bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor selectivity of cholecystokinin effects on mesoaccumbens dopamine neurons
Authors: Kelland Mark D. , Zhang Jing , Chiodo Louis A. , Freeman Arthur S. 
Published: December 2004

AbstractExtracellular recording techniques were combined with antidromic stimulation to examine the effects of C‐terminal cholecystokinin (CCK) fragments and CCK antagonists on the activity of identified mesoaccumbens dopamine (MADA) neurons in chloral hydrate‐anesthetized rats. These experiments were designed to determine the receptor selectivity of sulfated CCK octapeptide (CCK‐8S) effects on MADA cells. Neither CCK tetrapeptide (CCK‐4) nor unsulfated CCK octapeptide (CCK‐8U) significantly altered MADA cell basal firing rate or responsiveness to the inhibitory effects of the D2 DA agonist quinpirole. As reported previously for ventral tegmental area DA cells, CCK‐8S produced increases or decreases in the firing rate of most MADA cells sampled. CCK‐8S also enhanced the sensitivity of MADA neurons to quinpirole‐induced inhibition. This increase in sensitivity to quinpirole was blocked by pretreatment with the nonselective CCK receptor antagonist proglumide and the preferential CCK‐A receptor antagonist CR 1409 but not by the preferential CCK‐B receptor antagonist L‐365, 260. The inactivity of CCK‐4 and CCK‐8U in these tests and the results with the antagonists suggest that the effects of CCK‐8S on MADA neuronal activity are mediated by CCK‐A receptors.
Some pharmacological differences between hippocampal excitatory and inhibitory synapses in transmitter release: An in vitro study
Authors: Kamiya Haruyuki 
Published: December 2004

AbstractThe effects of adenosine, carbachol, and baclofen on synaptic transmission between neurons in cultured rat hippocampal explants were studied using the tight‐seal whole cell clamp technique. In the culture, stimulations of neurites cause postsynaptic currents (PSCs) in nearby neurons under voltage‐clamp condition. In the presence of 20 μM bicuculline, most PSCs were considered as glutamatergic excitatory postsynaptic currents (EPSCs), because they were blocked by glutamate antagonist, kynurenate at 1 mM. In the presence of 1 mM kynurenate, PSCs seemed to be inhibitory postsynaptic currents mediated by γ‐aminobutyric acid (GABA), because they were blocked by GABA antagonist, bicuculline at 20 μM. Adenosine at 100 μM and carbachol at 10 μM suppressed these EPSCs to about 35% of control. However, adenosine and carbachol at the same concentration did not suppress the IPSCs. Baclofen at 10 μM suppressed both EPSCs and IPSCs significantly (EPSCs: to about 40% of control, IPSCs: to about 30% of control). In contrast, membrane currents elicited by ionophoretically applied glutamate and GABA were not suppressed by 100 μM adenosine, 10 μM carbachol, and 10 μM baclofen. From these results, it is suggested that the pharmacological sensitivities of transmitter release from presynaptic terminals are different between glutamatergic excitatory synapses and GABAergic inhibitory synapses in hippocampal cultures.
Bi‐affinity α1‐adrenoceptor binding in normal rat brain in vivo
Authors: Gjedde Albert , Dyve Suzan , Yang Yu‐Jia , McHugh Michael , Pappius Hanna M. 
Published: December 2004

AbstractThe specific binding in rat brain in vivo of [125I]HEAT ([125I]iodo‐2‐[β;‐(4‐hydroxyphenyl)ethylamino methyl)], a selective α1‐adrenoceptor ligand, was analyzed by a method designed to distinguish sites with different affinities. The data indicate at least two sites with different affinities for the α1‐adrenoreceptor in normal rat brain in vivo: A high‐affinity site with Kd (half‐saturation constant) of 3.6 ± 0.7 nM (AV ± SD), and a low‐affinity site with Kd of 668 ± 552 nM. The density (Bmax) of the high‐affinity site in nine brain regions—auditory, visual, sensorimotor (four layers) and frontal cortex and lateral thalamic and medial geniculate nuclei—varied from 2.2 ± 0.8 to 14.6 ± 0.6 pmole/g, while the low‐affinity range was 149 ± 44 to 577 ± 30 pmole/g. The results also revealed a very dynamic relationship between the two sites regulated by the concentration of the ligand ranging from 80% preponderance of the high‐affinity sites at low ligand concentrations to more than 95% preponderance of the low‐affinity sites at high ligand concentrations.
[3H]Paroxetine binding and serotonin content of rat and rabbit cortical areas, hippocampus, neostriatum, ventral mesencephalic tegmentum, and midbrain raphe nuclei region
Authors: Dewar Karen M. , Reader Tomás A. , Grondin Louise , Descarries Laurent 
Published: December 2004

AbstractThe high‐affinity binding of [3H]paroxetine to membranes was measured in different regions of the rat and rabbit brain: cingulate, frontal, parietal, piriform, entorhinal, and visual cortical areas; dorsal and ventral hippocampus; rostral and caudal halves of neostriatum (rat) or caudate nucleus and putamen (rabbit); ventral mesencephalic tegmentum; and midbrain raphe nuclei region. The tissue concentrations of serotonin (5‐HT), 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) and 5‐hydroxy‐l‐tryptophan (5‐HTP) were also determined by high‐performance liquid chromatography (HPLC) in the same brain samples. The regional density of [3H]paroxetine binding varied in both species; the highest values (Bmax) were found in the midbrain raphe region and ventral mesencephalic tegmentum. The cortical values ranged from moderate to low, with a significantly higher density in the cingulate cortex of the rat compared with rabbit. In the rat, there was also a higher density in the ventral than dorsal hippocampus, and the caudal than rostral neostriatum. In the rabbit, the hippocampal and neostriatal values were generally lower and more uniform. In both species, there was an excellent correlation between regional 5‐HT levels and specific [3H]paroxetine binding (r = 0.87 in the rat and 0.96 in the rabbit). Considering the available quantitative data on the number of 5‐HT nerve cell bodies and axon terminals in different regions of the rat brain, it appears likely that the high amount of [3H]paroxetine binding in the midbrain raphe region and ventral mesencephalic tegmentum reflects the presence of 5‐HT uptake site on 5‐HT nerve cell bodies and dendrites as well as axon terminals. In other brain regions, the heterogenous distribution of [3H]paroxetine binding parallels that of the number of 5‐HT axon terminals, emphasizing the potential usefulness of this radioligand as a marker of 5‐HT innervation density.
Chronic cocaine administration and withdrawal of cocaine modify neurotensin binding in rat brain
Authors: Pilotte Nancy S. , Mitchell W. Mark , Sharpe Lawrence G. , De Souza Errol B. , Dax Elizabeth M. 
Published: December 2004

AbstractNeurotensin (NT) is a peptide colocalized with dopamine (DA) within some mesocorticolimbic DA neurons that are affected by cocaine. We assessed whether chronic treatment with cocaine and withdrawal from cocaine would alter NT binding within these and other areas in the brain. Rats were given infusions repeatedly of isotonic saline or cocaine (1 mg/kg i.v. every 12 min for 2 hr over 10 days) and then were killed within 15 min of the last treatment session (“cocaine” or “saline”) or 10 days later (“withdrawal”). Brains were processed for NT receptor autoradiography. Cocaine affected NT binding in the mesocortical regions differently from other areas. Within the mesocorticolimbic system, NT binding in the parabrachial pigmented nucleus of the ventral tegmental area (VTA) was 67% lower in cocaine‐treated rats killed immediately after or 10 days after their final infusion than in rats given saline. In contrast to the perikaryal region, significantly more NT binding occurred postsynaptically in the terminal areas of the VTA (prefrontal cortex [PFC] and substantia nigra, pars compacta) 10 days after withdrawal of cocaine than in the saline controls. NT binding in the nucleus accumbens was unaffected by cocaine or its withdrawal. Cocaine also decreased NT binding in non‐mesocorticolimbic areas, including the dorsal hypothalamic area and the zona incerta, but binding returned toward control levels 10 days after withdrawal from cocaine. These data suggest that in central areas poor in DA uptake sites such as the PFC, NT may be a critical element in the inactivation of DA. Chronic cocaine treatment and its withdrawal appear to uncouple the normal NT‐DA interaction at both the cell bodies and terminals. This may increase dopaminergic neurotransmission, a process that may be important to the development of behavioral sensitization.
Heterogeneous binding of [3H]4‐DAMP to muscarinic cholinergic sites in the rat brain: Evidence from membrane binding and autoradiographic studies
Authors: Araujo Dalia M. , Lapchak Paul A. , Quirion Remi 
Published: December 2004

AbstractThe present study shows that [3H]4‐DAMP binds specifically, saturably, and with high affinity to muscarinic receptor sites in the rat brain. In homogenates of hippocampus, cerebral cortex, striatum, and thalamus, [3H]4‐DAMP appears to bind two sub‐populations of muscarinic sites: one class of high‐affinity, low capacity sites (Kd < 1 nM; Bmax = 45–152 fmol/mg protein) and a second class of lower‐affinity, high capacity sites (Kd > 50 nM; Bmax = 263–929 fmol/mg protein). In cerebellar homogenates, the Bmax of [3H]4‐DAMP binding sites was 20 ± 2 and 141 ± 21 fmol/mg protein for the high‐ and the lower‐affinity site, respectively. The ligand selectivity profile for [3H]4‐DAMP binding to its sites was similar for both the high‐ and lower‐affinity sites; atropine = (—)QNB = 4‐DAMP » pirenzepine > AF‐DX 116, although pirenzepine was more potent (16‐fold) at the lower‐ than at the high‐affinity sites. The autoradiographic distribution of [3H]4‐DAMP sites revealed a discrete pattern of labeling in the rat brain, with the highest densities of [3H]4‐DAMP sites present in the CA1 sub‐field of Ammon's horn of the hippocampus, the dentate gyrus, the olfactory tubercle, the external plexiform layer of the olfactory bulb and layers I–II of the frontoparietal cortex. Although the distribution of [3H]pirenzepine sites was similar to that of [3H]4‐DAMP sites in many brain regions, significant distinctions were apparent. Thus, both the ligand selectivity pattern of [3H]4‐DAMP binding and the autoradiographic distribution of sites suggest that although the high‐affinity [3H]4‐DAMP sites may consist primarily of muscarinic‐M3 receptors, the lower‐affinity [3H]4‐DAMP sites may be composed of a large proportion of muscarinic‐M1 receptors.
Integrity of perforant path fibers and the frequency of action potential independent excitatory and inhibitory synaptic events in dentate gyrus granule cells
Authors: Staley Kevin J. , Mody Istvan 
Published: December 2004

AbstractWhole‐cell voltage clamp recordings in 400 μm thick hippocampal slices revealed discrete excitatory and inhibitory postsynaptic currents which persisted at synapses on granule cells following abolition of action potentials with 1 μM tetrodotoxin (TTX). The conductances associated with excitatory amino acid and GABAA receptor mediated events had mean peaks of 200 and 800 pS, and decayed monoexponentially with time constants of 5.6 and 5.3 ms. At a holding potential close to the normal resting membrane potential of granule cells (−80 to −90 mV), the frequency of glutamate/aspartate mediated spontaneous excitatory postsynaptic currents (sEPSCs) was decresed from 2.04 Hz in slices cut parallel to the plane of the perforant path to 0.87 Hz in slices cut in a plane that disrupted the distal perforant path fibres, suggesting that presynaptic integrity influences the rate of action potential independent neurotransmitter release. The orientation of the slicing had no effect on the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs).
Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories
Authors: Caldecott‐Hazard Sally , Morgan David G. , DeLeon‐Jones Frank , Overstreet David H. , Janowsky David 
Published: December 2004

AbstractThe present document is the second of three parts in a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various receptor/transmitter theories of depressive disorders are discussed in this section. Specifically, data supporting noradrenergic, serotonergic, cholinergic, dopaminergic, GABAergic and peptidergic theories, as well as interactions between noradrenergic and serotonergic, or cholinergic and catecholaminergic systems are presented. Problems with the data and future directions for research are also discussed. A previous publication, Part I of this review, dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders. A future publication, Part III of this review, discusses treatments for depression and some of the controversies in this field.
NMDA‐dependent heterosynaptic long‐term depression in the dentate gyrus of anaesthetized rats
Authors: Christie Brian R. , Abraham Wickliffe C. 
Published: December 2004

AbstractThis report examines the inductive mechanism involved in long‐term heterosynaptic depression (LTD) in the dentate gyrus of anaesthetized rats. Associative and non‐associative stimulus protocols were implemented, using the ipsilateral medial and lateral perforant path inputs to the dentate gyrus as the test pathways. In all experiments, the medial perforant path (MPP) received the conditioning stimuli which consisted of eight stimulus trains of 2 s duration, spaced 1 minute apart. Within each train the stimuli occurred as a burst of 5 pulses at 100 Hz, repeated at 200 ms intervals. The lateral perforant path (LPP) served as the test pathway in all of the initial experiments. In the associative condition, it received single pulses equally spaced between the medial path bursts. In the non‐associative condition, no lateral path stimuli were given during the medial path trains, In both condition, the application of the conditioning stimuli resulted in a long‐term potentiation (LTP) of the medial path evoked responses (P < 0.001), while the lateral path responses showed LTD (P < 0.001). A two‐way analyses of variance revealed there to be no difference between the two paradigms in the expression of LTP or LTD in naive pathways or in their ability to depress a potentiated pathway (P > 0.05) An occlusion test also showed there to be no further decreases in synaptic efficacy with the associative paradigm after the lateral path synapses were saturated with non‐associative LTD. The N‐methyl‐D‐aspartate (NMDA) receptor antagonist CPP (3‐((+)‐2‐carboxypiperazin‐4‐yl)‐propyl‐1‐phosphonic acid; 10 mg/kg) blocked the appearance of LTP and LTD in both conditions, and in fact, the lateral path responses in the associative condition actually showed a significant degree of enhancement (P < 0.001). This enhancement was also evidenced when the lateral path stimuli were administered alone without prior CPP administration (P < 0.05). The results imply that one set of common mechanisms is utilized in the induction of LTD in the dentate gyrus, whether the medial and lateral paths are activated in an associative or a non‐associative manner.
Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims
Authors: Biegon Anat , Fieldust Sheila 
Published: December 2004

AbstractAntibodies against tyrosine hydroxylase (TH, the rate‐limiting enzyme in norepinephrine synthesis) and dopamine β‐hydroxylase (DBH, the last enzyme in the synthesis) were used for immunohistochemical staining of human brain locus coeruleus sections, obtained postmortem form suicide victims and matched controls. Stain density over individual cells was quantified by a computerized, video‐camera‐based image analysis system. Mean stain density for TH was significantly lower (by about 30%) in the locus coeruleus of suicide victims. There was no difference between suicides and controls in DBH immunoreactivity or in the number of TH immunoreactive cells. Reduced TH availability, either genetically or environmentally determined, may contribute to the noradrenergic insufficiency postulated to occur in depression and the increased β‐adrenergic receptor concentrations observed in prefrontal cortex of suicide victims.
Amphetamine‐stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates
Authors: Innis Robert B. , Malison Robert T. , Al‐Tikriti Mohammed , Hoffer Paul B. , Sybirska Elzbieta H. , Seibyl John P. , Zoghbi Sami S. , Baldwin Ronald M. , Laruelle Marc , Smith Eileen O. , Charney Dennis S. , Heninger George , Elsworth John D. , Roth Robert H. 
Published: December 2004

AbstractWe used the reversibly binding D2 dopamine receptor radioligand [123I]IBZM (iodobenzamide) to test whether the endogenous neurotransmitter dopamine competes in vivo for radiotracer binding measured with single photon emission computed tomography (SPECT). In a series of nonhuman primate experiments (n = 27), the effects of temperature, amphetamine, haloperidol, and reserpine on brain uptake of [123I]IBZM were measured. Specific brain uptake of [123I]IBZM reached a peak by 100 min postinjection of radioligand and demonstrated a gradual, apparent “steady‐state” washout over the next 2 hr. Brain uptake was temperature dependent, with rates of washout of specifically bound radioligand greater under normothermic conditions (26%/hr: core body temperature 35–37°C) than under conditions of controlled hypothermia (11%/hr; 32–34°C). Given the greater retention of radioactivity, low‐temperature conditions were used in all other experiments. Administration of haloperidol (0.02 mg/kg IV) during the period of apparent steady state resulted in a dramatic increase in washout (60%/hr; p < 0.0001), consistent with its potent D2 receptor antagonist properties. d‐Amphetamine (1.0 mg/kg IV), which has negligible affinity for the D2 receptor but mediates the release of endogenous stores of dopamine, also enhanced washout (34%/hr; p < 0.0005). Reserpine pretreatment at doses (1.0 mg/kg) sufficient to cause greater than 90% depletion of striatal dopamine levels blocked this amphetamine‐enhanced washout (10%/hr; p < 0.05). Reserpine did not block the increased washout induced by the direct‐acting D2 receptor antagonist haloperidol. These results are consistent with the hypothesis that endogenous dopamine may effectively compete for radioligand binding in vivo in neuroreceptor imaging studies using PET and SPECT.
Repeated D1 dopamine receptor agonist administration prevents the development of both D1 and D2 striatal receptor supersensitivity following denervation
Authors: Hu Xiu‐Ti , White Francis J. 
Published: December 2004

AbstractFollowing 6‐hydroxydopamine (6‐OHDA) lesions of the nigrostriatal dopamine (DA) pathway, rat caudate‐putamen (CPu) neurons are supersensitive to the inhibitory effects of both D1 and D2 dopamine (DA) receptor selective agonists. In addition, both the necessity of D1 receptor stimulation for D2 agonist‐induced inhibition and the synergistic inhibitory effects of D1 and D2 agonists are abolished by denervation. The present study attempted to determine the relative roles of D1 and D2 DA receptors in the development of denervation supersensitivity to DA agonists and the “uncoupling” of functional interactions between the receptors following 6‐OHDA lesions of the nigrostriatal DA pathway. Beginning on the day after an intraventricular 6‐OHDA (or vehicle) injection, groups of rats received daily injections of either the selective D1 receptor agonist SKF 38393 (8.0 mg/kg, s.c.), the D2 agonist quinpirole (0.5 mg/kg, s.c.), or saline for 7 days. On the day following the last agonist injection, rats were anesthetized and prepared for extracellular single cell recording with iontophoretic drug administration. Daily administration of quinpirole selectively prevented the development of D2 receptor supersensitivity, whereas daily administration of SKF 38393 prevented the development of both D1 and D2 receptor supersensitivity. In addition, D1, but not D2, agonist treatment prevented the loss of synergistic inhibitory responses typically produced by 6‐OHDA lesions. Behavioral observations revealed similar effects; daily injections of SKF 38393, but not quinpirole, prevented contralateral rotational responses to the mixed D1/D2 agonist apomorphine (1.0 mg/kg, s.c.) in rats with unilateral 6‐OHDA lesions of the nigrostriatal pathway. After a 4‐week withdrawal from repeated D1 agonist treatment, both supersensitive inhibitory responses of CPu neurons and contralateral rotations to apomorphine were evident, indicating that the preventative effects on DA receptor supersensitivity were not permanent. These findings indicate that continued agonist occupation of striatal D1 DA receptors following DA denervation not only prevents the development of D1 DA receptor supersensitivity but also exerts a similar regulation of D2 receptor sensitivity.
Localization of drug reward mechanisms by intracranial injections
Authors: Wise Roy A. , Hoffman Diane C. 
Published: December 2004

AbstractIntracranial drug injections are useful in localizing brain areas where drugs of abuse initiate their habit‐forming actions. However, serious methodological problems accompany such studies. Pharmacological controls are necessary to assess non‐receptor‐mediated local actions of the drug, anatomical controls are necessary to rule out drug efflux to distal sites of action, and behavioral controls are necessary to separate rewarding from general activating effects of drugs. Five brain sites have been advanced as sites of rewarding opiate actions: the ventral tegmental area (VTA), nucleus accumbens septi (NAS), lateral hypothalamus, periaqueductal gray, and hippocampus. Current evidence appears to confirm two of these—VTA and NAS; evidence is currently incomplete in the case of the hippocampus and is conflicting in the case of the lateral hypothalamus and periaqueductal gray. Two sites have been advanced as sites of rewarding psychomotor stimulant actions: NAS and the frontal cortex; each site seems implicated, but puzzling differences between amphetamine and cocaine findings remain to be resolved. Each of the clearly implicated sites is local to dopamine cell bodies or dopamine terminals that have been implicated in the rewarding effects of brain stimulation, food, and sex.
Morphology and laminar distribution of neuropeptide Y immunoreactive neurons in the human striate cortex
Authors: Berman Nancy E. J. , Fredrickson Eric 
Published: December 2004

AbstractThe morphology, laminar distribution, and distribution relative to cytochrome oxidase patches of neuropeptide‐Y immunoreactive (NPY‐ir) neurons were studied in the human striate cortex. The density of NPY‐ir cells was highest in the white matter. NPY‐ir neurons were sparsely distributed within the cortical layers. NPY‐ir neurons were located in both cytochrome oxidase dense patch and interpatch regions. However, the paucity of NPY‐ir neurons in layer III, where cytochrome oxidase patches are most clearly demonstrated, precluded establishing a clear relationship of NPY‐ir neurons to cytochrome oxidase patches. NPY‐ir neurons exhibited a variety of nonpyramidal morphologies, and many of them had axons with recurrent or looped trajectories. A dense plexus of NPY‐ir axons was located just beneath the pia, and these axons were concentrated at the entry points of pial blood vessels. Other NPY‐ir neurons had cell bodies or processes in close proximity to cerebral capillaries. These results suggest a role of NPY in cortical metabolism, control of cerebral circulation, or activity‐related changes in local blood flow. © 1992 Wiley‐Liss, Inc.