bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of striatal [11C]cocaine binding to decreases in synaptic dopamine
Authors: Gatley S. John , Volkow Nora D. , Fowler Joanna S. , Dewey Stephen L. , Logan Jean 
Published: December 2004

AbstractWe have previously shown that tracer concentrations of [11C]cocaine binding to the dopamine transporter (DAT) in human and baboon striatum can be visualized using positron emission tomography (PET). To determine whether the concentration of dopamine normally present in the synaptic cleft can compete with [11C]cocaine for transporter binding sites, we conducted baboon PET studies with drugs (sodium 4‐hydroxybutyrate, four studies, 200 mg/kg gamma‐vinylGABA, three studies, 300 mg/kg and citalopram, three studies, 2 mgkg) expected to decrease synaptic dopamine. Each study involved two [11C]cocaine injections and PET scans separated by 2‐4 h, with drug administration after the first injection, and without movement of the subject between scans. Time‐activity data from striatum and from cerebellum were used with the arterial plasma input function to determine graphically by Logan plotting [11C]cocaine distribution volumes for the brain regions. Specific binding of [11C]cocaine to DAT in striatum was calculated as the distribution volume ratio (DVR) for striatum and cerebellum. In nine of the ten studies drug treatment produced a small increase in DVR (range, 1‐ll%), and in seven of these studies the increase was >7%. The mean increase was 6.2 ± 4.1%. The reproducibility of the DVR measure was assessed by comparing [11C]cocaine studies conducted without pharmacological treatments using individual baboons on separate days, and thus involving possible repositioning errors, as well as long‐term changes in the state of the striatal dopamine system. For four individual baboons with three or four studies per animal the mean (±s.d.) values of DVR were 1.73 ± 0.03, 1.39 ± 0.03, 1.53 ± 0.06, and 1.54 ± 0.12. The maximum differences between baseline DVRs, expressed as percentage of the lowest value, were 5%, 5%, 9%, and 20%. For two other baboons with two studies each, the between study differences were 1% and 9%. Thus within‐subject variability was quite low, even with repositioning. The results suggest that [11C]cocaine binding to the DAT is sensitive to pharmacological alterations in the concentration of synaptic dopamine. However, the sensitivity of [11C]cocaine to dopamine‐depletion is less than that of the D2 receptor radioligand [11C]raclopride, in agreement with literature in vitro binding studies, and is unlikely to be a serious issue in PET evaluations of DAT density. © 1995 Wiley‐Liss, Inc.
Distribution of GABAAreceptor alpha 1 subunit‐like immunoreactivity in comparision with that of enkephalin and substance P in the rat forebrain
Authors: Marksteiner J. , Lassnig E. , Humpel C. , Sieghart W. , Kaufmann W. , Saria A. 
Published: December 2004

AbstractThe γ‐aminobutyric acid‐A receptor consists of several subunits. In this immunohistochemical study we investigated the regional distribution of the α1 subunit with an antibody directed against a specific amino acid sequence (1‐9) of the α1 subunit. We compared the distribution pattern of the α1 subunit‐like immunoreactivity with that of substance P‐ and enkephalin‐like immunoreactivities in adjacent sections of the rat forebrain. α1 subunit‐like immunoreactivity appeared in the form of varicosities and fibers. A band‐like terminal staining pattern (woolly fibers) that has been shown by others for substance P‐ and enkephalin‐like immunoreactivity is also observed for α1 subunit‐like immunoreactivity. In contrast to substance P and enkephalin, numerous α1 subunit‐like immunoreactive perikarya were found. The highest density of α1 subunit‐like immunoreactive fibers and perikarya was found in the pallidal areas and the substantia nigra pars reticulata whereas the nucleus accumbens and the caudate putamen displayed a low density. α1 subunit‐like immunoreactive neurons resembled typical pallidal neurons. Some of these neurons were pericellularly stained with enkephalin‐like immunoreactive varicosities in the dorsal pallidum.The distribution pattern of α1 subunit‐like immunoreactivity reflects a partial overlap with the substance P and enkephalin system although a differential distribution to each of these peptides was observed for cell bodies, fibers, and axon terminals. © 1995 Wiley‐Liss, Inc.
Effects of local connectivity on striatal function: Simulation and analysis of a model
Authors: Wickens J. R. , Kotter R. , Alexander M. E. 
Published: December 2004

AbstractNeuronal population activity was investigated by computer simulation of a network model based on the neostriatum. Three network topologies were studied, based on different assumptions about the synaptic connectivity among medium spiny neurons. In all networks neurons were interconnected by inhibitory synapses. The connectivity was either symmetric, in which case all connections between cells were reciprocal and equal in strength; or asymmetric. Simulations showed that networks with symmetric connectivity receiving randomly distributed afferent excitation produced stationary spatial activity patterns. In contrast, asymmetric connectivity in homogeneous networks produced slow travelling‐wave activity across the network. We suggest that the shape of the medium spiny neurons is an important determinant of synaptic connectivity and that changes in the shape of these neurons caused by Huntington's disease would result in asymmetric connectivity. Slow travelling‐wave activity produced by asymmetric connectivity in the neostriatum could explain some aspects of the choreic movement and some electromyographic features seen in Huntington's patients. © 1995 Wiley‐Liss, Inc.
IPT: A novel iodinated ligand for the CNS dopamine transporter
Authors: Kung Mei‐Ping , Essman William D. , Frederick Dana , Meegalla Sanath , Goodman Mark , Mu Mu , Lucki Irwin , Kung Hank F. 
Published: December 2004

AbstractAn iodinated cocaine derivative, N‐(3′‐iodopropen‐2′‐yl)‐2β‐carbomethoxy‐3β‐(4‐chlorophenyl)tropane (IPT), was evaluated as a probe for in vitro and in vivo labeling of dopamine (DA) and serotonin (5‐HT) transporters in Sprague‐Dawley rat brain. Saturation analysis of [125I]IPT in rat striatal homogenates, in two different buffer solutions, Tris‐HCl and phosphate, demonstrated a one‐site binding with affinities (Kd) of 0.25 ± 0.02 and 0.16 ± 0.02 nM and densities (Bmax) of 939 ± 161 and 1,982 ± 137 fmol/mg protein, respectively. Competition by known DA transporter ligands showed a rank order of RTI‐55 > IPT > GBR12909 > mazindol > (−)cocaine. Binding to 5‐HT transporter sites was evaluated in rat cortical homogenates. Saturation experiment results showed a single site with a Kd value of 1.2 ± 0.2 nM and a Bmax value of 100 ± 20 fmol/mg protein. The rank order of potency of several monoamine uptake inhibitors (paroxetine > fluoxetine > mazindol > R‐nisoxetine > GBR12909) suggests that [l25I] IPT labels 5‐HT transporters in rat cortical homogenates. Both ex vivo and in vitro autoradiographic studies revealed high densities of [125I]IPT binding sites in the caudate nucleus, putamen, olfactory tubercle and nucleus accumbens, areas known to be rich in dopaminergic innervation. Moderate accumulation of activity was also observed in the substantia nigra. The dorsal raphe, a region with a high density of 5‐HT innervation, was labeled using in vitro autoradiography with [125I]IPT, but the labeling using ex vivo autoradiography was less prominent at 30 min postinjection and not noticeable at 60 min postinjection. Furthermore, systemic administration of IPT to rats increased the locomotor activity, a behavioral effect consistent with the in vitro and in vivo characteristics of compounds acting at dopaminergic sites. These results demonstrate that [125I]IPT is a useful ligand for in vitro labeling of DA and 5‐HT transporters and a ligand selective for labeling of DA transport sites in vivo. When labeled with I‐123,[123I]IPT holds promise as a SPECT imaging agent for studies of neuropsychiatric disorders that involve DA transporters. © 1995 Wiley‐Liss, Inc.
D3 and D2 dopamine receptors: Visualization of cellular expression patterns in motor and limbic structures
Authors: Larson Eric R. , Ariano Marjorie A. 
Published: December 2004

AbstractThe distribution of the D3 and D2 dopamine receptor subtypes in forebrain regions of the basal ganglia and mesocorticolimbic system was determined. This was assessed through combined fluorescent visualization of subtype selective anti‐peptide antibodies for these cloned receptors and detection of their ligand recognition sites using the D2 subfamily antagonist, N‐(p‐aminophenethyl) spiperone (NAPS fluoroprobe). The double‐labeling technique enabled direct comparison of the cloned receptor proteins and NAPS fluoroprobe binding in vitro. The application of these two methods together produced results comparable to single‐labeling paradigms. Functional D3 receptors, defined as the coincident fluorescence of the D3 receptor antisera and fluoroprobe binding, were detected in the core region of the nucleus accumbens and exhibited a laminated expression pattern in the frontal cortex. D3 receptor protein was expressed robustly in neurons of the dorsolateral striatum, but showed an intense neuropil reaction in the globus pallidus. Functional D2 receptors, defined as the coincident fluorescence of the D2 receptor antisera and fluoroprobe binding, were detected in the frontal cortex and the medial shell of the nucleus accumbens. Thus, heterogeneities occurred in the cellular expression of functional D3 and D2 receptors in forebrain dopaminoceptive areas. D3 appears more related to basal ganglia and structures involved with motoric behavior, while D2 was associated with regions associated with cognitive/affective functions. © 1995 Wiley‐Liss, Inc.
The road to tranquility: The search for selective anti‐anxiety agents
Authors: Estes J. Worth 
Published: December 2004

AbstractThe earliest treatments of anxiety included cathartics and emetics, which were used to remove the excess of black bile (hence our word melancholia) thought to be responsible for the patient's demeanor. By the 1700s, physicians were prescribing drugs that are more selective for the CNS, chiefly opium and strengthening tonics. In the 1860s cardioactive drugs such as atropine, aconite, and digitalis were assumed to counteract anxiety because it could be associated with tachycardia andlor melancholia. A little later, the emergence of laboratory animal models, culminating in the conditioned avoidance response, and also Freudian psychiatry, permitted the evolution of new definitions of anxiety, as well as the introduction of sedative agents such as KBr, chloral hydrate, and barbiturates for its treatment. The first somewhat selective anxiolytics, reserpine, meprobamate, and chlorpromazine, appe ared in the early 1950s, while in 1959 the benzodiazepines were the first to prove more selective than all the others in a systematic battery of screening tests. © 1995 Wiley‐Liss, Inc.
In vivo‐synthesized radioactively labelled α‐methyl serotonin as a selective tracer for visualization of brain serotonin neurons
Authors: Cohen Z. , Tsuiki K. , Takada A. , Beaudet A. , Ddiksic M. , Hamel E. 
Published: December 2004

AbstractTo investigate the use of α‐[3H]methyl tryptophan (α‐[3H]MTrp) as a tracer for the in vivo study of brain serotonergic neurons, we examined whether α‐[3H]MTrp and its metabolite α‐[3H]methyl serotonin (α‐[3H]M5‐HT) selectively label serotonergic neurons and whether once accumulated in these neurons, the radioactive metabolite behaves like endogenous serotonin. Rats received a systemic injection of 1–5 mCi of α‐[3H]MTrp and 24 h later their brains were immediately removed or fixed by perfusion before removal. Tissue sections in which serotonergic neurons had been immunostained for 5‐HT or its synthesizing enzyme, tryptophan hydroxylase, were processed for radioautography at the light and electron microscopic level. In another group of rats, the release of radioactivity from different brain areas was studied both under basal and depolarizing conditions. In the dorsal raphe nucleus, the light microscopic examination revealed almost complete colocalization between serotonergic neurons and those that accumulated radioactivity, with a heterogeneity in the content of α‐[3H]M5‐HT among the various cells. At the ultrastructural level, immunoidentified serotonergic perikarya and dendritic processes in the dorsal raphe nucleus, as well as nerve terminals in the cerebral cortex were also found to contain α‐[3H]M5‐HT. Under basal conditions, radioactivity was released from the brainstem raphe region and from projection areas such as the striatum and hippocampus. The basal output of α‐[3H]M5‐HT increased approximately twofold after a depolarizing 50 mM KCl solution was added to the perfusion fluid. These findings suggest that newly synthesized α‐[3H]M5‐HT can be released both at somatodendritic and terminal sites. In sum, the present results demonstrate the selectivity of α‐[3H]MTrp as a tracer for serotonergic cells, and further suggest that α‐[3H]MTrp radiolabelling provides for a direct assessment of the in vivo dynamics of brain serotonergic neurons at the cellular level. © 1995 Wiley‐Liss, Inc.
Time‐course of modifications elicited by reserpine on the density and mRNA synthesis of the vesicular monoamine transporter, and on the density of the membrane dopamine uptake complex
Authors: Naudon L. , Leroux‐Nicollet I. , Raisman‐Vozari R. , Botton D. , Costentin J. 
Published: December 2004

AbstractThe long‐term effects of a unique injection of reserpine (5 mg/kg s.c.) on the vesicular monoamine transporter and dopamine uptake complex have been investigated, in parallel with behavioral and neurochemical effects. Early after treatment, a dramatic decrease in locomotor activity, as well as a marked depletion in striatal dopamine (DA), associated with a prominent enhancement in dopaminergic turnover were observed in reserpine‐treated rats. From 2 to 60 days after reserpine injection, a recovery in locomotor activity occurred, in parallel with an increased DA content in the striatum, reaching about 50% of controls at day 60. At this time, the dopamine turnover was quite normal. The density of the dopamine uptake sites in the striatum, studied with 3H GBR12783, was unchanged after reserpine treatment at any time studied up to 60 days. By contrast, the density of binding sites for 3H dihydrotetrabenazine (3H TBZOH), a marker for the vesicular monoamine transporter, remained dramatically decreased in the striatum all over the time of the study (> −90% of controls at day 2 and −80% at day 30 and 60). A lesser decrease (−60%) was observed in the substantia nigra pars compacta (SNc), 2 and 30 days after reserpine treatment. This suggests that at least 60% of the vesicular monoamine transporter is sensitive to reserpine in this cell bodies region, indicating that this proportion of the transporter is integrated in functional vesicles, a prerequisite for reserpine binding. On the other hand, in spite of profound modifications of DA levels and neuronal activity, induced by a persistent blockade of the vesicular uptake process, the density of mRNA encoding the vesicular monoamine transporter remained constant in the SNc from 2 to 60 days following reserpine injection. © 1995 Wiley‐Liss, Inc.
Subcellular localization of synaptophysin in noradrenergic nerve terminals: A biochemical and morphological study
Authors: Annaert Wim G. , Llona Isabel , De Ridder Erik , Weyns Andre , Quatacker Jos , De Potter Werner P. 
Published: December 2004

AbstractThe subcellular localization of synaptophysin was investigated in noradrenergic nerve terminals of bovine vas deferens and dog spleen and compared with membrane‐bound and soluble markers of noradrenergic storage vesicles. At the light microscopical level chromogranin A‐ and cytochrome b561‐ immunoreactivity revealed an identical and very dense innervation of the entire vas deferens. In the case of synaptophysin, most immunoreactivity was found only in the outmost varicosities closest to the lumen, which were also positive for chromogranin A. Small dense‐core vesicles of dog spleen were purified using a combination of velocity gradient centrifugation and size exclusion chromatography. Small dense‐core vesicles were enriched 64 times as measured by the noradrenaline content. Enrichments for dopamine‐β‐hydroxylase were in a similar range. Synaptophysin‐containing vesicles were smaller in size and they did not contain the typical noradrenergic markers dopamine‐β‐hydroxylase, cytochrome b561, and noradrenaline. Instead, they might store adenosine triphosphate (ATP). A greater part of synaptophysin immunoreactivity was consistently found at high sucrose densities at the position of large dense‐core vesicles. © 1995 Wiley‐Liss, Inc.We conclude that in the noradrenergic nerve terminal: (1) small dense‐core vesicles have a membrane composition similar to large dense‐core vesicles, indicating that the former are derived from the latter; and (2) synaptophysin seems not to be present on small dense‐core vesicles. We suggest the possibility that synaptophysin‐containing vesicles form a residual population whose role in neurotransmission has been taken over by large and small densecore vesicles following noradrenergic differentiation.
Plastic effect of soiled bedding on the structure of synapses in rat accessory olfactory bulb
Authors: Ichikawa Masumi , Matsuoka Masato , Mori Yuji 
Published: December 2004

AbstractThe effects of exposure to soiled bedding on synaptic morphology in the accessory olfactory bulb (AOB) were examined in adult male rats. Forty‐day‐old male rats were isolated. One group was exposed to bedding soiled by male and female rats (EC). Another group was exposed only to male‐soiled bedding (SC). A third group was exposed to clean bedding (IC). After 2 months, the animals were sacrificed for electron microscopy. The size and the numerical density of synapses were measured in the glomerulus and the granule cell layer. In the glomerulus, the mean size of the synapses was significantly greater in the EC than in the IC group, whereas that in the SC group appeared to be intermediate between those in the EC and the IC groups but was not significantly different from those in the EC and the IC groups. There was no statistically significant difference in the density of synapses among the three groups. Synapses in the granule cell layer are classified into two types: (1) perforated synapses, which are characterized by discontinuities in their postsynaptic thickenings, and (2) nonperforated synapses. The mean size of perforated synapses was significantly greater in the EC than in the IC and SC groups; however, no statistically significant difference was observed in the size of nonperforated synapses among the three groups. Moreover, no statistically significant difference was observed in the numerical densities of either perforated or nonperforated synapses among the three groups. These results suggested that exposure to a more complex soiled bedding environment (i.e., to bedding soiled by both male and female rats) can induce greater structural changes of the synapses in the AoB of male adult rats. © 1995 Wiley‐Liss, Inc.
Electrochemical evidence of increased dopamine transmission in prefkontal cortex and nucleus accumbens elicited by ventral tegmental μ‐opioid receptor activation in freely behaving rats
Authors: Noel Miriam Beth , Gratton Alain 
Published: December 2004

AbstractChronoamperometry was used in combination with monoamine‐selective electrodes to monitor, in nucleus accumbens (NAcc) and prefrontal cortex (PFC) of freely behaving rats, changes in dopamine (DA)‐like electrochemical signals elicited by unilateral ventral tegmental microinjections of the selective μ‐opioid receptor agonist D‐Ma, N‐Me‐Phe‐Gly‐01‐Enkephalin (DAMGO; 0.01, 0.1, and 1.0 nmol). The results show that DAMGO dose‐dependently increased electrochemical signals both in NAcc and PFC within a few minutes of injection. While DAMGO elicited signal increases of comparable amplitudes in both regions, the increases recorded in PFC were significantly longer lasting than those in NAcc; at the highest dose tested (1.0 nmol), DAMGO produced signal increases that lasted (mean ± sem) 129 ± 7.3 min in PFC and 96 ± 12.5 min in NAcc. Pretreatment with the opioid receptor antagonist, naloxone (2 mgkg, sc), significantly attenuated the peak amplitude and reduced the duration of DAMGO‐in‐ duced (0.1 nmol) signal increases both in PFC and NAcc. In contrast, pretreatment with apomorphine (50 μg/kg, sc), a D1/D2 DA receptor agonist, significantly reduced the duration and the rate of rise of the signal increases in both regions but had little effect on the peak increases in signal. Unilateral ventral tegmental DAMGO administration (0.01, 0.1, and 1.0 nmol) also caused dose‐dependent increases in contraversive circling the duration of which approximated that of the signal increases recorded in NAcc. However, differences in the time courses of DAMGO‐induced contraversive circling and signal increases in NAcc suggest that the behavioral stimulant effect of ventral tegmental μ‐opioid receptor activation may not be mediated exclusively by meso‐NAcc DA neurons. The results of this study suggest that enkephalins modulate the activity of meso‐PFC DA neurons and that behaviorally relevant activation of μ‐opioid receptors in the ventral tegmental area increases DA transmission in PFC to a same, if not to a greater extent as in NAcc. These findings are discussed in relation to evidence indicating that the response of meso‐NAcc DA neurons to a variety of stimuli, including drugs of abuse, is indirectly regulated by a DA‐sensitive neurons in PFC. © 1995 Wiley‐Liss, Inc.
Elevations of nucleus accumbens dopamine and DOPAC levels during intravenous heroin self‐administration
Authors: Wise Roy A. , Leone Paola , Rivest Robert , Leeb Kira 
Published: December 2004

AbstractExtracellular dopamine and DOPAC (3,4‐dihydroxyphenylacetic acid) levels in nucleus accumbens were sampled by microdialysis and quantified with high‐ performance liquid chromatography during intravenous heroin self‐administration sessions in rats. Dopamine levels in 10 and 20 min samples were elevated following the first injection of each session, reaching a plateau of elevation within the first two or three injections and falling back toward baseline only when drug access was terminated. Elevations were in the range of 150–300% when unit dosages of 0.05–0.2 mgkg were given. Increasing the work requirement from FR‐1 to FR‐10 did not appear to alter the degree of elevation of dopamine levels, and dopamine levels fell during extinction while lever‐pressing rates increased 20‐fold. While animals compensated for unit dose changes between 0.05 and 0.2 mg/kg/injection, adjusting their response rate such that the same hourly drug intake and the same asymptotic dopamine levels were maintained across these conditions, at 0.4 mg/kg/injection hourly drug intake and asymptotic dopamine levels were elevated beyond the levels sustained by the lower doses. These findings confirm that self‐administered doses of intravenous heroin are sufficient to activate the mesolimbic dopamine system and suggest that significant heroin “craving” can emerge when dopamine levels are still moderately elevated, long before the development of dopamine depletion associated with opiate withdrawal. © 1995 Wiley‐Liss, Inc.