PubMed Health⌕ Search

Biomedical subjects

A A Grace

Publications and source records attributed to A A Grace.

At least 55 records · Page 3Linked to original sources
PubMed1999

Interaction of benztropine and haloperidol actions on rat substantia nigra dopamine cell electrophysiological activity in vivo.

Despite the known efficacy of antimuscarinic agents in treating dopamine-related movement disorders, their effects on dopamine cell activity have not been well studied. We investigated the effects of systemically administered benztropine, an antimuscarinic agent that also inhibits the dopamine transporter, on substantia nigra dopamine neuron electrophysiological activity. Benztropine caused a dose-dependent inhibition of the firing rate of dopamine neurons in control rats but exerted baseline-dependent changes in burst firing. In rats pre-treated with haloperidol, which prevents the effects of dopamine transporter inhibitors on dopamine cell activity, benztropine either increased or decreased firing rate; however, it consistently increased burst firing. Thus, the antimuscarinic and psychostimulant properties of benztropine have differential effects on dopamine neuron firing rate and burst firing. The increase in burst firing seen in the presence of haloperidol may mediate some of the therapeutic effects of benztropine in the treatment of antipsychotic drug-induced movement disorders.

Animals↗
PubMed1999

Alterations in electrophysiological activity and dye coupling of striatal spiny and aspiny neurons in dopamine-denervated rat striatum recorded in vivo.

We recently reported that pharmacological manipulations of the dopamine system can produce more than a 4-fold increase in dye coupling between dopaminoceptive neurons in the adult rat striatal complex. During in vivo intracellular recordings, striatal neurons in control rats and in rats that had been treated with 6-hydroxydopamine were injected with either Lucifer yellow or Neurobiotin. Only rats that exhibited severe loss (i.e., larger than approximately 95%) of striatal dopamine terminals displayed a significant increase in the incidence of dye coupling between neurons in adult striatum. Moreover, this increased coupling was present only between neurons of the same morphological cell class, i.e., among clusters of spiny neurons or between aspiny neurons. Combining intracellular labeling of spiny neurons with parvalbumin immunocytochemistry demonstrated that coupling did not occur between anatomically adjacent neurons that comprised immunocytochemically and morphologically distinct cell classes. Therefore, gap junction conductance as reflected by dye coupling appears to undergo upregulation as a consequence of compromises in nigrostriatal and mesolimbic dopamine transmission.

Animals↗
PubMed1999

Binding across time: the selective gating of frontal and hippocampal systems modulating working memory and attentional states.

Temporal binding via 40-Hz synchronization of neuronal discharges in sensory cortices has been hypothesized to be a necessary condition for the rapid selection of perceptually relevant information for further processing in working memory. Binocular rivalry experiments have shown that late stage visual processing associated with the recognition of a stimulus object is highly correlated with discharge rates in inferotemporal cortex. The hippocampus is the primary recipient of inferotemporal outputs and is known to be the substrate for the consolidation of working memories to long-term, episodic memories. The prefrontal cortex, on the other hand, is widely thought to mediate working memory processes, per se. This article reviews accumulated evidence for the role of a subcortical matrix in linking frontal and hippocampal systems to select and "stream" conscious episodes across time (hundreds of milliseconds to several seconds). "Streaming" is hypothesized to be mediated by the selective gating of reentrant flows of information between these cortical systems and the subcortical matrix. The physiological mechanism proposed for this temporally extended form of binding is synchronous oscillations in the slower EEG spectrum (< 8 Hz).

Attention↗
PubMed1999

Blockade of putative beta4- and beta1-adrenoceptors by carvedilol in ferret myocardium.

The putative beta4-adrenoceptor mediates positive inotropic effects, action potential shortening and arrhythmias in ferret ventricle. Here we compared the affinity of carvedilol at the putative beta4-adrenoceptor and beta1-adrenoceptor, activated by (+/-)-CGP 12177 and (-)-isoprenaline, respectively. In paced right ventricular preparations, carvedilol (0.01-10 micromol/l) was a simple competitive antagonist of the positive inotropic effects of (+/-)-CGP 12177 (slope of Schild-plot = 1.02, pK(B) = 6.8) and (-)-isoprenaline (slope of Schild-plot = 0.98, pK(B) = 8.1). Carvedilol also blocked putative beta4- and beta1-adrenoceptors of left ventricle, left atrium and sino-atrial pacemaker. Carvedilol therefore interacts with the putative beta4-adrenoceptor according to the law of mass action and may provide a lead in the development of putative beta4-adrenoceptor-selective antagonists.

Adrenergic beta-Agonists↗
PubMed1999

The utility of pacemaker evoked T wave amplitude for the noninvasive diagnosis of cardiac allograft rejection.

Previous work suggested that pacemaker evoked T wave amplitude (ETWA) may be a sensitive noninvasive marker of cardiac allograft rejection. A Topaz QT sensing rate responsive pacemaker (Vitatron Medical) was implanted at transplantation using epicardial ventricular leads in 45 recipients (35 males; median age 51 years, range 20-63). The median duration of follow-up was 129 days (range 4-327). The ETWA at a paced rate of 100 beats/min was measured daily during hospitalization and at each outpatient attendance (900 readings). Endomyocardial biopsies were at routine intervals or when otherwise clinically indicated (257 biopsies with concurrent ETWA data). There were 58 episodes of rejection > or = grade 3a in 28 patients. The biopsies were classed as either no rejection (grade < 3a) or rejection requiring treatment (grade > or = 3a). The median normalized ETWA was 100.8% (range 24.6-239.7) without rejection and 89.9% (17.0-189.7) with rejection (Mann-Whitney U Test: P = 0.028). The performance of ETWA monitoring as a diagnostic test for the individual recipient was evaluated with exponentially weighted moving average quality control charts. For the diagnosis of all rejection episodes, ETWA monitoring had a sensitivity of 55%, a specificity of 62%, a positive predictive value of 30%, and negative predictive value of 83%. It is concluded that although analysis of pooled data showed a significant reduction in normalized ETWA with biopsy proven rejection, ETWA monitoring requires further refinement to improve sensitivity before it can be considered a clinically useful technique for the non-invasive diagnosis of cardiac allograft rejection in individual recipients.

Adult↗
PubMed1998

Dopamine modulates the responsivity of mediodorsal thalamic cells recorded in vitro.

The mediodorsal thalamic nucleus (MD) receives convergent inputs from subcortical limbic structures that overlap with a dopaminergic (DA) innervation. In this study, we describe the effects of DA agonists on the basal and evoked electrophysiological activity of identified thalamic cells of rats recorded in vitro. Administration of the D1 agonist SFK 38393 (10 microM) did not produce a clear effect on the physiological properties of the thalamic cells recorded. In contrast, bath administration of the D2 agonist quinpirole (10 microM) resulted in an enhancement of membrane excitability, facilitation of the occurrence of low-threshold spikes (LTSs), and changes in the resting membrane potential of the thalamic cells tested. The quinpirole-mediated responses were reversed by administration of the D2 antagonist haloperidol. Results from experiments performed with different [K+] and K+ channel blockers suggest that the effects of quinpirole are mediated at least in part by changes in K+ conductances. The results from this study suggest that DA can modulate the excitability of thalamic cells and in turn may influence the way that the thalamocortical system integrates information.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1998

DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.

Dopaminergic neurons exert a major modulatory effect on the forebrain. Dopamine and adenosine 3',5'-monophosphate-regulated phosphoprotein (32 kilodaltons) (DARPP-32), which is enriched in all neurons that receive a dopaminergic input, is converted in response to dopamine into a potent protein phosphatase inhibitor. Mice generated to contain a targeted disruption of the DARPP-32 gene showed profound deficits in their molecular, electrophysiological, and behavioral responses to dopamine, drugs of abuse, and antipsychotic medication. The results show that DARPP-32 plays a central role in regulating the efficacy of dopaminergic neurotransmission.

Amphetamines↗
PubMed1998

Striatal extracellular dopamine levels in rats with haloperidol-induced depolarization block of substantia nigra dopamine neurons.

Correlations between substantia nigra (SN) dopamine (DA) cell activity and striatal extracellular DA were examined using simultaneous extracellular single-unit recordings and in vivo microdialysis performed in drug-naive rats and in rats treated repeatedly with haloperidol (HAL). Intact rats treated with HAL for 21-28 d exhibited significantly fewer active DA cells, indicating the presence of depolarization block (DB) in these cells. However, in rats that received surgical implantation of the microdialysis probe followed by a 24 hr recovery period, HAL-induced DA cell DB was reversed, as evidenced by a number of active DA neurons that was significantly higher than that in HAL-treated intact rats and similar to that of drug-naive rats. In contrast, using a modified probe implantation procedure that did not reverse SN DA neuron DB, we found striatal DA efflux to be significantly lower than in controls and significantly correlated with the reduction in DA neuron spike activity. Furthermore, although basal striatal DA efflux was independent of SN DA cell burst-firing activity in control rats, these variables were significantly correlated in rats with HAL-induced DA cell DB. Therefore, HAL-induced DB of SN DA neurons is disrupted by implantation of a microdialysis probe into the striatum using standard procedures. However, a modified microdialysis method that allowed reinstatement of DA neuron DB revealed that the HAL-induced inactivation of SN DA neurons was associated with significantly lower extracellular DA levels in the striatum. Moreover, the residual extracellular DA maintained in the presence of DB may, in part, depend on the burst-firing pattern of the noninactivated DA neurons in the SN.

Animals↗
PubMed1998

Depletion of dopamine in the prefrontal cortex decreases the basal electrophysiological activity of mesolimbic dopamine neurons.

One hypothesis regarding the etiology of schizophrenia proposes that disruption of the dopaminergic innervation of the prefrontal cortex leads to an increase in dopamine (DA) transmission in subcortical regions. In the present study, we examined the effect of 6-hydroxydopamine lesions of the medial prefrontal cortex (mPFC) dopamine innervation on the spontaneous electrophysiological activity of ventral tegmental DA neurons recorded in vivo. DA cell activity was assessed along three dimensions: (1) the relative proportion of DA neurons exhibiting spontaneous activity, (2) their basal firing rate, and (3) the mean percentage of spikes fired in bursts. In lesioned rats, DA neurons in the ventral tegmental area (VTA) exhibited a significantly slower mean firing rate, as well as a significant reduction in the percentage of spikes fired in bursts relative to controls. In contrast, depletion of DA in the mPFC did not have a significant effect on the relative proportion of VTA DA neurons exhibiting spontaneous activity. We suggest that by reducing the basal electrophysiological activity of VTA DA neurons, mPFC DA depletion may lead to an increase in the level of responsivity of the system to excitatory stimuli. Thus, the magnitude of increase in action potential-dependent DA release that occurs in response to a challenge may be augmented in lesioned rats.

Action Potentials↗
PubMed1998

Quinidine.

Explore the source record for details and available documents.

Animals↗
PubMed1998

Phencyclidine interferes with the hippocampal gating of nucleus accumbens neuronal activity in vivo.

The N-methyl-D-aspartate channel blocker phencyclidine is known to induce psychotic episodes in normal subjects and exacerbate psychosis in schizophrenics; however, its site of action is not clear. The prefrontal cortex, hippocampus, and basal ganglia are brain regions that appear to play a role in the pathophysiology of schizophrenia, and therefore are the most likely to be involved in the psychotomimetic action of phencyclidine. In this study, systemic administration of phencyclidine reduced the frequency and duration of the spontaneously occurring depolarized plateaus observed in the membrane potential of accumbens neurons recorded intracellularly in vivo. Furthermore, recordings from rats pretreated with phencyclidine yielded proportionately fewer neurons showing depolarized events compared with untreated animals. These results suggest that phencyclidine may interfere with the generation of the depolarized ("up") state of the accumbens neuron membrane potential, which we had previously shown is dependent upon hippocampal input and is necessary for action potential discharge in these neurons. This action of phencyclidine is proposed to impair the flow of cortical information through the nucleus accumbens, and thereby mimic the consequences of the hippocampal deficit proposed to contribute to the pathophysiology of schizophrenia.

Action Potentials↗
PubMed1998

Response of the ventral pallidal/mediodorsal thalamic system to antipsychotic drug administration: involvement of the prefrontal cortex.

Intracellular recordings were obtained from rat ventral pallidal (VP) and mediodorsal thalamic (MD) cells in vivo and the effects of antipsychotic drugs on their basal and evoked electrophysiological characteristics were assessed. Administration of either haloperidol or clozapine caused a significant decrease in the average firing rate, accompanied by a hyperpolarization of the membrane potential in the VP cells recorded. However, neither drug induced a substantial change in the other basic membrane properties of the MD cells or VP cells tested. In addition, in 50% of the MD cells tested, both antipsychotic drugs caused a change in spike discharge from an oscillatory pattern to a tonic discharge mode. In rats that had received ibotenic acid lesions of the prefrontal cortex (PFCtx) 4-8 weeks prior to recording, cells in the VP exhibited similar changes in firing frequency in response to haloperidol administration as those in the intact rats. However, in contrast to the intact rats, MD cells recorded from rats with PFCtx lesions exhibited a significant increase in firing rate after haloperidol administration. The results from this study suggest that the prefrontal cortex plays a role in modulating the response of the thalamus to antipsychotic drugs.

Animals↗
PubMed1998

Catecholamines in the central nervous system. Overview.

A goal of this part is to examine the functional impact of catecholaminergic systems on CNS function as it relates to normal and pathological states. The participants achieve their objectives individually by relating their high-quality work on this expansive topic, while maintaining a focus on the functional implications of their findings. Nonetheless, despite the necessarily broad nature of the topics presented, there is a remarkable degree of convergence of information. Several subthemes have emerged as a consequence of considering this work in its entirety. First is the importance of examining neurotransmitter effects, not in isolation, but in terms of interactions with other neurotransmitter systems. History has shown that a limited focus often produces confusing or inconsistent results, which become increasingly clear on consideration of the state of the organism. Second is the importance of examining pharmacological and pathophysiological interactions in light of the anatomy of the system and how developmental influences can alter this relationship. Such very general considerations have been found to provide an essential ingredient in understanding the nature of catecholamine function within this complex system.

Afferent Pathways↗
PubMed1998

Action potential shortening through the putative beta4-adrenoceptor in ferret ventricle: comparison with beta1- and beta2-adrenoceptor-mediated effects.

The electrophysiological responses to (-)-CGP 12177 ((-)-4-(3-tertiarybutylamino-2-hydroxypropoxy) benzimidazol-2-one), an agonist for the putative beta4-adrenoceptor, were investigated on isolated perfused ferret hearts paced at 100 min(-1) and compared to those of (-)-noradrenaline and (-)-adrenaline, mediated through beta1- and beta2-adrenoceptors respectively. The three agonists decreased ventricular monophasic action potential duration but prolonged the action potential plateau; beta3-adrenoceptor-selective agonists had no effect. (-)-CGP 12177 was the most potent, but (-)-noradrenaline the most efficacious; both agonists caused ventricular extra-systoles. Because only (-)-noradrenaline but not (-)-CGP 12177 elicited shortening of the refractory period, the mechanism of arrhythmias mediated through beta1- and putative beta4-adrenoceptors may be different.

Action Potentials↗
PubMed1998

New models of the pathophysiology of schizophrenia: editors' introduction.

New models of the pathogenesis of schizophrenia are presented. These models represent hypotheses intended to stimulate discussion and new experimentation. Each of the contributions approach the pathophysiology of schizophrenia from a unique perspective. Yet, all of them emphasize the integration of new advances in basic neuroscience, the functional neuroanatomy of schizophrenia, and information drawn from new biotechnologies, such as neuroimaging and molecular genetics, to provide unique insights into schizophrenia. In each case, the novel hypotheses proposed also illustrate the continuing need for a better understanding of the dynamic interaction between synaptic plasticity and neural circuitry to further our understanding of the human brain in health and disease.

Humans↗
PubMed1998

Dysfunctions in multiple interrelated systems as the neurobiological bases of schizophrenic symptom clusters.

The absence of an animal model that accurately approximates schizophrenia limits current research into the pathophysiology of this disorder. Obviously, the cognitive disturbances associated with schizophrenia are difficult to evaluate in laboratory animals. Nonetheless, animal studies have provided insight into the anatomy and physiology of the brain systems that have been implicated in schizophrenia. These studies also suggest how brain systems may be involved in information processing in normal and pathological conditions. Thus, a careful assessment of the properties and functions of the brain regions suggested to be involved in schizophrenic symptoms has been a primary objective in several laboratories. In this review, we discuss the interactions among the brain regions implicated in schizophrenia--the ventral striatum, prefrontal cortex, hippocampus, and dopamine systems--and provide an integrative model linking altered function in these regions with specific clusters of symptoms of schizophrenia.

Animals↗
PubMed1998

Entrapment of an ablation catheter in the cardiac venous system: a case report.

Cannulation of the coronary sinus is a common procedure with infrequent complications. We report an unusual case of a steerable "dumb-bell" catheter passed through the ostium of the coronary sinus prior to an intended radiofrequency ablation procedure becoming stuck and requiring general anesthesia for extraction. We caution against the use of such catheters with a "waist" for the cannulation of the coronary sinus.

Adult↗