Biomedical subjects
Publications and source records attributed to M T Taber.
The clinical significance of myocardial bridges (MBs) is variable, and most patients are asymptomatic. However, angina, myocardial infarction, and sudden death have been reported in association with MBs. Here we describe the use of intracoronary stenting for the treatment of a patient with an anterior myocardial infarction due to an MB.
The extent to which glutamate receptors in the nucleus accumbens and ventral tegmental area regulate feeding-evoked increases in dopamine release in the nucleus accumbens was determined using in vivo brain microdialysis in the rat. In some animals a second dialysis probe was implanted in the ventral tegmental area ipsilateral to the nucleus accumbens probe. The feeding protocol involved access to standard rat chow after 18 h of food deprivation. Under these conditions rats began eating approximately 30 s after the introduction of food and consumed 7-8 g, resulting in a 50% increase in dopamine release. Application of the glutamate receptor antagonist kynurenate (1 mM) in the nucleus accumbens potentiated the feeding-evoked increase in dopamine release by 80%. Application of the metabotropic glutamate receptor agonist trans-1S,3R-1-amino-1,3-cyclopentanedicarboxylic acid (100 microM) in the nucleus accumbens blocked the feeding-evoked increase in dopamine release. Application of a combination of the ionotropic glutamate receptor antagonists 2-amino-5-phosphopentanoic acid (200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (50 microM) through the dialysis probe in the ventral tegmental area reduced basal dopamine output in the nucleus accumbens by 20% and markedly attenuated (by 70%) the effect of feeding on dopamine release. None of the treatments affected the latency to eat or the volume of food consumed. These results indicate that glutamatergic afferents to the ventral tegmental area mediate feeding-induced increases in dopamine release in the nucleus accumbens. In contrast, at physiological concentrations, glutamate in the nucleus accumbens appears to decrease dopamine release via actions on ionotropic and metabotropic receptors.
Intracerebral microdialysis was used to investigate the effects of local application of L-glutamate, N-methyl-D-aspartate, and the glutamate uptake inhibitor 1-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) in the nucleus accumbens (NAc) on extracellular dopamine (DA) concentrations. The effects of locally applied PDC on extracellular glutamate concentrations were also examined. Glutamate produced a concentration-dependent decrease in extracellular DA that could be blocked by concurrent, local application of the broad spectrum ionotropic glutamate receptor antagonist kynurenic acid (KYN:1 mM). N-Methyl-D-aspartate had a concentration-dependent effect on DA release, with a low concentration (0.1 mM) producing a decrease and a higher concentration (1.0 mM) resulting in an increase. Both effects were blocked by KYN. PDC (1 mM) increased extracellular glutamate concentrations to 102% above baseline. The same concentration of PDC decreased extracellular DA concentrations, and coapplication of KYN attenuated this effect. These results indicate that glutamate receptor agonists can have both facilitatory and inhibitory effects on extracellular DA concentrations. However, the effects of PDC indicate that inhibition of DA release is the more physiologically relevant effect. Furthermore, the results of these and other experiments suggest that glutamate's inhibitory effects on DA release in the NAc are not due to direct actions of this excitatory amino acid on DA terminals. A multisynaptic model that accounts for glutamate's actions on DA release is proposed.
There is considerable neurophysiological evidence that chronically administered neuroleptics can, under certain circumstances, decrease the activity of mesencephalic dopaminergic neurons. This finding, referred to as depolarization inactivation or depolarization block, has led to the hypothesis that the delayed therapeutic effects of neuroleptic drugs are due to a graduate silencing of mesolimbic dopaminergic neurons. One prediction of depolarization inactivation is that dopamine neurons in this state should be resistant to activation by excitatory stimuli. As a test of this prediction, rats that had been treated chronically with either saline or haloperidol (0.5 mg/kg x 21 days) were exposed to either acute mild stress or electrical stimulation of the prelimbic region of the prefrontal cortex while extracellular levels of dopamine in the nucleus accumbens were monitored by in vivo microdialysis. A 10-minute exposure to acute stress via tail pinch increased dopamine release by 20% and 18% in the saline and haloperidol groups, respectively. Similarly, 20 minutes of cortical stimulation increased dopamine release by 51% and 56% in rats treated chronically with saline or haloperidol, respectively. These results indicate that contrary to a prediction of the depolarization block hypothesis, mesolimbic dopaminergic neurons can be activated in neuroleptic-treated animals.
In vivo microdialysis was used to determine the extent to which ionotropic glutamate receptors in the ventral tegmental area (VTA) regulate dopamine release in the nucleus accumbens. Coapplication of 2-amino-5-phosphonopentanoic acid (AP5; 200 microM) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 50 microM) to the VTA via reverse dialysis decreased extracellular concentrations of dopamine in the nucleus accumbens by approximately 30%. In accordance with previous results, electrical stimulation of the prefrontal cortex increased dopamine release by 60%. Application of AP5 and CNQX to the VTA during cortical stimulation blocked the effect of stimulation on dopamine release. These results indicate that ionotropic glutamate receptors in the VTA are critically involved in basal and evoked dopamine release in the nucleus accumbens and suggest that a glutamatergic projection from the prefrontal cortex regulates the activity of dopaminergic neurons in the VTA.
In vivo microdialysis was used to assess the effects of electrical stimulation of the prefrontal cortex (PFC) on dopamine (DA) release in the nucleus accumbens (NAC) of awake, unrestrained rats. The PFC was stimulated bilaterally for 20 min at parameters previously shown to support intracranial self-stimulation in this structure. Stimulation at 50 microA evoked a 38% increase in DA release while 100 microA produced a 69% increase. Thus, phasic activation of the PFC increases DA release in the NAC. Additional experiments were performed to establish whether glutamate receptors in the NAC mediated these effects. The noncompetitive NMDA antagonist dizocilpine maleate (MK-801) and the broad spectrum competitive antagonist kynurenic acid were each applied locally to the NAC via reverse dialysis alone or in combination with electrical stimulation of the PFC (100 microA). Both MK-801 (10 microM) and kynurenic acid (5 mM) increased DA release when administered alone. When a "subthreshold" concentration (i.e., the highest concentration employed that did not itself increase DA release) of either compound was administered together with PFC stimulation, neither kynurenic acid (1 mM) nor MK-801 (1 microM) attenuated the effect of stimulation on DA release, thereby indicating that this effect is not mediated by ionotropic glutamate receptors located within the NAC. To examine the possible role of metabotropic glutamate receptors in regulating DA release, the metabotropic glutamate agonist trans(1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) was employed. When applied locally to the NAC, ACPD had a dose-dependent effect on DA release with a high concentration (1 mM) causing an increase and a lower concentration (100 microM) causing a small decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
The effect of electrical stimulation of the prefrontal cortex (PFC) on acetylcholine (ACh) release in the dorsal striatum was investigated using on line in vivo microdialysis. ACh output was sampled before, during and after 20-min periods of 50 and 100 microA stimulation in awake, unrestrained rats. Both currents increased extracellular ACh by approximately 30% above baseline. ACh concentrations reached their maximum values during the last 10 min of the stimulation period and returned to baseline within 20 min. These results provide direct functional evidence for cortical modulation of cholinergic interneurons in the striatum.
Exogenous and endogenous glutamate has been shown to evoke dopamine (DA) release in the striatum using both in vitro and in vivo techniques. We hypothesized that stimulation of the prefrontal cortex (PFC) would phasically enhance striatal DA release via the glutamatergic corticostriatal pathway. To test this hypothesis, in vivo brain microdialysis was employed to measure extracellular concentrations of DA in the striatum during electrical stimulation of the PFC. Five rats were implanted with bilateral electrodes located in the medial PFC and dialysis probes in the dorsal striatum. Two days later the PFC of these awake, freely moving rats was stimulated first at 50 microA and then at 100 microA for 20 minutes at 2-hour intervals. Both currents significantly increased DA release. Extracellular DA rose rapidly during stimulation, peaked immediately afterward, and then slowly returned to baseline values. Dopamine reached 118% of baseline values with 50 microA stimulation and 138% with 100 microA stimulation. Histologic analysis using the fluorescent retrograde dye Fluoro Gold confirmed that cells projecting to the vicinity of the striatal dialysis probe originated in the vicinity of the PFC electrodes. These results provide direct evidence for phasic, excitatory modulation of striatal DA release by the PFC.