bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative analysis of the effects of iontophoretically applied dopamine in different regions of the rat brain, with special reference to the cingulate cortex
Authors: Beauregard Mario , Ferron André , Descarries Laurent 
Published: December 2004

AbstractA systematic comparison of the effects of iontophoresed dopamine (DA) was carried out in the neostriatum (NS), nucleus accumbens (Acb) and anterior cingulate (ACg), prefrontal (PF) and parietal (Par) cortex of urethane‐anesthetized rats, before and after treatment with the specific DA uptake blockers GBR 12909 and Bupropion. Similar experiments were also conducted after DA denervation with 6‐hydroxydopamine and after DA depletion with α‐methyl‐p‐tyrosine. The average rate of spontaneous neuronal firing was comparable in all regions, except in the NS after DA depletion. A majority of the units were inhibited by DA in every region and condition tested. As assessed with the IT50 index, the responsiveness to DA was not markedly different between regions, indicating that the postsynaptic sensitivity to this amine is independent of the density of DA receptors and of DA innervation. In contrast, the average duration of DA inhibitions (RT90) was considerably longer (5‐fold) in the intact ACg than in the PF, Par, NS, or Acb. Moreover, treatment with both DA uptake blockers reduced the duration of DA inhibitions in ACg (4‐ to 9‐fold); while lengthening it in PF, NS and Acb; and having no apparent effect in Par. DA depletion and DA denervation also reduced the duration of the DA inhibitions in ACg without effect in Par. Taken together, these results provide further evidence for the existence of a presynaptic, positive‐feedback mechanism in ACg, triggered by DA, and favouring the further release of this transmitter upon its reuptake in DA nerve terminals.
Severe depletion of cocaine recognition sites associated with the dopamine transporter in Parkinson's‐diseased striatum
Authors: Kaufman Marc J. , Madras Bertha K. 
Published: December 2004

AbstractThe cocaine congener [3H]CFT, also designated [3H]WIN 35,428 (2β;‐carbomethoxy‐3β;‐(4‐fluorophenyltropane)), labels cocaine receptors associated with the dopamine transporter in primate striatum. Autoradiogrpahic distribution of [3H]CFT binding (5 nM) in human postmortem control and Parkinson's‐diseased striatal tissue sections was compared. In control tissue, high and comparable levels of [3H]CFT binding were observed in the putamen and caudate nucleus. At least 90–99% of total [3H]CFT bound was inhibited by (—)‐cocaine (30 μM), suggesting that a high proportion of [3H]CFT is specifically bound. In Parkinson's‐diseased tissue, binding sites for [3H]CFT were reduced by 80% in the caudate nucleus and 96% in the putamen. This pattern of depletion parallels the previously reported loss of dopamine in these brain regions (Kish, Shannak, and Hornykiewicz, New Engl. J. Med., 318:876–880, 1988). In the dorsal caudate nucleus of Parkinson's‐diseased tissue, a lateral‐to‐medial gradient of [3H]CFT binding was observed, with the lateral caudate more severely depleted than the medial caudate. The marked decrease of [3H]CFT binding sites in Parkinson's diseased striatum supports the following conclusions: (1) the dopamine transporter is localized primarily on presynaptic nigrostriatal terminals; (2) in the caudate and putamen, cocaine recognition sites are associated primarily with the dopamine transporter; (3) the low level of nonspecific binding of [3H]CFT and the marked depletion of [3H]CFT‐labeled sites suggest that radiolabeled derivatives of CFT or its congeners may be suitable imaging probes for presynaptic dopamine nerve terminals.
Distribution of somatostatin‐immunoreactive cell bodies and fibers in the neocortex of Macaca fuscata
Authors: Iritani Shuji , Satoh Keiji 
Published: December 2004

AbstractThe distribution of somatostatin‐immunoreactive cell bodies and processes was studied in the cerebral cortex of the macaque monkey (Macaca fuscata), by applying an immunohistochemical technique with a monoclonal antibody raised against somatostatin tetradecapeptide. Many somatostatin‐immunoreactive cell bodies and processes were observed in all regions of the cerebral cortex, i.e., frontal, parietal, temporal, insular, occipital, and cingulate cortices, and also in the underlying white matter. Three types of somatostatin‐contaning cell bodies were distinguished in the cerebral cortex. These cell bodies were distributed in layers II to VI of the cortex, and also in the underlying white matter. There were dense deposits of somatostatin‐containing granular structure in layers I and II, and many somatostatin‐containing processes in layers IV and V. The present observations demonstrate that in the primate neocortex somatostatin 14‐containing neuronal systems are as highly developed as other prosomatostatin‐derived peptides but differe from the latter systems in terms of cell morphology and fiber distribution.
Basal extracellular dopamine is decreased in the rat nucleus accumbens during abstinence from chronic cocaine
Authors: Parsons L. H. , Smith A. D. , Justice J. B. 
Published: December 2004

AbstractRats were treated for 10 days with cocaine (20 mg/kg, i.p.) followed by either 1 or 10 days of abstinence. On the test day a microdialysis method was performed in which dopamine (DA) was added to the perfusate at concentrations above and below the expected extracellular concentration (0, 2.5, 5, and 10 nM) to generate a series of points that can be interpolated to determine the concentration of no net flux, which represents the extracellular DA concentration. The slope of the line generated by this method is the in vivo recovery of the dialysis probe. After 1 day of abstinence, there was no significant difference in basal DA levels in the nucleus accumbens (N ACC) between cocaine treated (4.1 ± 0.3 nM; mean ± SEM) and saline‐treated (3.9 ± 0.2 nM) groups. However, there was a significant increase in the slope of the cocaine‐treated group (0.91 ± 0.04 vs. 0.67 ± 0.08; P >0.03). After 10 days of abstinence, there were reduced basal extracellular levels of DA in the N ACC of the cocaine‐treated group as compared with saline‐treated controls (P <0.002). The basal extracellular DA concentration in the N ACC was 2.1 ± 0.3 nM for the cocaine group and 3.9 ± 0.2 nM for the control group. The slopes of the curves were not significantly different for the cocaine (0.63 ± 0.07) and saline (0.64 ± 0.09) groups. There was a significant interaction between cocaine and the length of abstinence with respect to the reduction in basal extracellular DA in the N ACC (P <0.0008) and also an interaction between cocaine and the length of abstinence with respect to the slope of the regression lines (P <0.03). The results suggest that both basal levels and the dynamics of extracellular DA in the N ACC are altered by chronic cocaine. These alterations may have relevance to the dopamine depletion hypothesis of cocaine addiction.
Characterization of the distribution of Gαo in rat striatal synaptosomes and its colocalization with tyrosine hydroxylase
Authors: Wolf Marina E. , Granneman James G. , Kapatos Gregory 
Published: December 2004

AbstractDopaminergic striatal synaptosomes can be detected and isolated with a fluorescence‐activated cell sorter (FACS). In the present study, two antigens were detected simultaneously with primary antisera raised in different species and species‐specific fluorescent secondary antibodies with different emission spectra. Double‐label FACS analysis was used to determine whether tyrosine hydroxylase (TH) and the alpha subunit of Gαo (Gαo) are colocalized in striatal synaptosomes. Rabbit antibodies generated against a synthetic fragment of Gαo (corresponding to amino acids 22–35) combined with fluorescein‐conjugated secondary antibodies were used to detect Gαo‐containing striatal synaptosomes. Preadsorption of Gαo antiserum with the synthetic peptide antigen reduced labeling to the level obtained with preimmune serum. Approximately 65–75% of striatal synaptosomes were specifically labeled by Gαo antiserum. Tyrosine hydroxylase‐containing synaptosomes were detected with a mouse monoclonal antibody to TH and R‐phycoerythrin‐conjugated secondary antibody. They comprised 15–17% of total striatal synaptosomes. Double‐label studies indicated that at least 50% of TH‐containing synaptosomes also contained Gαo. These finding suggest that Gαo may not be a protein component of all striatal nerve terminals, and provide a basis for a role for Gαo in signal transduction within subpopulations of intrinsic and afferent nerve terminals, including those of nigrostriatal dopamine neurons.
Dissociative anesthesia and striatal neuronal electrophysiology
Authors: Kelland Mark D. , Chiodo Louis A. , Freeman Arthur S. 
Published: December 2004

AbstractCompared with results obtained in locally anesthetized, paralyzed rats, the dissociative anesthetic ketamine did not alter either the number of spontaneously active striatal neurons or the basal firing rate of striatal neurons; 90% of these cells exhibited the type I striatal neuron waveform. Chloral hydrate anesthesia suppressed both the occurrence and the firing rate of spontaneously active type I cells, but did not alter the activity of type II striatal neurons. Cortical stimulation preferentially activated type II cells in paralyzed rats and in chloral hydrate‐anesthetized rats. Thus, under dissociative anesthesia it is possible to study spontaneously active type I striatal neurons. However, a method of activation such as cortical stimulation is necessary to study type II striatal neurons.
Midbrain dopamine system electrophysiological functioning: A review and new hypothesis
Authors: Bunney Benjamin S. , Chiodo Louis A. , Grace Anthony A. 
Published: December 2004

AbstractThe pathogenesis of a variety of neurological and mental disorders has been attributed to the malfunctioning of central dopaminergic systems. Twenty years of investigation concerning the way that dopamine systems function in the brain has yielded a great deal of information about the control and behavior of these systems. This collection of seemingly disparate facts is reviewed. A hypothesis is then presented that attempts to synthesize from these facts a view of the electrophysiological functioning of midbrain dopamine systems that may be helpful in understanding brain mechanisms underlying the pathology of such disorders as Parkinson's disease and schizophrenia.
Chronic theophylline treatment increases adenosine A1, but not A2, receptor binding in the rat brain: An autoradiographic study
Authors: Lupica Carl R. , Berman Robert F. , Jarvis Michael F. 
Published: December 2004

AbstractChronic exposure to adenosine receptor antagonists results in an upregulation of brain adenosine A1 receptors as measured by traditional radioligand binding techniques. In the present study, quantitative receptor autoradiography was used to characterize alterations in rat brain adenosine A1 and A2 receptors following the repeated administration of high doses of theophylline. Daily administration of theophylline (75 or 100 mg/kg) markedly increased (125–150% of control) 1 nM [3H]cyclohexyladenosine binding to adenosine A1 receptors in specific cellular layers of the hippocampus, thalamus, and cerebellum with other brain regions showing more moderate increases in binding. By contrast, this chronic theophylline treatment did not produce any significant alterations in the binding of 4 nM [3H]CGS 21680 to adenosine A2 receptors, which were exclusively localized in the striatal region. This apparent differential sensitivity of adenosine receptor subtypes to chronic antagonist treatment suggests a possible intrinsic difference in the regulation of these receptor subtypes which may also be specific to particular brain regions. These results are discussed in relationship to other recent observations, indicating that the pattern of agonist binding to adenosine receptors may be regulated by a differential extent of coupling between adenosine receptors and G‐binding proteins in different brain regions.
Immunohistochemical study of cholecystokinin peptide in rat spinal motoneurons
Authors: Cortés Roser , Åman Katarina , Arvidsson Ulf , Terenius Lars , Frey Peter , Rehfeld Jens F. , Walsh John H. , Hökfelt Tomas 
Published: December 2004

AbstractWith the aid of indirect immunofluorescence histochemistry and sequence specific antibodies a possible localization of cholecystokinin (CCK) peptide in spinal motoneurons has been analyzed. To increase peptide levels, the sciatic nerve was ligated, and the area around the ligation was studied 24 hours later. For comparison, antisera raised against calcitonin gene‐related peptide (CGRP) and substance P were employed.With CCK specific antisera (directed to the N‐terminal portion of CCK‐8 or the midportion of CCK‐33) accumulation of peptide‐like immunoreactivity (LI) was observed in large, dilated axonal swelling proximal to, but at some distance from, the ligature. Such accumulations were also observed with C‐terminally directed CCK antiserum, but in addition numerous axons of smaller diameter extending up to the ligation contained this type of immunoreactivity. The latter antiserum is thought to cross‐react with CGRP. In fact, this staining pattern was indistinguishable from the one seen after incubation with CGRP antiserum. In contrast substance P‐LI could not be seen in the larger dilated axons but only in large numbers of thinner fibers close to the ligation. Double staining experiments revealed that the large dilations contained both CGRP‐ and CCK‐specific LI. Distal to the ligation CGRP‐ and substance P‐ but no specific CCK‐LI could be observed.The present findings support the view that CCK mRNA in spinal motoneurons is translated into CCK peptide, at least after axotomy, and that the peptide is transported into the motoneuron axon. However, compared to CGRP the CCK levels are presumably low, and the functional role of CCK peptide in motoneurons remains to be established.
Response to novelty predicts the locomotor and nucleus accumbens dopamine response to cocaine
Authors: Hooks M. Stacy , Jones Graham H. , Smith Amanda D. , Neill Darryl B. , Justice Joseph B. 
Published: December 2004

AbstractThe relationship between a rat's locomotor response to a novel environment and its behavioral and dopaminergic responses to cocaine was examined. Subjects were divided into two groups based on their locomotor response to a novel environment. Subjects who had a novelty response above the median were classified as high responders (HR), while those with a novelty response below the median were classified as low responders (LR). Following administration of cocaine‐HC1 (0, 2.5, 5.0, 10.0, or 15.0 mg/kg), HR rats showed a greater locomotor response than LR rats. Moreover, there was a significant correlation between a subject's locomotor response to the novel environment and the locomotor response to either 10.0 (r = 0.65) or 15.0 (r = 0.92) mg/kg cocaine. In a separate experiment, the extracellular concentration of dopamine in the nucleus accumbens (NACC) was monitored using microdialysis procedures. Following cocaine administration (15.0 mg/kg) HR rats showed a larger NACC dopamine response and greater locomotor activity than LR rats. In addition, there was a threefold greater locomotor activity to dopamine ratio in HR rats than in LR rats. A correlation between a subject's locomotor response to a novel environment and the dopaminergic response to cocaine was also evident. These results suggest that differences in the locomotor response to cocaine can, to some degree, be predicted by a rat's locomotor response to a novel environment, and that variations in dopamine‐dependent mechanisms of the NACC may underlie these individual differences.
Expression of calmodulin‐dependent enzymes in developing rat striatum is not affected by perturbation of dopaminergic systems
Authors: Polli Joseph W. , Kincaid Randall L. , Torris John , Billingsley Melvin L. 
Published: December 2004

AbstractTranssynaptic regulation is one mechanism that controls expression of several calmodulin (CaM)‐dependent enzymes. This observation and the demonstration that expression of several CaM‐dependent enzymes in developing striatum occurred with a spatial and temporal pattern similar to that seen for dopamine and tyrosine hydroxylase suggested that the nigrostriatal pathway may influence the expression of CaM‐binding proteins (CaM‐BPs) during striatal development. Therefore, the possible role of nigrostriatal dopamine systems regulating the expression of CaM‐dependent enzymes was studied in Sprague‐Dawley rats by using surgical hemitransections of brain, 6‐hydroxydopamine lesions, and chronic haloperidol treatments. Alterations in CaM‐BP expression following perturbation of the developing nigrostriatal tract were analyzed by using immunoblots, biotinylated CaM overlays, and enzyme assays. The extent of nigrostriatal lesions was assessed by using depletion of immunoreactive tyrosine hydroxylase levels in striatum. All there experimental paradigms failed to alter the normal developmental expression of CaM‐dependent enzymes. From these results we conclude that the increased expression of CaM‐dependent enzymes during striatal development is not directly dependent on synaptic input from the nigrostriatal dopamine system.
Effects of neurotensin on midbrain dopamine neurons: Are they mediated by formation of a neurotensin—dopamine complex?
Authors: Shi Wei‐Xing , Bunney Benjamin S. 
Published: December 2004

AbstractThe effects of neurotensin on midbrain dopamine neuron activity were studied in brain slices using single‐unit recording techniques. At low concentrations (0.2–10 nM), neurotensin attenuated dopamine‐induced inhibition without a significant effect on the basal firing rate. At higher concentrations (>10 nM), however, it consistently caused an increase in cell activity. At even higher concentrations (>100 nM), a sudden cessation of cell activity preceded by an increase in firing rate was observed. Whether this effect of neurotensin was due to depolarization inactivation or to a toxic effect of the peptide at high concentrations remains to be determined.To determine whether the effects of neurotensin were mediated by formation of a neurotensin—dopamine complex, several neurotensin analogues were studied. Neurotensin (8–13), which binds to both neurotensin receptors and dopamine, mimicked the effects of native neurotensin. Neuromedin N, which competes with neurotensin for the same receptor but does not bind to dopamine, also mimicked the effects. However, neurotensin (1–11), which forms a complex with dopamine but is inactive in competing for neurotensin receptors, was ineffective. In addition, the excitatory effect of neurotensin was not attenuated in the presence of dopamine receptor blockade by sulpiride. These results suggest that formation of a neurotensin–dopamine complex may not account for the action of neurotensin on dopamine cells. When combined with the fact that there is a high density of neurotensin receptors on dopamine cells, our results support the suggestion that the observed effects of neurotensin on dopamine neurons are most likely mediated by an activation of neurotensin receptors.
Distribution of cocaine recognition sites in monkey brain: I. In vitro autoradiography with [3H]CFT
Authors: Kaufman Marc J. , Spealman Roger D. , Madras Bertha K. 
Published: December 2004

AbstractThe cocaine analog [3H]CFT ([3H]WIN 35,428) was used to map and characterize cocaine recognition sites in the squirrel monkey brain by quantitative autoradiography. Coronal tissue sections were incubated with 5 nM [3H]CFT to measure total binding or with [3H]CFT in the presence of 30 μM (−)‐cocaine to measure nonspecific binding. High densities of [3H]CFT binding sites were present in dopamine‐rich brain regions, including the caudate nucleus, putamen, nucleus accumbens, and olfactory tubercle. In each of these regions specific binding was greater than 90% of total binding. Several additional brain regions exhibited intermediate densities of [3H]CFT binding, including the substantia nigra, the zona incerta, the amygdala, and the hypothalamus. Low, though measurable levels of binding were observed in the bed nucleus of the stria terminalis, the ventral tegmental area, the medial preoptic area, the pineal, the hippocampus, and thalamic central nuclei. Near‐background levels of binding were found in white matter, cortical regions, globus pallidus, and cerebellum. The pharmacological specificity of [3H]CFT binding in various brain regions was determined in competition studies using [3H]CFT and a range of concentrations of selected monoamine uptake inhibitors. In all brain regions examined, stereoselective inhibition of [3H]CFT binding was observed for the (−) over the (+) isomer of cocaine. For other drugs tested, competition experiments indicated a rank order of potency of GBR 12909 ≥ CFT ≥ bupropion, suggestive of binding of [3H]CFT to elements of the dopamine transport system. The results demonstrate that although densities of [3H]CFT binding sites are highest in the caudate nucleus, putamen, and nucleus accumbens/olfactory tubercle, significant levels of binding can be detected in other brain regions that may contribute to the behavioral and physiological effects of cocaine.
Effects of endogenous dopamine on kinetics of [3H]N‐methylspiperone and [3H]raclopride binding in the rat brain
Authors: Trevor Young L. , Wong Dean F. , Goldman Serge , Minkin Elynne , Chen Catherine , Matsumura Kaname , Scheffel Ursula , Wagner Henry N. 
Published: December 2004

AbstractCompetition by endogenous dopamine with the binding of D2 dopamine receptor ligands may be important in the interpretation of positron emission tomography (PET) neuroreceptor studies. PET studies with N‐methylspiperone (NMSP) have revealed increased D2 dopamine receptors in schizophrenia, whereas studies with raclopride (RAC) have not detected such differences. This may be due, at least in part, to differences in competition with endogenous dopamine for ligand binding. To determine effects of endogenous dopamine on in vivo receptor binding, adult male rats were preinjected with amphetamine and reserpine prior to [3H]NMSP or [3H]RAC. Striatal to cerebellar ratios of ligand binding were determined. To approximate the conditions of a PET study, a kinetic model was employed to examine effects of pharmacologically increasing brain dopamine levels (amphetamine pretreatment) on PET ligand binding. In these experiments, tail veins and arteries were cannulated and kinetic parameters determined from normalized integral plots in rats treated with amphetamine prior to radioligand injection. Both [3H]NMSP (43.5%) and [3H]RAC (41.5%) binding were significantly decreased after amphetamine pretreatment, whereas after reserpine pretreatment [3H]RAC binding was increased (52.7%). Kinetic studies revealed a marked resistance of [3]NMSP to competition with endogenous dopamine released by amphetamine. In contrast, kinetic parameters of [3H]RAC were markedly reduced at all time intervals. This suggests significant differences in competition with endogenous dopamine by [3H]NMSP and [3H]RAC, determined kinetically. These findings may have important implications for the interpretation of PET neuroreceptor studies.