bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine agonists at repeated “autoreceptor‐selective” doses: Effects upon the sensitivity of A10 dopamine autoreceptors
Authors: Jeziorski Michael , White Francis J. 
Published: January 2005

AbstractPrevious reports have established the ability of dopamine (DA) agonists to stimulate inhibitory DA autoreceptors at doses which minimally stimulate postsynaptic DA receptors, suggesting that hyperactive DA transmission may be controlled clinically by treatment with DA agonists. Little is known, however, about the possible loss of autoreceptor sensitivity that may occur after repeated treatment with low doses of DA agonists. Extracellular single cell recording and microinotophoretic techniques were used to measure the sensitivity of impulse‐regulating DA autoreceptors on A10 DA cells in the ventral tegmental area (VTA) of chloral hydrate‐anesthetized rats pretreated for seven days with repeated subcutaneous (s.c.) doses of the DA agonist apomorphine (APO). The ability of intravenous (i.v.) administration of the potent D2 DA agonist quinpirole (QUIN) to inhibit the firing of A10 cells was not attenuated in rats pretreated with repeated low doses (2 X 50 μg/kg/day, s.c.) of APO for 7 days, although higher doses (2 X 250 or 500 μg/kg/day) did cause subsensitive responses to QUIN. In rats pretreated with repeated low doses of APO, microiontophoretic application of DA on A10 cells revealed somewhat subsensitive responses. However, ibotenic acid lesions of postsynaptic cells in the nucleus accumbens (NAc) prior to initiation of APO treatment (2 X 50 μg/kg/day) did not alter the response of A10 cells to systemic QUIN, contradicting the possibility that the feedback projection from the NAc to the VTA was compensating for autoreceptor downregulation during systemic challenge with QUIN. In contrast, administration of the irreversible DA antagonist EEDQ (2 mg/kg, i.p.) to control and APO‐treated rats (2 X 50 μg/kg/day) 24 hr prior to recording did reveal a difference in A10 cell sensitivity to systemic QUIN and to microiontophoretic DA between the two groups, suggesting that “spare” DA autoreceptors may have concealed the down‐regulation of autoreceptors induced by repeated low doses of APO. Challenge of A10 DA cells with the partial DA autoreceptor agonist (–)‐3‐(3‐hydroxyphenyl)‐N‐n‐propylpiperidine [(–)3‐PPP], for which an autoreceptor reserve should not exist, produced slightly attenuated responses in APO‐treated rats (2 X 50 μg/kg/day). These findings provide evidence for the existence of spare somatodendritic DA autoreceptors on A10 DA cells with respect to potent DA agonists, suggesting that repeated administration of “autoreceptor‐selective” doses of DA agonists may not result in a diminished inhibition of DA neuronal activity.
Human cortical neurons contain both nicotinic and muscarinic acetylcholine receptors: An immunocytochemical double‐labeling study
Authors: Schröder Hannsjörg , Zilles Karl , Luiten Paul G. M. , Strosberg Andre D. , Aghchi Alireza 
Published: January 2005

AbstractUsing immunofluorescence histochemistry, in the human cerebral cortex neurons immunoreactive for both nicotinic and muscarinic acetylcholine receptor proteins could be demonstrated. Vibratome sections of biopsy and autopsy specimens of human temporal and occipital lobes were incubated with monoclonal antibodies specific for muscarinic (M 35) and nicotinic (WF 6) acetylcholine receptor protein. Immunoreactive sites were visualized using a biotin‐streptavidin‐phycoerythrin system (M 35, red fluorescence) and fluorescein‐conjugated immunoglobulins (WF 6, green fluorescence). Immunofluorescence of both antibodies was preponderant in pyramidal neurons located in layers II/III and V and their apical dendrites. Some round and ovoid immunolabeled cells were encountered in layers VI and IV. About 30% of the cholinoceptive cortical neurons, in particular the pyramidal cells, displayed immunoreactivity for both receptor types. The present investigation shows a subpopulation of human cortical neurons to contain both nicotinic and muscarinic receptors. The coexistence of acetylcholine receptors may provide the morphological basis of simultaneous impact of acetylcholine on both receptor types in the same neuron of the human cerebral cortex.
D1 dopamine receptor stimulation enables the postsynaptic, but not autoreceptor, effects of D2 dopamine agonists in nigrostriatal and mesoaccumbens dopamine systems
Authors: Wachtel Stephen R. , Hu Xiu‐Ti , Galloway Matthew P. , White Francis J. 
Published: January 2005

AbstractPossible functional interactions between D1 and D2 dopamine (DA) receptors were examined using extracellular single‐cell recording with microiontophoretic application of selective D1 and D2 receptor agonists both postsynaptically, in the rat nucleus accumbens (NAc) and caudate‐putamen (CPu), and presynaptically, at impulse‐regulating somatodendritic DA autoreceptors in the ventral tegmental area (A10) and substantia nigra pars compacta (A9) In addition, synthesis‐modulating nerve terminal DA autoreceptors were studied in both the CPu and NAc using the gammabutyrolactone (GBL) neurochemical model of isolated nerve terminal autoreceptor function in vivo.In both the NAc and CPu, the inhibition of neurons produced by iontophoresis of the D2 receptor agonists quinpirole or RU‐24213 was attenuated by acute DA depletion via the tyrosine hydroxylase inhibitor α‐methyl‐p‐tyrosine (AMPT). However, during iontophoresis of the selective D1 DA receptor agonist SKF 38393, the inhibitory effects of the D2 agonists were again evident, suggesting that the attenuation of D2 agonist‐induced inhibition was due to decreased D1 receptor activation. In contrast, the inhibitory effects produced by the non‐selective D1/D2 agonist apomorphine or by SKF 38393 were unaffected by AMPT pretreatment. Thus, D1 receptor activation appears necessary for D2 receptor‐mediated inhibition of NAc and CPu neurons, whereas D2 receptor activation is not required for the inhibition produced by D1 receptor stimulation.In contrast to postsynaptic D2 receptors, the ability of DA agonists to stimulate D2 DA autoreceptors was not altered by manipulations of D1 receptor occupation. Enhancing D1 receptor stimulation with SKF 38393 or reducing D1 receptor occupation with either the selective D1 receptor antagonist SCH 23390 or AMPT failed to alter the rate‐inhibitory effect of i.v. quinpirole on A9 or A10 DA neurons. Similarly, iontophoresis of SKF 38393 failed to alter the inhibitory effects of iontophoretic quinpirole. SKF 38393 also failed to affect the inhibition of GBL‐induced increases in DOPA accumulation (tyrosine hydroxylase activity) produced by quinpirole in either the NAc or CPu. Furthermore, reversal of GBL‐induced increases in DOPA accumulation by apomorphine or quinpirole was unaffected by pretreatment with SCH 23390. Therefore, D1 receptor occupation appears to be necessary for the expression of the functional effects of postsynaptic D2 receptor stimulation but not presynaptic D2 DA autoreceptor stimulation.
Autoradiographic quantification of serotonin1A receptors in rat brain following antidepressant drug treatment
Authors: Welner S. A. , De Montigny C. , Desroches J. , Desjardins P. , Suranyi‐Cadotte B. E. 
Published: January 2005

AbstractThere is growing evidence that the serotonergic (5‐HT) system is involved in the pathogenesis and treatment of major depression. The 5‐HT receptor subtype involved in the enhancing effect of antidepressant treatments, however, has not been identified. The present study was undertaken to quantify 5‐HT1A sites in the rat brain by autoradiography and membrane binding, using the selective ligand [3H]8‐hydroxy‐N, N‐dipropyl‐2‐aminotetralin (8‐OH‐DPAT), following long‐term antidepressant treatment. Following a 21‐day treatment with amitriptyline (10 mg/kg/day), there was a significant increase of [3H]8‐OH‐DPAT binding measured by autoradiography in the dorsal hippocampus, but there was no change in the nucleus raphe dorsalis; whole brain membrane binding revealed an increase in the number of binding sites, with no change in the affinity for [3H]8‐OH‐DPAT. Conversely, fluoxetine (10 mg/kg/day), a selective blocker of 5‐HT reuptake, and gepirone (10 mg/kg/day), a 5‐HT1A agonist, both administered for 21 days, significantly reduced [3H]8‐OH‐DPAT binding measured by autoradiography in the nucleus raphe dorsalis without altering hippocampal binding sites. The control active treatment with diazepam (2 mg/kg/day) did not alter [3H]8‐OH‐DPAT binding in the hippocampus or in the nucleus raphe dorsalis. All groups were compared to a 21‐day vehicle‐treated control group. These results are fully consistent with previous electrophysiological and behavioral studies and suggest that alterations of 5‐HT1A receptors might underlie the enhancement of 5‐HT neurotransmission by antidepressant treatments.
Stimulation of d2 dopamine receptors decreases intracellular calcium levels in rat anterior pituitary cells but not striatal synaptosomes: A flow cytometric study using indo‐1
Authors: Wolf Marina E. , Kapatos Gregory 
Published: January 2005

AbstractAn important question is whether all D2 dopamine (DA) receptors employ the same signal transduction mechanisms. Anterior pituitary cells and striatal synaptosomes, which possess pharmacologically similar D2 DA receptors, were compared with respect to the effect of D2 DA receptor stimulation on free intracellular Ca2+ levels ([Ca2+]i). Flow cytometry, in combination with either the fluorescent calcium indicator indo‐1 or fluorescent voltage‐sensitive dyes, was used to measure [Ca2+]i and to detect changes in membrane potential. In subpopulations of anterior pituitary cells, increases in [Ca2+]i were produced by elevated K+, veratridine, thyrotropin‐releasing hormone, and BAY K 8644. These increases were blocked by nifedipine, suggesting the involvement of L‐type voltage‐sensitive calcium channels (VSCC's). In 10–15% of the cells, D2 agonists decreased resting [Ca2+]i, reversed stimulus‐induced increases in [Ca2+]i, and caused a hyperpolarization. In striatal synaptosomes, elevated K+ and veratridine also increased [Ca2+]i. However, the K+‐induced increase was eliminated if choline was substituted for Na+ in the medium, suggesting that Ca2+ entry in response to sustained K+ depolarization resulted from reversal of Na+/Ca2+ exchange. Nifedipine and verapamil inhibited K+‐induced increases in [Ca2+]i only at concentrations greater than 10 μM, while ω‐conotoxin had no effect. D2 agonists had no effect on resting or stimulated [Ca2+]i but did hyperpolarize 10–20% of the synaptosomes, indicating that D2 DA receptors are functional in this preparation. The ability of pituitary but not striatal D2 DA receptors to modulate [Ca2+]i may reflect the fact that the two systems differ with respect to pathways for Ca2+ influx.
Morphological correlates of long‐term potentiation imply the modification of existing synapses, not synaptogenesis, in the hippocampal dentate gyrus
Authors: Desmond Nancy L. , Levy William B. 
Published: January 2005

AbstractThis report evaluates two morphological markers of synaptogenesis following the induction of long‐term potentiation (LTP) in the dentate gyrus of the anesthetized rat. These two morphological features, polyribosomes and multiple synaptic contacts, are known to increase in number with synaptogenesis in the mature hippocampus.The analysis focused on the middle third of the dentate molecular layer. As shown previously, this is the region of primary synaptic activation in our electrophysiological protocol and the region of localized morphological changes with LTP. Here the incidence of a polyribosome at the base of a dendritic spine declined 57% with LTP. In addition, the number of multiple synaptic contacts decreased 18% there with LTP. Both decreases were more pronounced immediately following conditioning stimulation than at later intervals. Beacause both morphological features decrease with LTP but increase with synaptogenesis, the data do not support the hypothesis that new synapses form with LTP. Instead, the data add further support to the view that the strengthening of existing excitatory synapses underlines LTP.
Levels of biogenic amines, their metabolites, and tyrosine hydroxylase activity in the human epileptic temporal cortex
Authors: Pintor Manuela , Mefford Ivan N. , Hutter Ingrid , Pocotte Susan L. , Wyler Allen R. , Nadi N. Suzan 
Published: January 2005

AbstractThe levels of serotonin (5‐HT), 5 hydroxyindoleacetic acid (5‐HIAA), dopamine (DA), homovanillic acid (HVA), norepinephrine (NE), and tyrosine hydroxylase (TH) activity were measured in the focus (spiking) and nonfocus (nonspking) regions of the temporal neocortex of 20 patients with intractable complex partial seizures. The levels of 5‐HT, DA, 5‐HIAA, and HVA were higher in the focus when compared to the nonfocus. Values for NE and TH activity were not different when focus and nonfocus were compared. The ratios of metabolite to precursor for 5‐HT and DA were not significantly different between the focus and the nonfocus, suggesting that the changes observed were the result of a modification in the synthesis and release of these amines. Such changes in the epileptic focus could be caused by altered transsynaptic regulatory processes, which occur as a result of neuronal loss, gliosis, or neuronal sprouting.
Effects of glycine on neurons in the rat substantia nigra zona compacta: In vitro electrophysiological study
Authors: Mercuri Nicola Biagio , Calabresi Paolo , Bernardi Giorgio 
Published: January 2005

AbstractThe effects of bath‐applied glycine to substantia nigra zona compacta neurons of rat were investigated byintracellular recording techniques in vitro. Superfusion of glycine (1 mM) in the medium hyperpolarized 53% of the neurons recorded with KCI electrodes, whereas 32% of the cells were depolarized. The remaining 15% of neurons was hyperpolarized and then depolarized by the amino acid. In spite of these membrane changes, the action potential firing was depressed. Both hyperpolarization and depolarization were correlated to an outward and an inward current, respectively, when recording in single‐electrode voltage‐clamp mode.In response to bath application of glycine, the neurons showed a concentration‐dependent conductance increase. Micromolar concentrations of glycine (100–300 m̈M) in the superfusion medium produced a membrane hyperpolarization (outward current) in most of the tested cells, whereas millimolar concentration of amino acid could cause depolarization (inward current) in the same neurons.When the recording electrodes contained K acetate, only hyperpolarizations (outward current) were produced. The potential and current changes and the increase in membrane conductance produced by glycine showed little desensitization when neurons were recorded with K acetate electrodes. The mean reversal potential for the membrane hypolarization was –80 mV with intracellular electrodes containing KCI and –84 mV with electrodes containing K acetate. The mean null potential for the depolarizing effect was –46 mV.The reversal potential for the glycinergic responses was shifted to less negative values upon lowering the extracellular concentration of chloride or increasing the extracellular concentration of potassium. Strychnine (1–10 m̈M) reversibly antagonized both the conductance increase and the membrane changes produced by glycine. Bath application of bicuculline (100 m̈M) and picrotxin (200 m̈M) did not affect glycine responses, while depressing the actions of GABA and muscimol.It is concluded the glycine exerts and inhibition on substantia nigra zona compacta neurons by acting on strychnine‐sensitive receptors. The membrane effects produced by glycine result from the activation of a cloride current. In addition, the simultaneous involvement of porassium ions may contribute to the overall effects of glycine.
Mapping muscarinic receptors in human and baboon brain using [N‐11C‐methyl]‐benztropine
Authors: Dewey Stephen L. , Macgregor Robert R. , Brodie Jonathan D. , Bendriem Bernard , King Payton T. , Volkow Nora D. , Schlyer David J. , Fowler Joanna S. , Wolf Alfred P. , Gatley S. John , Hitzemann Robbert 
Published: January 2005

AbstractThe muscarinic cholinergic system has been mapped in vivo inhuman and baboon brain using [N‐11C‐methyl]‐benztropine and high resolution positron emission tomography (PET). [N‐11C‐methyl]‐benztropine uptake was observed in frontal, parietal, occipital, and temporal cortices as well as in subcortical structures including the corpus striatum and thalamus. Uptake continued to increase in baboon and human brain in all areas over an 80 minute experimental period with the exception of the exception of the cerebellum wehere the accumulation of radioactivity began to decrease by 25 minutes potinjection. The ratio of incorporation of [N‐11C‐methyl]‐benztropine between corpus striatum/cerebellum was 1.53 and 1.46 in humans and baboons, respectively, at 60 minutes. Blocking studies in baboons using the muscarinic cholinergic antagonists scopolamine and benztropine and the muscarinic cholinergic agonist pilocarpine combined with blocking studies in humans using benztropine indicate that the binding of this compound is specific for the muscarinic cholinergic system. Pretreatment with the potent dopamine reuptake blocker nomifensine produced no effect on the incorporation of radioactivity in any baboon brain region examined. Analysis of labelled plasma metabolites indicates that in humans, the rate of metabolism of [N‐11C‐methyl]‐benztropine is slow (83.0% unchanged at 30 minutes postinjection) differeing quite dramatically from the rate of metabolism observed in baboons (43.4%% unchanged at 30 minutes postinjection). These data combined with postmortem studies in humans and primates demonstrate that [N‐11C‐methyl]‐benztropine is a suitablemuscarinic cholinergic ligand for use in humans and baboons with PET.
Anatomical localization of calmodulin mRNA in the rat brain with cloned cDNA and synthetic oligonucleotide probes
Authors: Roberts‐Lewis Jill M. , Cimino Mauro , Krause Rudolph G. , Tyrrell Daniel F. , Davis Leonard G. , Weiss Benjamin , Lewis Michael E. 
Published: January 2005

AbstractCalmodulin is a small, acidic calcium‐binding protein that regulates a number of calcium‐dependent enzyme activities and is thought to be involved in neurotransmission to begin to explore further the regulation of this important protein in the brain, we have cloned a rat calmodulin cDNA and designed an oligonucleotide probe based on this sequence. Both the cDNA and oligonucleotide probes revealed a markedly heterogeneous distribution of hybridization signal for calmodulin mRNA in the rat brain. The greatest apparent abundance of mRNA for calmodulin was seen in the hippocampus and cerebral cortex, whereas many brain regions showed relatively low hybridization signal, including the striatum and portions of the hypothalamus and brainstem.
Somatospiny neurons in the rat lateral septal area are synaptic targets of hippocamposeptal fibers: A combined EM/Golgi and degejeration study
Authors: Jakab Robert L. , Leranth Csaba 
Published: January 2005

AbstractThe mediolateral part of the lateral septal area (LSA) is a common target of hipocamposeptal afferents, neuropeptide containing, catecholaminergic, cholinergic, and GABAergic pericellular baskets of different origins. This specific innervation pattern as well as electrophysiological data concerning this area suggest a convergent input from different sources to particular LSA neuron populations. Light and electron microscopy combined with Golgi impregnation and acute anterograde degeneration techniques following ltransection of the fimbria‐fornix were employed to determine whether LSA neurons with hippocampal input have any characteristic and distinctive morphological signs. About 20% of all Golgi impregnated LSA neurons were found to have somatic spine. All of these somatospiny neurons are synaptic targets of hippocamposeptal fibers. The degenerated hippocamposeptal boutons establish asymmetric synaptic contacts on their soma, somatic and dendritic spines, and on dendritic shafts. Somatospiny neurons located in the most medial and dorsal parts of the LSA seem to project toward the medial septum while all of the others appear to send descending fibers to ventral areas. Somatospiny neuron axons occasionally give out recurrent collaterals. Quantitative analysis on the spatial distribution of the somatospiny neurons revealed that practically all of them are encountered in the mediolateral division of the LSA. This area includes the lateral part of the intermediolateral spptal nucleus and adjacent lateral portions of the dorsolateral and the ventrolateral sptal nuclei.
In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis
Authors: Nomikos George G. , Damsma Geert , Wenkstern Danielle , Fibiger Hans C. 
Published: January 2005

AbstractIn vivo brain microdialysis was used to characterize the effects of some dopamine uptake inhibitors on the extracellular concentrations of dopamine (DA) and its metabolitesdihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striata of awake, freely moving rats. d‐Amphetamine, GBR 12909, cocaine, nomifensine, methylphenidate, bupropion, and benztropine were administered directly to the striatum via the perfusion fluid in increasing concentrations (1–1,000 μM). All drugs increased extracellular DA in a dose‐dependent manner; however, only d‐amphetamine produced dose‐dependent decreases in DOPAC and HVAconcentrations. The shapes of the dose‐reponse functions differed considerably between the drugs. At 100 and 1000 μM d‐amphetamine had biphasic effects (an increase followed by a decrease) on dialysate DA concentration. GBR 12909, methylphenidate, and benztropine also had biphasic effects when applied at the 1,000 μM concentration. In contrast, cocaine, nomifensine, and bupropion produced relatively monophasic increases in extracellular DA. Tetrodotoxin (TTX), which prevents action potentials by blocking voltage‐dependent Na+ channels, did not prevent d‐amphetamine induced increases in extracellular DA, but blocked completely the effects of cocaine, nomifensine, bupropion, and methylphenidate. While low doses (10 μM) of GBR 12909 and benztropine were highly sensitive to TTX, the toxin was only partially effective against higher doses of the compounds. The rank order of potency of the drugs as determined by the increases in extracellular DA produced by 10 or 100 μM (following correction for dialysis efficiency of the test compounds in vitro) was GBR 12909< benztropine< amphetamine= nomifensine= methylphenidate< cocaine< bupropion. The in vivo characterization of changes in extracellular DA following direct, local application of DA uptake inhibitors can be used to provide useful information aboout the mechanisms of action and potency of these compounds.