bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distribution of beta‐adrenergic receptor subtypes in human post‐mortem brain: Alterations in limbic regions of schizophrenics
Authors: Joyce Jeffrey N. , Lexow Nedra , Kim Soo Jin , Artymyshyn Roman , Senzon Shari , Lawerence David , Cassanova Manuel F. , Kleinman Joel E. , Bird Edward D. , Winokur Andrew 
Published: December 2004

AbstractThe distribution of the beta1 (β1) and beta2 (β2) subtypes of the β‐adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the β1 and β2 receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [125I]iodopindolol (IPIN) to cortical membranes showed a similar Kd in human (177 pM) and rat (161 pM), but a lower maximum binding site (Bmax) in the human tissue (18.7 fmol/mg protein and 55.6 fmol/mg protein). For the autoradiographic studies [125I]IPIN was used to visualize both subtypes (total) or was displaced with the selective β1‐receptor antagonist ICI‐89,406 to visualize β2 sites, or with the selective β2‐receptor antagonist ICI‐118,551 to visualize β1 sites. Important differences in the regional distribution of the two subtypes of the β‐adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of β1 receptors was observed that was not evident in the rat. These patches were aligned with markers of the matrix compartment of the striatum. The schizophrenic cases showed significant increases in the labeling of the β1‐receptor patches with [125I]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of β1 to β2 receptors and a highly laminar organization of the subtypes. [125I]IPIN binding to β1 receptors was highest in the external laminae with the reverse gradient for the β2 subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the β‐adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the β2 receptor. Moreover, there were consistently higher densities of β2 receptors in the hippocampus of the right hemisphere than the left hemisphere of the nondisease controls. There was not a left and right hemispheric asymmetry of β2 receptors in the hippocampus of elderly schizophrenics or in young schizophrenics who committed suicide. The asymmetry was evident in nonschizophrenic suicides, suggesting that the lack of asymmetry in the hippocampus of schizophrenics is evident early in the disease process. Thus limbic structures show alterations in the patterning of β1 and β2 receptors in the schizophrenic cases.
Pharamacological characterization of excitaory synaptic potentials in rat basolateral amygdaloid neurons
Authors: Gean Po‐Wu , Chang Fang‐Chia 
Published: December 2004

AbstractThe pharmacological properties of synaptic responses in rat basolateral amygdaloid (BLA) neurons were studied using intracellular recording techniques. Three distinct types of synaptic potential were evoked by stimulation of the adjacent ventral endopyriform nucleus: (1) a fast excitatory postsynaptic potential (f‐EPSP);(2) a late EPSP (1‐EPSP) following the f‐EPSP; and (3) a multiphasic hyperpolarization following the initial depolarizing potential. Superfusion of 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX), a selective non‐N‐methyl‐D‐aspartate (non‐NMDA) receptor antagonist, blocked the f‐EPSP in a concentration‐dependent manner. The ED50 for this effect was around 4 m̈M. In the presence of CNQX, however, a small depolarizing potential remained. This residual depolarizing component was markedly enhanced on removing Mg++ from the perfusing medium and could subsequently be abolished by DL‐2‐amino‐5‐ phosphonovaleate (DL‐APV, 50 m̈M) indicating its mediation via NMDA receptor‐coupled ionophore. The l‐EPSP was reversibly blocked by DL‐APV. These results suggest that the pyriform cortex‐amygdala pathway is mediated through excitatory amino acids acting on non‐NMDA as well as NMDA receptors located on the BLA neurons.
Neonatal 6‐OHDA Lesions differentially affect striatal D1 and D2 receptors
Authors: Neal Bethany S. , Joyce Jeffrey N. 
Published: December 2004

AbstractLesions to the dopamine (DA) system in early postnatal development have different behavioral consequences compared to lesions made in adulthood. Intrastriatal injections of the neurotoxin 6‐hydroxydopamine (6‐OHDA) on the day of birth (PO) or postnatal day 1 (P1) produce a selective supersensitivity to D1 receptor agonists and a subsensitivity to D1 antagonists (Neal and Joyce, 1991a). In this paper, we describe the long‐term effects of early DA loss on DA receptor regulation. Pups received bilateral intrastriatal injections of the neurotoxin 6‐OHDA (4 m̈g per striatum) on PO or P1. Adult rats were killed at 90 days of age and the brains were processed for quantitative autoradiography (QAR) or tyrosine hydroxylase (TH) immunocytochemistry. Cohorts were tested for the behavioral responses to the selective D1 receptor agonist SKF38393 (10 mg/kg). Neonatally lesioned rats exhibited increases in abnormal perioral movements in response to D1 receptor stimulation. There was a heterogenous and patchy loss (40–50%) of [3H]mazindol binding to high‐affinity DA uptake sites (a marker of DA terminal density) and a similar loss of TH‐like immunoreactivity within the striata of the neonatally lesioned rats. There was also a reduction in the number of ð‐opioid receptor patches (labelled with [3H] naloxone), a marker for the striatal patch compartment, and a similar patchy loss of D1 binding sites (labelled with [3H]SCH23390). The binding of [3H]spiroperidol to D2 sites was not altered. This is in contrast to the changes observed following adult 6‐OHDA lesions, wherein there is a significant increase in the number of D2 binding sites (Joyce, 1991a, b). The results are discussed with respect to the behavioral consequences of neonatal lesions and the differences between neonatal and adult lesions. © 1992 Wiley‐Liss, Inc.
Membrane‐Bound and solubilized brain 5HT3 receptors: Improved radioligand binding assays using bovine area postrema or rat cortex and the radioligands 3H‐Gr65630C, 3H‐BRl43694, and 3H‐LY278584
Authors: Miller Keith , Weisberg Ellen , Fletcher Paul W. , Teitler Milt 
Published: December 2004

AbstractBovine area postrema tissue was used as a convenient source of tissue for studies of brain 5HT3 receptor density was determined to be 97 ± 5 fmol/mg and 124 ± 10 fmol/mg of protein using the commercially available 5HT3 radioligands, 3H‐GR65630 and 3H‐BRL43694, respectively. The equilibrium dissociation constants (KD) for 3H‐GR65630 and 3H‐BRL43694 were 0.5 ± 0.1 nM and 1.7 ± 0.3 nM, respectively. The affinities of a series of drugs for the 5HT3 receptor using the two radioligands were essentially identical; the Ki values and order of affinities of agonists and antagonists were very similar to data published in studies on radiolabeling of 5HT3 receptors in rat brain. 3H‐LY278584 also labeled 5HT3 receptors in bovine area postrema homogenates with a KD of 3.1 ± 0.1 nM and a Bmax of 84 ± 6 fmol/mg. In rat cortical homogenates, 3H‐LY278584 produced the most reliable specific signal of 72%, with a KD of 2.6 ± 0.3 nM and a Bmax value of 10.5 ± 1 fmol/mg. At 1 nM, 3H‐GR65630 or 3H‐BRL43694 specific binding represented 28 and 50% of total radioligand binding, respectively. These data in bovine and rat brain tissues indicate that bovine area postrema can be used with 3H‐GR65630, 3H‐BRL43694, or 3H‐LY278584 can be used for studies on the regulation and/or the molecular properties of 5HT3 receptors in rat cortical homogenates. 5HT3 receptors were solubilized from bovine area postrema and characterized using 3H‐GR65630. Gel filtration chromatography revealed a specific binding peak with a MW of approximately 600 kDa. A 10‐fold enrichment of the binding activity was achieved using wheat germ agglutinin followed by application of N‐acetyl‐glucosamine to elute the glycosylated proteins, indicating the receptor is a glycosylated protein. © Wiley‐Liss, Inc.
Synaptic organization of the serotoninergic input to the superficial gray layer of the hamster's superior colliculus
Authors: Arce Erick A. , Bennett‐Clarke Carol A. , Mooney Richard D. , Rhoades Robert W. 
Published: December 2004

AbstractImmunocytochemistry with an antibody directed against a serotonin (5‐HT)‐bovine serum albumin (BSA) conjugate was combined with electorn microscopy and serial section analysis to examine the synaptic organization of the serotoninergic projection to the stratum griseum superficale (SGS) of the hamster's superior colliculus (SC). Most of the 5‐HT‐immunoreactive swellings in the hamster's SC did not make conventional synaptic contacts. Examination of 250 such swellings in single thin sections revealed only 11 synapses. Assessment of an additional 50 swellings followed through serial sections showed that only 6% (N = 3) of these varicosities made conventional synaptic contacts. All the synapses made by serotoninergic axons were with the dendrites of SC neurons. These results demonstrate that the inhibitory effects of 5‐HT on SC neurons in hamster are mainly mediated by the nonsynaptic release of this indoleamine. © Wiley‐Liss, Inc.
Feedback inhibition of met‐enkephalin release from the rat spinal cord in vivo
Authors: Collin E. , Bourgoin S. , Mantelet S. , Hamon M. , Cesselin F. 
Published: December 2004

AbstractThe possible exitence of a feedback control by endogenous opioids of the spinal release of met‐enkephalin‐like material was assessed in vivo, in halothane‐anesthetized rats whose intrathecal space was continuously perfused with an artifical cerebrospinal fluid supplemented with various opioid‐related drugs. Both the intrathecal perfusion of the μ agonist D‐Ala2‐D‐MePhe4‐Gly‐ol5‐enkephalin (DAGO) (10 μM) and the ∂ agonist Tyr‐D‐Thr‐Gly‐Phe‐Leu‐Thr (DTLET) (10 μM) produced a significant inhibition of the spinal outflow of met‐enkephalin‐like material. The effect of DAGO, but not that of DTLET, could be prevented by naloxone (10 μM), and, conversely, the effect of DLTET, but not that of DAGO, was no longer observed in the presence of naltrindole (10 μM). Therfore naloxone and naltrindole acted as potent and selective μ and ∂ antagonists, respectively, when perfused at 10 μM in the intrathecal space of halothane‐anesthetized rats. As expected from the lack of a tonic opioid control of spinal enkephalinergic neurones, neither naloxone nor naltrindole alone affected the spontaneous outflow of metenkephalin‐like material. However, naltrindole, but not naloxone, markedly increased the spinal overflow of met‐enkephalin‐like material due to intrathecal administration of either porcine calcitonin (10 μM) or the peptidase inhibitors thiorphan (10 μM) plus bestatin (20 μM). These data suggest that μ, but not ð, receptors are involved in a phasic opioid inhibitory control of the release of met‐enkephalin‐like material in the rat spinal cord. This control would be functional only when the concentration of extracellular endogenous opioid(s) reaches a critical level, as probably occurring in pain‐suffering subjects. ð Opioid antagonists acting selectively on the receptors involved in this feedback control might constitute a new class of analgesic drugs. © 1992 Wiley‐Liss, Inc.
Chronic cocaine enhances serotonin autoregulation and serotonin uptake binding
Authors: Cunningham Kathryn A. , Paris Joseph M. , Goeders Nick E. 
Published: December 2004

AbstractRepeated cocaine intoxication can result in the development of behavioral sensitization in animals and psychosis in humans, phenomena that have been associated with alterations in dopamine (DA) function. Using electrophysiologic and autoradiographic techniques, modifications of central serotonin (5‐hydroxytryptamine; 5‐HT) systems were investigated in rats treated with a regimen of cocaine administration that produced behavioral sensitization. The inhibitory response of single 5‐HT neurons in the dorsal raphe (DR) to (−)‐cocaine, the 5‐HT uptake inhibitor fluoxetine or the 5‐HT1A agonist 8‐hydroxy‐2‐[di‐N‐propylamino]tetralin (8‐OHDPAT) was significantly enhanced in cocaine‐treated rats. Furthermore, several brain areas that contain either cell bodies (DR) or terminals for 5‐HT (medial and sulcal prefrontal cortex, frontal cortex) showed cocaine‐induced elevations in [3H]imipramine‐labeled 5‐HT uptake sites, while [3H]‐8‐OHDPAT‐labeled 5‐HT1A receptors were decreased only in the central medial amygdala. These results suggest that modifications of autoregulatory mechanisms secondary to alterations of 5‐HT uptake processes may contribute to the development of cocaine sensitization. © Wiley‐Liss, Inc.
Effects of nigrostriatal lesions on the levels of messenger RNAs encoding two isoforms of glutamate decarboxylase in the globus pallidus and entopeduncular nucleus of the rat
Authors: Soghomonian Jean‐Jacques , Chesselet Marie‐Francoise 
Published: December 2004

AbstractThe neurotransmitter γ‐aminobutyric acid (GABA) is present in efferent neurons of the striatum and of the pallidum, one of the main striatal target areas. Dopaminergic nigrostriatal neurons play a critical role in the regulation of GABAergic neurotransmission in the striatum. In the present study, we investigated their role in the regulation of glutamate‐decarboxylase (GAD) mRNA expression in two divisions of the pallidum in rats: the globus pallidus and entopeduncular nucleus, equivalent to the external and internal pallidum, respectively, of primates. Dopaminergic neurons were lesioned by unilateral injections of 6‐hydroxydopamine (6‐OHDA) in the substantia nigra of adult rats. Two or 3 weeks after the lesion, frontal cryostat‐cut sections of the brain were processed for in situ hybridization histochemistry with 35S‐labeled RNA probes synthesized from cDNAs encoding two distinct isoforms of GAD of respective molecular weight 67,000 (GAD67) and 65,000 (GAD65). The number of labeled cells was determined, and intensity of labeling in individual cells was analyzed by computerized image analysis on emulsion radioautographs.In the globus pallidus, the number of labeled neurons and intensity of labeling per cell were increased on the side ipsilateral to the lesion as compared with control rats in sections hybridized with the GAD67 RNA probe. No changes were detected on the side contralateral to the lesion or in the levels of labeling for GAD65 mRNA. Confirming previous data, the level of labeling for GAD65 mRNA was much higher than for GAD67 mRNA in the entopeduncular nucleus of control rats. In rats with a 6‐OHDA lesion, labeling for both GAD67 and GAD65 mRNAs was decreased on the side contralateral, but not ipsilateral, to the lesion, as compared with control rats.The results show that lesions of the nigrostriatal pathway in rats affect the levels of mRNAs encoding two distinct isoforms of GAD in neurons of the globus pallidus and entopeduncular nucleus differently. In addition, results in the entopeduncular nucleus further support a bilateral effect of unilateral dopaminergic lesions. © 1992 Wiley‐Liss, Inc.
[123/125I]RTI‐55, an in vivo label for the serotonin transporter
Authors: Scheffel Ursula , Dannals Robert F. , Cline Elizabeth J. , Ricaurte George A. , Carroll F. Ivy , Abraham Philip , Lewin Anita H. , Kuhar Michael J. 
Published: December 2004

Abstract[123I]RTI‐55, an iodinated derivative of the cocaine analog 3β‐phenyltropane‐2β‐carboxylic acid methyl ester, was evaluated as an agent for in vivo labeling of the serotonin transporter. Labeling of the precursor of RTI‐55 with I‐123 was efficient and yielded a high specific activity product. After intravenous injection of [123I]RTI‐55 into rats, the tracer accumulated in regions with high densities of serotonin and dopamine uptake sites. The distribution of [123I]RTI‐55 binding in areas rich in serotonin uptake sites correlated with [3H]serotonin uptake measured in vitro in the same regions. Specific [123I]RTI‐55 binding to serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909. Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66% (in the hypothalamus) to 83% (in the superior colliculi) of specific [125I]RTI‐55 binding in all areas except in the striatum and the olfactory tubercles (regions rich in dopamine transporters). These results indicate that [123/125I]RTI‐55 binds, although not selectively, to the serotonin transporter in vivo. Furthermore, they suggest that [123I]RTI‐55 holds promise as a SPECT imaging agent for the study of the serotonin transporter in humans in health and disease. Published Wiley‐Liss, Inc.
Topographic nonoverlapping distribution of D1 and D2 dopamine receptors in the amygdaloid nuclear complex of the rat brain
Authors: Scibilia Richard J. , Lachowicz Jean E. , Kilts Clinton D. 
Published: December 2004

AbstractThe distribution of D1 and D2 dopamine (DA) receptors in the nuclei and subnuclear zones of the rat amygdaloid complex was mapped using quantitative light microscopic autoradiography. [125I]iodosulpiride and [125I]SCH 23982 (in the presence of 50 nM ketanserin) were used to label D2 and D1 DA receptors, respectively. The DA receptor subtypes exhibited a topographic, nonoverlapping distribution which generally conformed to the cytoarchitectonic boundaries of the component nuclei and subnuclear zones of the amygdaloid complex. The highest density of [125I]iodosulpiride binding sites was observed in the main intercalated cell group and the central amygdaloid nucleus where a medial to lateral gradient of binding sites was localized to its subnuclear zones. [125I]SCH 23982 binding sites were localized in the main intercalated cell group and the basolateral amygdaloid nucleus with a uniform low density in the central nucleus. The functional topography of mesoamygdaloid DA neurons may therefore be mediated, in part, at the level of DA receptor subtypes. The pattern of distribution of [125I]iodosulpiride binding sites in subdivisions of the central amygdaloid nucleus and bed nucleus of the stria terminalis suggests that the functions of the “extended amygdala,” a major system of the functional organization of the basal forebrain, may be regulated by DA afferents at multiple key sites of D2 receptor action. © Wiley‐Liss, Inc.
MK‐801 protection against methamphetamine‐induced striatal dopamine terminal injury is associated with attenuated dopamine overflow
Authors: Weihmuller Fredric B. , O'Dell Steven J. , Marshall John F. 
Published: December 2004

AbstractRepeated administrations of methamphetamine (m‐AMPH) produce high extracellular levels of dopamine (DA) and subsequent striatal DA terminal damage. Pharmacological blockade of N‐methyl‐D‐aspartate (NMDA) receptors has been shown previously to prevent m‐AMPH‐induced striatal DA terminal injury, but the mechanism for this protection is unclear. In the present study, in vivo microdialysis was used to determine the effects of blockade of NMDA receptors with the noncompetitive antagonist MK‐801 on m‐AMPH‐induced striatal DA overflow. Four injections of MK‐801 (0.5 mg/kg, ip) alone did not significantly change extracellular striatal DA concentrations from pretreatment values. Four treatments with m‐AMPH (4.0 mg/kg, sc at 2‐hr intervals) increased striatal DA overflow, and the overflow was particularly extensive following the fourth injection. This m‐AMPH regimen produced a 40% reduction in striatal DA tissue content 1 week later. Treatment with MK‐801 15 min before each of the four m‐AMPH injections or prior to only the last two m‐AMPH administrations attenuated the m‐AMPH‐induced increase in striatal DA overflow and protected completely against striatal DA depletions. Other MK‐801 treatment regimens less effectively reduced the m‐AMPH‐induced striatal DA efflux and were ineffective in protecting against striatal DA depletions. Linear regression analysis indicated that cumulative DA overflow was strongly predictive (r = −.68) of striatal DA tissue levels measured one week later. These findings suggest that the extensive DA overflow seen during a neurotoxic regimen of m‐AMPH is a crucial component of the subsequent neurotoxicity. Blockade of NMDA receptors with MK‐801 apparently prevents damage to DA neurons by attenuating this stimulant‐induced DA overflow. © Wiley‐Liss, Inc.
Regional norepinephrine response to amphetamine using dialysis: Comparison with caudate dopamine
Authors: Kuczenski Ronald , Segal David S. 
Published: December 2004

AbstractThe response of extracellular norepinephrine to the acute administration of amphetamine was assessed, using dialysis, in prefrontal cortex and hippocampus in awake, behaving rats. Norepinephrine exhibited a pronounced and rapid dose‐ and time‐dependent increase in response to 0.5 and 2.5 mg/kg amphetamine, which corresponded closely to the time course of the behavioral profile. These results are consistent in with a possible role for norepinephrine in the behavioral response to amphetamine. © Wiley‐Liss, Inc.
ATP‐Sensitive K+ channels mediate an IPSP in dorsal horn neurones elicited by sensory stimulation
Authors: Salter Michael W. , De Koninck Yves , Henry James L. 
Published: December 2004

AbstractNociceptive dorsal horn neurones, which are involved in the processing of pain‐related information, are inhibited by input from vibration‐sensitive, large diameter primary sensory fibres (Wall and Cronly‐Dillon, 1960; Salter and Henry, 1990a, b). We have reported previously that the inhibition of spinal nociceptive neurones by vibration is mediated by adenosine acting through P1‐purinergic receptors (Salter and Henry, 1987). In a number of different types of cell, adenosine is known to activate K+ currents (Gerber et al., 1989; Greene and Haas, 1985; Proctor and Dunwiddie, 1987; Segal, 1982; Trussell and Jackson, 1987) and we have recently found that the adenosine‐mediated inhibition of nociceptive neurones by vibration is the result of an inhibitory postsynaptic potential (IPSP), which is, indeed, caused by a K+ conductance (De Koninck and Henry, 1988, 1992). It has been reported that adenosine‐activated K+ channels in cardiac muscle cells are the ATP‐sensitive K+ channels (Kirsch et al., 1990). Therefore, we questioned whether these channels might mediate the purinergic IPSP we have observed in nociceptive dorsal horn neurones. We report here that glibenclamide, a blocker of ATP‐sensitive K+ channels (Ashcroft, 1988; Schmid Antomarchi et al., 1987a, b), blocks the inhibition of nociceptive neurones by vibratory stimulation when this compound is administered locally by iontophoresis or systemically by intravenous injection. In addition, direct intracellular injection of ATP was found to block the IPSP evoked by vibratory stimulation. These data indicate that the purinergic IPSP in nociceptive spinal neurones is mediated via ATP‐sensitive K+ channels. As inhibition of nociceptive dorsal horn neurones may be the physiological basis for the analgesia produced by vibratory stimulation in humans (Bini et al., 1984; Lundeberg, 1984; Lundeberg et al., 1984; Ottoson et al., 1981), we propose that activation of ATP‐sensitive K+ channels in these neurones may mediate the analgesia produced by vibration. © Wiley‐Liss, Inc.