bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethanol differentially modulates GABAA receptor‐mediated chloride currents in hippocampal, cortical, and septal neurons in rat brain slices
Authors: Soldo Brandi L. , Proctor William R. , Dunwiddie Thomas V. 
Published: December 2004

AbstractPrevious electrophysiological studies have reported conflicting results concerning the effects of ethanol on γ‐aminobutyric acid‐A (GABAA) receptor‐mediated responses in the brain. To examine the variables that might explain these inconsistencies, the present study was designed to determine whether ethanol modulation of synaptically evoked GABA responses is brain region dependent, to identify factors that might regulate ethanol sensitivity, and to investigate the mechanism(s) underlying ethanol modulation of GABA responses. Whole‐cell voltage clamp methods were used to examine the effects of ethanol on synaptically evoked GABAA inhibitory postsynaptic currents (IPSCs) recorded from neurons in hippocampus, cerebral cortex, and intermediate lateral and medial septum from rat brain slice preparations. Bicuculline‐sensitive IPSCs elicited by local stimulation were pharmacologically isolated by pretreatment with the glutamate specific antagonists, DL‐(−)‐2‐amino‐5‐phosphonovaleric acid (APV) and 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX). Superfused ethanol (80 mM) potentiated evoked GABAA IPSCs in cortical neurons and in intermediate lateral and medial septal neurons but not in CA1 hippocampal neurons. However, the mechanism by which ethanol enhanced GABAA IPSC amplitudes differed between brain regions. In cortex, ethanol induced a hyperpolarizing shift in the GABAA IPSC reversal potential (EIPSC) without modifying the underlying GABAA receptor‐mediated conductance (GIPSC). In contrast, ethanol enhanced GABAA IPSC amplitudes in lateral and medial septal neurons by increasing the GIPSC without modifying the EIPSC These results suggest that ethanol differentially modulates responses to endogenous GABA released during synaptic activation and that important differences between various brain regions may reflect multiple mechanisms of ethanol action. © 1994 Wiley‐Liss, Inc.
Properties of inhibitory and excitatory synapses between hippocampal neurons in very low density cultures
Authors: Wilcox Karen S. , Buchhalter Jeffrey , Dichter Marc A. 
Published: December 2004

AbstractThe whole cell patch clamp technique was used to examine the electrophysiological properties of embryonic hippocampal neurons maintained in a very low density (VLD) culture prejparation. The goal of these experiments was to establish the viability of the VLD culture as a model system in which to study regulation of neurotransmission at single monosynaptic connections, in the absence of polysynaptic innervation. Depolarization of neurons in the VLD culture revealed voltage‐dependent sodium, calcium, and potassium currents which were blocked with, respectively, tetrodotoxin (TTX), cobalt, and tetraethylammonium and 4‐aminopyridine. When pairs of neurons were simultaneously recorded, action potentials evoked in presynaptic neurons elicited either excitatory or inhibitory postsynaptic currents (EPSCs or IPSCs, respectively). The dual component “EPSCs” were due to the activation of both types‐of postsynaptic, ionotropic glutamate receptors: N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors. Evoked IPSCs were due to the activation of postsynaptic γ‐aminobutyric acid (GABA) receptors. Both excitatory and inhibitory synapses exhibited short term depression in response to high frequency stimulation, although IPSCs were routinely decreased to a much greater degree than EPSCs. Spontaneous miniature EPSCs and IPSCs were found to persist in TTX, were blocked by the same pharmacological antagonists which blocked evoked responses, increased in frequency in response to hyperosmotic solution, and were unaffected by changes in extracellular calcium concentration. mIPSCS were found to occur at a significantly lower frequency than mEPSCs. These experiments indicated that neurotransmission in the VLD cultures occurs in a manner consistent with the quantal hypothesis and, therefore, the VLD culture is a good model for studying excitatory and inhibitory neurotransmission between isolated pairs of neurons. In addition, these experiments, performed under comparable physiological conditions, demonstrated that there are fundamental differences underlying neurotransmitter release between excitatory and inhibitory neurons. © 1994 Wiley‐Liss, Inc.
Acute administration of alcohol blocks cocaine‐induced striatal c‐fos immunoreactivity protein in the rat
Authors: Torres German 
Published: December 2004

AbstractImmediate‐early genes, such as c‐fos, are induced in the brain by cocaine and other psychotropic drugs. This induction is thought to be mediated via the activation of dopamine D1 and glutamate N‐methyl‐D‐aspartate (NMDA) receptor subtypes. Because alcohol selectively blocks NMDA receptor function, we determined the ability of alcohol to block the expression of c‐fos normally induced by systemic cocaine exposure in perikarya of the rat striatum. Acute administration of alcohol (2 g/kg; IP) approximately 30 min prior to a single cocaine (20 mg/kg) injection significantly reduced the patchy appearance of intensely immunoreactive gene signal in dorsal‐central quadrants of the caudate putamen. Separate administration of three doses of alcohol alone (1, 2, or 3 g/kg) was ineffectual in inducing FOS‐like protein in this or other regions of the rat brain. The blockade of the encoded protein by alcohol was partial in magnitude reminiscent of that produced by MK‐801 and related NMDA receptor antagonist drugs. Furthermore, the blockade of cocaine‐induced FOS‐like protein by alcohol occurred at a dose which produced a blood alcohol concentration of approximately 180 mg/dl (40 mM), comparable to that detected in intoxicating humans. Considering the fact that the concomitant use of alcohol and cocaine is the most common substance abuse pattern found in the addictive population, the present results suggest an antagonistic effect exerted by these two drugs at the transcriptional level and further support the consensus that NMDA receptors are the plausible surface‐target elements mediating some of the effects of alcohol and cocaine. © 1994 Wiley‐Liss, Inc.
Differences in the Cs block of baclofen and 4‐aminopyridine induced potassium currents of guinea pig CA3 neurons in vitro
Authors: Jarolimek Wolfgang , Bijak Maria , Misgeld Ulrich 
Published: December 2004

AbstractSingle‐electrode current‐ and voltage‐clamp techniques were employed to study responses elicited by (−)baclofen or γ‐aminobutyric acid (GABA) and 4‐aminopyridine (4‐AP) induced inhibitory postsynaptic potentials in CA3 pyramidal neurons in guinea pig hippocampal slices. All drugs were applied by the bath to submerged slices in which fast synaptic transmission was blocked by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (10 μM), bicuculline (50 μM), and picrotoxin (50 μM). (−)Baclofen (0.5 μM) and GABA (1 μM) induced equivalent‐sized hyperpolarizations and input resistance decreases. The agonist induced hyperpolarization or current and 4‐AP induced hyperpolarizations or currents (4‐AP induced K‐IPSPs or IPSCs) reversed in sign near the K‐equilibrium potential (EK). The GABAB receptor antagonists, OH‐saclofen (500 μM) and CGP 35348 (100 μM), reduced (−)baclofen responses, and 4‐AP induced K‐IPSPs, suggesting that they were mediated by GABAB receptors. Intracellular tetraethylammonium‐, and extracellular barium‐ions (1 μM) diminished the (−)baclofen induced current and 4‐AP induced K‐IPSCs. Intracellular Cs‐ions blocked the (−)baclofen induced outward current at resting membrane potential but did not grossly affect the inward current recorded at membrane potentials negative to EK. 4‐AP induced inwardly or outwardly directed KIPSCs were not blocked by intracellular Cs‐ions. Extracellular Cs‐ions (5 μM) blocked the (−)baclofen induced inward K‐current, but did not block 4‐AP induced inwardly directed K‐IPSCs. In conclusion, we found differences in the Cs block of K‐channels activated by (−)baclofen or the endogenous transmitter GABA. One reason could be that (−)baclofen predominantly activated extra synaptic GABAB receptors provided that extrasynaptic and subsynaptic receptors couple to different potassium channels. © 1994 Wiley‐Liss, Inc.
5‐HT1a agonist ±‐ 8‐OH‐DPAT modulates basal and stress‐induced changes in medial prefrontal cortical dopamine
Authors: Rasmusson Ann M. , Goldstein Lee E. , Deutch Ariel Y. , Bunney Benjamin S. , Roth Robert H. 
Published: December 2004

AbstractSerotonergic 5‐HTla agonists have recently been suggested to be effective in the treatment of human anxiety disorders. The neural mechanisms responsible for their clinical efficacy are unknown. In this study we investigated the effects of ±8‐hydroxy‐2(di‐n‐propylamino)tetralin [±8‐OH‐DPAT], a serotonergic,5‐HTIa agonist, on basal and stress‐induced changes in dopamine utilization and release in selected forebrain dopamine terminal fields in the rat. Dopamine utilization and release were respectively assessed by neurochemical analysis of ex vivo brain tissue and by microdialysis in the freely moving animal. Systemic ±8‐OH‐DPAT at doses below 225 μg/kg had no effect in any region except to slightly decrease dopamine utilization in the nucleus accumbens. However, at a dose of 225 μg/kg, ±8‐OH‐DPAT significantly increased basal dopamine utilization and release in the medial prefrontal cortex, while simultaneously decreasing serotonin release in this area. By contrast, the same dose of ±8‐OH‐DPAT decreased extracellular dopamine in the striatum. The effect of ±8‐OH‐DPAT on the response of the dopamine system to mild footshock stress was also assessed. This 5‐HTla agonist diminished the magnitude of footshock‐induced increases in prefrontal cortical dopamine utilization. These data suggest that 5‐HTIa agonists may dose‐dependently modulate both basal and stress‐induced changes in dopamine utilization in the medial prefrontal cortex. The possible relevance of these findings to the observed clinical efficacy of 5‐HT1a agonists in anxiety disorders is discussed. ©1994 Wiley‐Liss, Inc.
Binding of 125I‐iodovinyltetrabenazine to CNS vesicular monoamine transport sites
Authors: Kung Mei‐Ping , Canney Daniel J. , Frederick Dana , Zhuang Zheng , Billings Jeffrey J. , Kung Hank F. 
Published: December 2004

AbstractBinding characteristics of a novel radioiodinated tetrabenazine (TBZ) analog (iodovinyltetrabenazine; 125I‐TBZ‐Fraction I) were evaluated. In rat striatal homogenates, 125I‐TBZ‐I displayed a pharmacological profile consistent with specific binding to vesicular monoamine transport (VMAT) sites. In vitro autoradiographic studies using rat brain sections; further demonstrated that 125I‐TBZ‐I labeled the regions rich in VMAT sites, and it may be a useful marker for these sites. This novel radioiodinated ligand, with high specific activity and high binding affinity, may provide a powerful tool for the in vitro assessment of neuronal loss in various neurodegenerative diseases. © 1994 Wiley‐Liss, Inc.
Differential effect of MK 801 and scopolamine on c‐fos expression induced by L‐dopa in the striatum of 6‐hydroxydopamine lesioned rats
Authors: Morelli Micaela , Pinna Annalisa , Fenu Sandro , Carta Anna , Cozzolino Alberto , Di Chiara Gaetano 
Published: December 2004

AbstractIn rats with a unilateral 6‐hydroxydopamine lesion of the dopaminergic nigro‐striatal pathway, striatal Dl‐receptor‐stimulated c‐fos expression and turning behavior are positively modulated by D2 receptor stimulation and by blockade of N‐methyl‐D‐aspartate (NMDA) or muscarinic receptors. Combined D1/D2 receptor stimulation by L‐dopa activates c‐fos in a manner not additive with muscarinic receptor blockade by scopolamine. On the other hand, blockade of NMDA receptors by MK 801 reduced c‐fos expression induced by L‐dopa while, depending on the dose of L‐dopa, differentially affecting contralateral turning behavior. The results are interpreted to suggest that D2 receptor stimulation amplifies D1‐receptor‐mediated c‐fos expression by two mechanisms differentially related to muscarinic and NMDA receptors. ©1994 Wilev‐Lisa. Inc.
Alterations in TRH receptors in temporal lobe of schizophrenics: A quantitative autoradiographic study
Authors: Lexow Nedra , Joyce Jeffery N. , Kim Soo Jin , Phillips Jennifer , Casanova Manuel F. , Bird Edward D. , Kleinman Joel E. , Winokur Andrew 
Published: December 2004

AbstractWe utilized quantitative autoradiography to determine the distribution of receptors for thyrotropin‐releasing hormone (TRH) throughout the human temporal lobe and to examine the distribution of these receptors in discrete subregions of the temporal lobe from patients diagnosed premortem with schizophrenia. When compared to non‐neurologic controls, schizophrenic patients demonstrated an increase of 51% in the concentration of TRH receptors in the molecular layer of the dentate gyrus. Within nuclei of the schizophrenic amygdala, marked decreases were found in the central (44%), medial (38%), cortical (36%), accessory cortical (52%), lateral (54%), and medial basal (22%) nuclei. We also examined postmortem brain samples from patients with Huntington's disease, amyotrophic lateral sclerosis, and Alzheimer's disease for alterations in the distribution of TRH receptors. No significant differences from non‐neuropsychiatric controls were noted within the hippocampus in any of these disease states; however, slight alterations were noted in the central and medial basal amygdala in Huntington's disease and in the cortical amygdala in Alzheimer's disease. These disease‐specific findings suggest that TRH may play a role in the neurochemical dysfunction of schizophrenia. © 1994 Wiley‐Liss, Inc.
Glutamatergic antagonists attenuate ability of dopamine uptake blockers to increase extracellular levels of dopamine: Implications for tonic influence of glutamate on dopamine release
Authors: Moghaddam Bita , Bolinao Maria L. 
Published: December 2004

AbstractPrevious in vivo studies reporting a dose‐dependent increase in extracellular dopamine (DA) levels by excitatory amino acid (EAA) antagonists have been interpreted to indicate a lack of tonic excitatory effect exerted by these amino acids on striatal DA release. Alternatively, a tonic excitatory influence on DA release may affect a small fraction of DA terminals, so that blockade of this effect does not make a great enough contribution to the extracellular fluid to be detected by microdialysis. To examine this possibility, the effect of EAA antagonists was assessed by microdialysis in the presence of DA uptake blockers. It was found that in the presence of nomifensine or cocaine, antagonists of either NMDA or AMPA/kainate receptors decreased extracellular DA levels in the striatum. These data suggest that EAAs may exert a tonic facilitatory influence on striatal DA release and/or that endogenous EAAs may potentiate the action of DA uptake blockers through mechanisms that are mediated by EAA receptors. © 1994 Wiley‐Liss, Inc.
NMDA receptors mediate amphetamine‐induced upregulation ofzif/268and preprodynorphin mRNA expression in rat striatum
Authors: Wang John Q. , Daunais James B. , McGinty Jacqueline F. 
Published: December 2004

AbstractThe role of N‐methyl‐D‐aspartate (NMDA) excitatory amino acid receptors in D‐amphetamine (AMPH)‐induced behavioral changes and increased expression of the nuclear transcription factors, c‐fosandzif/268, and preprodynorphin (PPD) mRNA in various regions of rat forebrain was investigated with quantitative in situ hybridization histochemistry. Three hours after a single injection of AMPH (5 mg/kg, i.p.), the mRNA expression ofzif/268, but not c‐fos, in dorsal striatum (caudate nucleus) and cerebral cortex (sensorimotor cortex), and PPD mRNA in dorsal striatum, was upregulated. Pretreatment of rats with MK‐801 (0.5 mg/kg, i.p.) attenuated AMPH‐induced striatal and cortical expression ofzif/268mRNA and striatal expression of PPD mRNA, without affecting the behavioral alterations induced by AMPH. A similar, dose‐dependent suppression of AMPH‐inducedzif/268and PPD mRNA in striatum and cortex was also revealed after systemic administration of (±)‐3‐(2‐carboxypiperazin‐4‐yl)‐propyl‐l‐phosphonic acid (CPP) at doses of 5 and 10 mg/kg. CPP, only at the higher dose, slightly attenuated behavioral activity induced by AMPH. MK‐801 and CPP (at higher dose) alone suppressed basal (constitutive)zif/268mRNA levels in both striatum and cortex regions. No significant effect of either antagonist was found on constitutive expression of striatal PPD mRNA. These studies indicate that NMDA receptors mediate, at least in part, activation ofzif/268and PPD gene expression in striatum and sensorimotor cortex by a single injection of AMPH. Furthermore, NMDA receptor‐mediated gene regulation more likely is involved in long‐term neuronal plasticity to drug exposure than in acute drug effects since NMDA receptor antagonists had little or no effect on the acute behavioral actions of AMPH. © 1994 Wiley‐Liss, Inc.
In vivo binding of [123I]4‐(2′‐methoxy phenyl)‐1‐[2′‐(N‐2″‐pyridinyl)‐P‐iodobenzamido‐]ethyl‐piperazine, p‐MPPI, to 5‐HT1A receptors in rat brain
Authors: Kung Mei‐Ping , Zhuang Zhi‐Ping , Frederick Dana , Kung Hank F. 
Published: December 2004

AbstractThe in vivo regional distribution and pharmacological profile of a novel iodinated phenylpiperazine derivative, [123I]p‐MPPI (4‐(2′‐methoxy‐)phenyl‐l‐[2′‐(N‐2″pyridinyl)‐p‐iodobenzamido‐]ethyl‐piperazine), in the rat brain were evaluated for use as a potential in vivo imaging agent for 5‐HT1A receptors. The new ligand penetrated the blood‐brain barrier quickly and efficiently, with 1.2% of the injected dose found in the whole brain at 2 min post i.v. injection. The rate of radioactivity washout was slowest from the hippocampal region, followed by the hypothalamus, cortex, striatum, and cerebellum. The maximum ratio of hippocampus/cerebellum was 3.3 at 30 min postinjection. The specific binding of the radioligand in the hippocampal region, an area rich in 5‐HT1A receptor density, was blocked by pretreatment with a dose of (±) 8‐OH‐DPAT (2 mg/kg, i.v.) or WAY 100635 (1 mg/kg, i.v.), whereas the regional distribution of [123I]p‐MPPI was unaffected by pretreatment with non‐5‐HT1A agents such as ketanserin or haloperidol. Ex vivo autoradiographic studies further confirmed that the specific binding of [123I]p‐ MPPI is associated with 5‐HT1A receptor sites. These results indicate that [123I]p‐MPPI may be a useful candidate for noninvasive single photon emission computed tomography (SPECT) imaging of 5‐HT1A receptor sites in the living human brain. © 1994 Wiley‐Liss, Inc.
Dopamine D2 and D3 receptors in the rat striatum and nucleus accumbens: Use of 7‐OH‐DPAT and [125I]‐Iodosulpride
Authors: Booze Rosemarie M. , Wallace David R. 
Published: December 2004

AbstractA novel dopamine receptor mRNA transcript has been identified and classified as the D3 receptor subtype. We have examined the binding of the D2/D3‐selective compound [125I]‐Iodosulpride using unlabeled D3‐selective 7‐OH‐DPAT to determine the distribution of D2 and D3 dopamine receptor subtypes in the rat basal forebrain. Use of [125I]‐labeled ligands has significant advantages over [3H]‐labeled compounds for autoradiographic studies, especially for evaluating small brain areas containing low receptor densities. [125I]‐Iodosulpride identified two sites with high affinity (<1 nM) in the presence of (‐)sulpiride (μM; D2+3) or 7‐OH‐DPAT.(10 nM; D3), with a greater density of D2 receptors (twofold) compared to D3 receptors in the striatum. The density of D2 and D3 receptor subtypes displayed a 1:1 ratio in the nucleus accumbens. [125I]‐Iodosulpride with 7‐OH‐DPAT displayed D2 sites, predominately in the striatum. Digital subtraction autoradiography showed the highest levels of D3 binding in the islands of Calleja as well as in the core and shell regions of the nucleus accumbens. In sum, the advantages in using [125I]‐Iodosulpride to label the dopamine receptor subtypes are high specific activity, affinity, and lack of quenching in autoradiographic analyses. Moreover, masking D3 receptors with 7‐OH‐DPAT permitted indirect determination of D3 receptor density and localization using the [125I]‐labeled ligand, without the potential confound of 7‐OH‐DPAT binding to sigma receptors. The colocalization of the D2 dopamine receptors with D3 receptors suggests that unique interactions may exist between the receptor subtypes in the rat basal forebrain region. © 1995 Wiley‐Liss, Inc.
A genetic deficiency in calpastatin and isovalerylcarnitine treatment is associated with enhanced hippocampal long‐term potentiation
Authors: Muller D. , Molinari I. , Soldati L. , Bianchi G. 
Published: December 2004

AbstractThe Milan hypertensive strain (MHS) of rats, in addition to having hypertension, is also characterized by a genetic deficiency in calpastatin, the endogenous inhibitor of calpain. Since this protease has been implicated in long‐term potentiation (LTP), we have investigated whether induction of this form of plasticity was altered in this strain of rats as compared to control animals (Milan normotensive strain, MNS). Progressive induction of LTP by increasing numbers of high frequency trains resulted in a greater degree of potentiation measured with all inducing protocols in MHS as compared with MNS animals. This difference was not related to the hypertension, since another hypertensive strain (the SHR strain) and a segregated Milan hypertensive strain, expressing only the hypertention but not the calpastatin deficiency (the MHNE strain), exhibited an LTP indistinguishable from control rats. Treatment of MHNE rats for 2 months with isovalerylcarnitine, a compound that increases calpain activity, also resulted in a greater amount of LTP induced by high frequency trains. These effects were not related to an enhancement of the NMDA receptor dependent component of responses to burst stimulation. These results are consistent with the idea that conditions under which calpain activation is facilitated are associated with a greater degree of synaptic potentiation. © 1995 Wiley‐Liss, Inc.