Biomedical subjects

George V Rebec

Publications and source records attributed to George V Rebec.

24 records · Page 2Linked to original sources

PubMed2003

Lidocaine inactivation of ventral subiculum attenuates cocaine-seeking behavior in rats.

The role of the ventral subiculum in cocaine- or cue-induced cocaine-seeking behavior was investigated in rats tested on a between-session reinstatement model. Rats were trained to self-administer cocaine (0.25 mg/infusion, i.v.) in a lever-pressing operant task in a daily 2 hr session. Responding was reinforced contingent on a modified fixed-ratio 5 schedule. Reinstatement tests began after the lever-pressing behavior was extinguished in the absence of cocaine and conditioned cues (light and tone). Bilateral microinjections of lidocaine (100 microg) into the ventral subiculum decreased cocaine- or cue-induced reinstatement of cocaine-seeking behavior compared with saline microinjections into the same area in another group of rats. Lidocaine microinjections, however, had no effect on cocaine self-administration behavior or food-maintained or food-reinstated responding. Collectively, these results suggest that the ventral subiculum plays an important role in cocaine-seeking behavior. Considering the role of this structure in context learning, our data suggest that the full expression of cocaine- or cue-induced reinstatement may depend on the context in which the cocaine experience occurred.

Anesthetics, Local↗

PubMed2003

Ascorbate treatment attenuates the Huntington behavioral phenotype in mice.

The R6/2 mouse line expresses exon 1 of the human gene for Huntington disease (HD) and shows behavioral symptoms as early as 6 weeks of age. In the striatum, a forebrain target of HD, these animals show a behavior-related deficit in extracellular ascorbate, the deprotonated form of vitamin C. We report here that this deficit may contribute to the HD behavioral phenotype. Regular injections of ascorbate (300 mg/kg/day, 4 days/week) beginning at symptom onset restored the behavior-related release of ascorbate in striatum and also improved behavioral responding. Compared to vehicle, ascorbate treatment significantly attenuated the neurological motor signs of HD without altering overall motor activity. Ascorbate regulation of striatal function appears key for understanding HD.

Animals↗

PubMed2003

Characterization of striatal activity in conscious rats: contribution of NMDA and AMPA/kainate receptors to both spontaneous and glutamate-driven firing.

Single-unit activity in the striatum of unrestrained, conscious rats was characterized by extracellular recording in combination with iontophoresis. To avoid the confounding effect of motor-related changes in firing rate, measurements were restricted to periods when animals were at quiet rest. Recording electrodes were lowered stepwise through 4.0 mm of anterior striatum in 36 equal ventral movements of 111 microm to assess the ratio of spontaneously active vs. silent neurons. Spontaneous activity was assessed at each step followed by iontophoretic glutamate (GLU) application to expose silent neurons. Eleven such experimental sessions resulted in a total of 100 spontaneously active and 264 silent neurons, indicating that without overt movement the large majority (72.7%) of striatal cells are silent. Spontaneously active neurons, moreover, discharged at low rates (4.85 +/- 0.85 spikes/s). In separate experiments, both the AMPA/kainate (CNQX: 6-cyano-2,3-dihydroxy-7-nitro-quinoxaline disodium salt) and NMDA (AP5: D-(-)-2-amino-5-phosphonovaleric acid) GLU-receptor antagonists blocked the activity of most spontaneously active (83% CNQX, 69% AP5), and GLU-stimulated silent (68% CNQX, 98% AP5) units. Collectively, our results are consistent with an overall low level of striatal activity in the absence of strong excitatory input. When neuronal activity is initiated, however, it appears that both NMDA and AMPA/kainate receptors are critical for maintaining continuous impulse activity.

2-Amino-5-phosphonovalerate↗

PubMed2002

Modeling fast dopamine neurotransmission in the nucleus accumbens during behavior.

Recent advances in electrophysiology and voltammetry permit monitoring of dopamine (DA) neuronal activity in real time in the brain of awake animals. Studies using these approaches demonstrate that behaviorally relevant events elicit characteristic patterns of electrical activity in midbrain DA neurons as well as large, transient changes in extracellular DA in the nucleus accumbens (NAc). In addition to providing insight into the role of the DA system in the processing of motor, motivational, and sensory information, the new findings also shed light on fast DA neurotransmission in a behavioral context. This report, (1). summarizes the information obtained by electrophysiological and real-time voltammetric approaches and (2). describes a general model of phasic DA signaling in the NAc that links the observed changes in DA electrical activity and extracellular dynamics. The analysis demonstrates that the behaviorally evoked DA transients are governed by similar mechanisms as those produced by short trains of electrical stimulation. Thus, action potential-dependent release and presynaptic uptake are primary determinants of functional DA levels in the brain during behavior. Interestingly, the model predicts that the same burst of electrical activity generated at DA cell bodies produces markedly different DA dynamics in forebrain projection fields. The distinct changes result from heterogeneous release and uptake rates and may underlie region-specific effects of DA. Auto- and heteroreceptors, as well as other sites of presynaptic control, could further modulate the DA transients.

Animals↗

PubMed2002

Amphetamine inhibits behavior-related neuronal responses in substantia nigra pars reticulata of rats working for sucrose reinforcement.

Changes in activity of basal ganglia neurons, especially those in the striatum, are thought to underlie the characteristic behavioral patterns produced by d-amphetamine (AMPH). To study the role of the substantia nigra pars reticulata (SNr), a major basal ganglia output nucleus, we recorded from SNr neurons before and after a behaviorally activating dose of AMPH (0.5 mg/kg) in rats trained to nosepoke for sucrose reinforcement. Before AMPH, task-related behaviors were associated primarily with increases or both increases and decreases in SNr firing. Although these same behavior-related patterns persisted after AMPH, their relative magnitude was significantly attenuated. Units unresponsive during task events were unaffected by AMPH. Thus, rather than change the overall level of SNr firing, a behaviorally active dose of AMPH exerts context-dependent effects on the activity of SNr neurons.

Amphetamine↗

PubMed2002

Dysregulation of ascorbate release in the striatum of behaving mice expressing the Huntington's disease gene.

The extracellular fluid of the striatum contains a high level of ascorbate, an antioxidant vitamin known to play a key role in behavioral activation. We assessed the extracellular dynamics of ascorbate in R6/2 mice engineered to express the gene for Huntington's disease (HD), an autosomal dominant condition characterized by the loss of striatal neurons. Slow-scan voltammetry was used to measure striatal ascorbate during anesthesia and subsequent behavioral recovery. Although both the HD mice and their littermate controls had comparable ascorbate levels during anesthesia, the gradual return of behavioral activation over the next 120 min led to dramatically different ascorbate responses: a progressive increase in controls and a 25-50% decline in HD mice. In contrast, 3,4-dihydroxyphenylacetic acid, a major dopamine metabolite, showed no group differences. Behaviorally, HD mice were less active overall than controls and showed a relatively restricted range of spontaneous movements. Both the ascorbate and behavioral deficits were evident in 6-week-old HD mice and persisted in all subsequent test sessions through 10 weeks of age. Collectively, although these results are consistent with inadequate antioxidant protection in the HD striatum, they indicate that the ascorbate deficit is confined to periods of behavioral activation.

3,4-Dihydroxyphenylacetic Acid↗