areas of viscerosomatic integration, exhibited high densities of both 5HT1A and 5HT1B sites. The area postrema contained low levels of both 5HT1A and 5HT1B sites.Visceral deafferentation via cervical vagotomy or nodose ganglionectomy caused a significant decrease in 5HT1A sites in the interstitial subnucleus of the NTS ipsilateral to the lesion. No changes were seen in 5HT1B sites.These studies suggest that 5HT1A and 5HT1B sites are involved in the processing of visceral sensory information in the NTS and associated areas. Based upon viscerotopic organization of the NTS, 5HT1A sites appear preferentially distributed in portions of the NTS that are associated with the coordination of swallowing, respiration, and cardiovascular function, while 5HT1B sites appear preferentially distributed in areas of the NTS associated with gastrointestinal, hepatic, pancreatic, and cardiovascular function. However, since these associations were not absolute and there was a great deal of overlap between the two sites, speculation regarding their specific functions in autonomic control must await pharmacological examination.
Regional distribution and kinetics of haloperidol binding in human brain: A pet study with [18F]haloperidol
Authors: Schlyer David J. , Volkow Nora D. , Fowler Joanna S. , Wolf Alfred P. , Shiue Chyng‐Yann , Dewey Stephen L. , Bendriem Bernard , Logan Jean , Raulli Robert , Hitzemann Robert , Brodie Jonathan , Alavi Abass A. , MacGregor Robert R. 
Published: December 2004

AbstractThe regional distribution and the kinetics of haloperidol uptake in human brain were examined using [18F]haloperidol and PET in 9 controls and 5 schizophrenics while on haloperidol medication and after haloperidol washout. The regional distribution of [18F]N‐methylspiroperidol, a tracer for D2 receptors, was measured in 1 normal subject for comparison. The uptake of [18F]haloperidol in the whole brain in normals was high (6.6% of the injected dose at 2 hr), and regional distribution was much more extensive than could be accounted for by the distribution of dopamine D2 receptors. In normals, the cerebellum, basal ganglia, and thalamus showed a greater concentration than the cortex, and there was minimal clearance of 18F from the brain during the 10‐hr period of the study. Medicated schizophrenics showed a total brain uptake of 4.0% and had a significant clearance of [18F]haloperidol from brain and a higher concentration of [18F]haloperidol in plasma. After withdrawal from medication. These results are discussed in terms of the pharmacokinetics of haloperidol in the human brain and its binding to dopamine D2 receptors and to sigma receptors. © 1992 Wiley‐Liss, Inc.
Within‐subject sensitization of striatal dopamine release after a single injection of cocaine: An in vivo microdialysis study
Authors: Keller Richard W. , Maisonneuve Isabelle M. , Carlson Jeffrey N. , Glick Stanley D. 
Published: December 2004

AbstractRepeated microdialysis measurements, conducted 1 week apart at the same tissue site, were used to investigate the changes in basal and cocaine‐stimulated extracellular dopamine (DA) levels after a single prior exposure to either saline or cocaine. Dialysis probes were placed into rats previously implanted with guide cannulas and basal levels of dopamine (DA), and its metabolites (DOPAC and HVA) were estimated in 20‐min fractions of the dialysate. Basal levels in the extracellular fluid (ECF), estimated from pre‐implantation calibration of the probes, were 7.9 ± 0.7 nM DA, 4.9 ± 0.8 μM DOPAC, and 3.6 ± 0.6 μM HVA. After a stable baseline was obtained saline (1 ml/kg, i. p.) or cocaine (20 mg/kg, i. p.) was injected. Saline produced no significant changes in any of the neurochemical markers. A cocaine injection produced a sixfold increase in DA, while DOPAC and HVA were unchanged. One week later the same procedure was repeated except this time both groups received cocaine. In rats that had received cocaine 1 week earlier, basal DA levels in the ECF were doubled, whereas they were unchanged in rats that received saline a week earlier. Furthermore, the dopamine release in response to acute cocaine during the second week was elevated in animals which had been previously exposed to cocaine. Rotation was also measured during both weeks and, while a tendency toward behavioral sensetization was observed, it did not reach significance. Thus, a single exposure to cocaine, while not sufficient to induce behavioral sensitization in these rats, was sufficient to produce an elevated basal DA level and a sensitization of cocaine‐stimulated DA release when in vivo microdialysis measurements were repeated within the same rat. © Wiley‐Liss, Inc.
Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem
Authors: Arvidsson Ulf , Cullheim Staffan , Ulfhake Brun , Ramírez Vania , Dagerlind Å;ke , Luppi Pierre‐Hervé , Kitahama Kunio , Jouvet Michel , Terenius Lars , Åman Katarina , Hökfelt Tomas 
Published: December 2004

AbstractThe distribution of enkephalin (ENK)‐like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP)techniques. Possible coexistence between ENK‐ and 5‐hydroxytryptamine (5‐HT)‐LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK.ENK‐immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK‐IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co‐localization between ENK‐ and 5‐HT‐LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK‐LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected.In the brain stem of cats after colchicine treatment, ENK‐LI was found in a majority of the 5‐HT‐IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK‐IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK‐IR cell bodies could be seen in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei.It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels. In the cat there is a discrepancy between the low degree of coexistence with 5‐HT observed in terminals in the spinal cord and the extensive coexistence in presumed cell bodies of origin in the medulla of colchicine treated animals. One possible explanation for this is that the expression of ENK in raphe neurons under normal circumstances is very low but that colchicine induces an upregulation of the synthesis of this peptide. © Wiley‐Liss, Inc.
Muscarinic M2‐selective ligands also recognize M4 receptors in the rat brain: Evidence from combined in situ hybridization and receptor autoradiography
Authors: Vilaró M. Teresa , Wiederhold Karl‐Heinz , Palacios José M. , Mengod Guadalupe 
Published: December 2004

AbstractWe have used autoradiographic techniques to examine the characteristics and distribution of the binding of reported selective M2 muscarinic ligands and compared them with the distribution of cells expressing mRNAs for the different subtypes of muscarinic receptors. Our results suggest that the M2 ligands used in the present study ([3H]OXO‐M, [3H]AF‐DX 384, AF‐DX 116, methoctramine) also recognize M4 receptors present in regions such as the striatum and olfactory tubercle. This is supported by (1) relative abundances of the different transcripts, with m2 mRNA being very scarce and m4 mRNA very abundant in these regions; (2) comparison of the pharmacological characteristics of M2‐ligand binding sites in brain areas selected by their exclusive expression of M2 receptors versus areas enriched in M4 receptors. An important conclusion of these studies is that none of the muscarinic radioligands available at the present time appears to label specifically a single muscarinic receptor subtype population. Areas are suggested where autoradiographic techniques can be helpful in elucidating the subtype selectivity of existing and new ligands. © Wiley‐Liss, Inc.
Acute stress impairs (or induces) synaptic long‐term potentiation (LTP) but does not affect paired‐pulse facilitation in the stratum radiatum of rat hippocampus
Authors: Shors Tracey J. , Thompson Richard F. 
Published: December 2004

AbstractRats were exposed to restraint coupled with 60, 1‐sec, 1‐mA, 60‐Hz tail shocks. One hippocampus was immediately dissected for in vitro measurement of pairedpulse facilitation and LTP of the excitatory postsynaptic potential (EPSP) recording from the stratum radiatum of field CA1. There was no change in paired‐pulse facilitation, suggesting that acute exposure to the stressor does not result in a decrease in presynaptic neurotransmitter release. There was, however, a significant decrease in the percent LTP produced by theta burst stimulation relative to naïve controls. These results are consistent with the hypothesis that the stress‐induced impairment of LTP is a result of changes in the postsynaptic glutamate receptors, specifically the AMPA type. © Wiley‐Liss, Inc.
Acute effects of Sigma ligands on the electrophysiological activity of rat nigrostriatal and mesoaccumbal dopaminergic neurons
Authors: Zhang Jing , Chiodo Louis A. , Wettstein Joseph G. , Junien Jean‐Louis , Freeman Arthur S. 
Published: December 2004

AbstractThe effects of acute i. v. administration of several sigma ligands on the single‐unit activity of nigrostriatal and mesoaccumbal dopaminergic (DA) neurons were evaluated in chloral hydrate‐anesthetized rats. DTG (1, 3‐di(o‐tolyl)guanidine) did not alter DA neuronal activity at nontoxic doses and JO 1784 [(+)‐N‐cyclopropylmethyl‐N‐methyl‐1, 4‐diphenyl‐1‐ethylbut‐3‐en‐1‐ylamine] was inactive. (+)‐Pentazocine was more effective in increasing mesoaccumbal vs. nigrostriatal DA cell firing rates. BMY 14802(α‐(4‐fluorophenyl)‐4‐(5‐fluoro‐2‐pyrimidinyl)‐1‐piperazine‐butanol) dose‐dependently increased DA cell firing rate in both populations. The inhibition of nigrostriatal DA cell firing rate by (+)‐3‐(3‐hydroxyphenyl)‐N‐(1‐propyl)piperidine [(+)‐3‐PPP] was reversed by(−)‐eticlopride and (+)‐but not (−)‐butaclamol, which supports previous evidence that (+)‐3‐PPP‐induced inhibition is due to the DA agonist properties of the drug. From what is known of the pharmacological properties of these compounds, it is concluded that acute sigma receptor occupation does not markedly alter the firing rate of DA neurons. The dose‐response curve for inhibition of nigrostriatal DA neuronal activity by the D2 DA agonist, quinpirole, was shifted to the right tenfold by BMY 14802 pretreatment (8mg/kg, i. v.) and twofold by (+)‐pentazocine (8 mg/kg, i. v.), but was not changed by DTG (2 mg/kg, i. v.). It is concluded that the marked effects of certain sigma ligands on DA cell electrophysiology are likely due to their non‐sigma properties. © Wiley‐Liss, Inc.
Perforated synapses are present during synaptogenesis in rat neocortex
Authors: Itarat W. , Jones D. G. 
Published: December 2004

AbstractIt has been known for some time that perforated synapses increase in number and size with increasing age. Initially, these trends were used to support the concept that nonperforated synapses anlarge until an optimal size is reached, at which point they perforate and may subsequently split. More recent stereological and threedimensional reconstruction investigations, however, suggest that this may not be the case and that perforated and nonperforated synapses constitute separate synaptic populations. In order to test the separate population hypothesis, synapses have been studied ultrastructurally in the parietal cortex of rats aged 19 and 20 days gestation, and 1 and 4 days postnatal. By examining synapses serially, and also by studying three‐dimensional reconstructions, it has been demonstrated that perforated synapses are present at each of these ages. Some are relatively simple in organization, resembling previously described perforated synapses at 14 days of age, although others appear to consist of two or more separate PSD components. These findings demonstrate that perforated synapses are present from early on in synaptogenesis and that developing perforated synapses are present from early on in synaptogenesis and that developing perforated synapses may have distinct characteristics that cast light on their developmental course. © Wiley‐Liss, Inc.
Effects of high‐dose methamphetamine on monoamine uptake sites in rat brain measured by quantitative autoradiography
Authors: Brunswick David J. , Benmansour Saloua , Tejani‐Butt Shanaz M. , Hauptmann Miroslawa 
Published: December 2004

AbstractThe neurotoxicity of methamphetamine to monoaminergic neurons was examined. Neurotoxicity was assessed by quantitative autoradiography using radioligands specific for binding to norepinephrine, dopamine, and serotonin uptake sites. High‐dose administration of methamphetamine led to decreases in binding to uptake sites for the three monoamines. Norepinephrine binding sites were decreased in certain amygdaloid nuclei and in the dorsomedial hypothalamic nucleus. Serotonin binding sites were reduced in widespread brain areas, while dopamine binding sites were reduced in the caudate putamen, olfactory tubercle, and nucleus accumbens. The decreases in binding site density for the three monoamines are limited to terminal field areas; cell body areas are not affected. Our results indicate that methamphetamine is neurotoxic to serotonin, dopamine, and norepinephrine neurons. The neurotoxicity to norepinephrine neurons is in selected brain areas. © Wiley‐Liss, Inc.
Enhanced hydroxyl radical generation by 2′‐methyl analog of MPTP: Suppression by clorgyline and deprenyl
Authors: Chiueh C. C. , Huang S.‐J. , Murphy D. L. 
Published: December 2004

AbstractSodium salicylate was infused through a microdialysis probe placed in the striatum of anesthetized rats in order to assay the formation of hydroxyl radical (.OH) in the extracellular fluid in vivo. In addition to causing sustained dopamine relese, intrastriatal infusion of the 2′‐methyl analog of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropridine (2′CH3‐MPTP) increased the formation of 2,3‐dihydroxybenzoic acid (2,3‐DHBA), the nonenzymatic. OH adduct of salicylate in the brain dialysate. Inhibition of monoamine oxidase (MAO) by clorgyline and deprenyl completely blocked the formation of 2,3‐DHBA and the sustained dopamine overflow induced by 2′‐CH3‐MPTP. The results indicate that the enhanced formation of cytotoxic. OH by 2′‐CH3‐MPTP is suppressed by MAO inhibitors. These data support the hypothesis that the protective effect of MAO inhibitors on the neurotoxicity induced by MPTP analogues may be due not only to the inhibition of MPTP metabolism by MAO but also the blockade of the formation of OH free radicals. An enhanced generation of cytotoxic. OH free radicals in the striatum which in turn leads to oxidant damage may be relevant to the development of parkinsonism‐like changes in animals produced by MPTP analogues. © Wiley‐Liss, Inc.
Quantitation of Carbon‐11‐labeled raclopride in rat striatum using positron emission tomography
Authors: Hume Susan P. , Myers Ralph , Bloomfield Peter M. , Opacka‐Juffry Jolanta , Cremer Jill E. , Ahier Randall G. , Luthra Sajinda K. , Brooks David J. , Lammertsma Adriaan A. 
Published: December 2004

AbstractUsing conventional autoradiographic and tissue counting techniques, the experimental quantitation of in vivo kinetics of prospective or established radioligands for PET is animal and labour intensive. The present study tested the feasibility of using PET itself to quantitate the specific binding of [11C] raclopride to rat striatum and to study the effects of experimental manipulation of endogenous dopamine on binding parameters.Carbon‐11‐labeled raclopride was given i. v. to anaesthetised rats, positioned in a PET camera and dynamic emission scans acquired over 60 min. Time‐activity curves were generated for selected regions of interest, representing striatum and cerebellum and the striatal data fitted to a compartmental model, using cerebellum as the input function, thus circumventing the need for individual metabolite‐corrected plasma curves. In control rats, the binding potential (BP), defined as the ratio of the rate constants for transfer from “free to bound” and “bound to free” compartments, was of the order of 0.6. This was reduced threefold by predosing with nonraioactive raclopride. Increasing extracellular dopamine levels by predosing with d ‐amphetamine resulted in a significant decrease in BP whereas reducing extracellular dopamine by predosing with γ‐butyrolactone caused a significant increase.Thus, despite the limitation in spatial resolution of PET, specific binding of raclopride could be assessed from regional time‐activity curves from individual rats. The system was sufficiently sensitive that changes in BP could be detected following modulation of endogenous dopamine levels, a finding of potential relevance to the interpretation of clinical PET data.