Search PubMed⌕ Search

Biomedical subjects

G V Rebec

Publications and source records attributed to G V Rebec.

At least 91 records · Page 5Linked to original sources
PubMed1987

Dopaminergic neurons: simultaneous measurements of dopamine release and single-unit activity during stimulation of the medial forebrain bundle.

Simultaneous electrical and chemical recordings have been made of dopamine neuronal activity in the rat brain during electrical stimulation of the medial forebrain bundle. Tungsten recording electrodes were placed at the level of the substantia nigra and carbon-fiber, Nafion-coated, voltammetric electrodes were placed in the neostriatum. Dopamine units, verified by histology to be in the zona compacta of the substantia nigra, were identified by previously established electrophysiological criteria. Dopamine release was detected by fast-scan cyclic voltammetry, a technique which allows dopamine to be determined in vivo on a sub-second time scale. The majority of dopamine cells examined (7 out of 10) were antidromically activated by 60 Hz stimulation of the medial forebrain bundle. The same stimulus also elicits dopamine overflow in the caudate nucleus. Following stimulation, dopamine concentrations in the extracellular fluid of the neostriatum rapidly declined to prestimulus levels. In addition, impulse flow in dopaminergic neurons was inhibited for 20 s following stimulation. These measurements represent the first direct observation from a neuronal tract of simultaneous unit activity and chemical release of a neurotransmitter in real time.

Action Potentials↗
PubMed1987

Serotonergic dorsal raphe neurons: subsensitivity to amphetamine with long-term treatment.

Rats were pretreated twice daily for six consecutive days with either saline or 1.0, 5.0, or 10.0 mg/kg (+)-amphetamine. On the following day, single-unit recording techniques were used to identify serotonin-containing neurons in the dorsal raphe nucleus (DRN). Pretreatment with amphetamine did not alter the mean spontaneous firing rate of these cells, but in some instances it appeared to produce periods of irregular bursting. Moreover, the response to challenge injections of amphetamine was reduced significantly by pretreatment with the large dose. Thus, whereas an intravenous challenge of approximately 3.0 mg/kg produced a greater than 50% inhibition of activity in the dorsal raphe nucleus in rats pretreated with saline, 1.0 or 5.0 mg/kg (+)-amphetamine, more than twice the challenge dose was required to suppress the activity of serotonergic neurons in rats pretreated with 10.0 mg/kg (+)-amphetamine. These results parallel those previously obtained with dopaminergic neurons, suggesting that both types of cells lose their sensitivity to amphetamine with repeated injections.

Amphetamine↗
PubMed1986

Ipsapirone depresses neuronal activity in the dorsal raphe nucleus and the hippocampal formation.

Ipsapirone, a putative, novel anxiolytic with a high affinity for 5-HT1A binding sites, suppressed neuronal activity in both the dorsal raphe nucleus and hippocampal formation of urethane-anesthetized rats. In the hippocampus, dentate granule cells matched the responsiveness of dorsal raphe serotonin neurons, the median effective dose for 50% inhibition being 125.0 micrograms/kg in both areas. In contrast, the responses of CA1 pyramidal cells were related directly to baseline firing rates. Slow-firing neurons, for example, were inhibited by 31.3 micrograms/kg and fast-firing cells were unresponsive even up to a dose of 500.0 micrograms/kg. These results indicate a potent effect of ipsapirone on neuronal activity in sites with a high density of 5-HT1A receptors.

Animals↗
PubMed1986

Unilateral, intranigral infusions of amphetamine produce differential, bilateral changes in unit activity and extracellular levels of ascorbate in the neostriatum of the rat.

Simultaneous recordings of single-unit activity and oxidation current were obtained bilaterally from the neostriatum of rats in response to a unilateral infusion of D-amphetamine (2.0 microliters of 10 micrograms/microliter) into the substantia nigra. Whereas neuronal activity increases ipsilaterally and decreases contralaterally, the electrochemical signals, which reflect extracellular ascorbate, increase bilaterally. In each case, changes in unit activity precede the change in ascorbate release. Systemic administration of haloperidol (0.2 mg/kg) blocks the increase in oxidation current bilaterally, but reverses the neuronal activity response only on the ipsilateral side. These results lend further support to the view that intranigral amphetamine facilitates neostriatal ascorbate release, but this effect is not correlated with changes in single-unit activity.

Animals↗
PubMed1986

Crus cerebri lesions abolish amphetamine-induced ascorbate release in the rat neostriatum.

An increase in the concentration of ascorbate in the extracellular fluid of the rat striatum following systemic amphetamine administration previously has been demonstrated with the use of in vivo electrochemistry, push-pull cannula and in vivo dialysis. In this report, the effect of infusions of amphetamine into the substantia nigra on extracellular ascorbate levels in the striatum is further investigated by in vivo electrochemistry. Electrolytic lesions in the crus cerebri of the striatonigral pathway abolish this effect. Furthermore, these lesions abolish the effect of systemic amphetamine in the striatum ipsilateral to the lesion but not on the contralateral side. This phenomenon is independent of neostriatal dopamine or gamma-aminobutyric acid since levels were shown to be unchanged relative to the intact side. These results lend further support to the hypothesis that ascorbate secretion in the striatum after amphetamine is mediated in the central nervous system, and indicate that a pathway that courses through the crus cerebri is necessary for this release.

Amphetamine↗
PubMed1986

Multiple amphetamine injections reduce the release of ascorbic acid in the neostriatum of the rat.

Voltammetric signals were recorded bilaterally with unmodified or electrochemically-modified carbon-fiber electrodes in the neostriatum of rats that sustained a unilateral depletion of dopamine by pretreatment with 6-hydroxydopamine. In both hemispheres, single daily injections of D-amphetamine (5.0 mg/kg or steadily increasing doses beginning with 6.0 mg/kg) for 6 consecutive days significantly reduced the rise in oxidation current produced by a challenge injection of 2.5 mg/kg D-amphetamine compared to the response obtained from saline-treated controls. Voltammetric scans indicated that the oxidized substance shared the electrochemical characteristics of ascorbic acid. It appears, therefore, that multiple amphetamine injections reduce the release of ascorbic acid in the neostriatum and that this effect does not depend on the integrity of dopaminergic neurons.

Amphetamine↗
PubMed1986

Differential response of amygdaloid neurons to clozapine and haloperidol: effects of repeated administration.

Rats were pretreated with saline or with behaviorally equivalent doses of clozapine (10.0 mg/kg) or haloperidol (1.0 mg/kg) twice daily for six consecutive days. On the following day, amygdaloid neurons in clozapine-pretreated rats responded to a challenge injection of this drug with a significantly greater increase in firing rate than saline controls. In contrast, amygdaloid neurons generally remained unresponsive to haloperidol even when pretreatment with this drug was extended to 13 days. Neither clozapine nor haloperidol pretreatment, however, altered the response of amygdaloid neurons to d-amphetamine administered after a four-day washout period. Amphetamine inhibited amygdaloid activity to a comparable extent in all rats. Taken together, these results implicate the amygdaloid complex as an important site of action of clozapine and related antischizophrenic drugs.

Amygdala↗
PubMed1985

Modulation of neostriatal activity by iontophoresis of ascorbic acid.

Iontophoresis (20-80 nA) of ascorbic acid (AA) accelerated the firing rate of approximately one-third of the neurons tested in the anteromedial neostriatum of anesthetized rats. When administered to neostriatal neurons that were activated by the simultaneous ejection of glutamic acid (GLU), AA excited more than two-thirds of the cells examined, including many that were not excited by AA alone. At ejection currents above 80 nA, AA further increased the activity of some GLU-activated neurons, but suppressed the firing rate of others. Electrochemical quantification of AA ejection during iontophoresis indicated that the concentration of AA at the tip of the recording electrode was within reasonable physiological limits. It is concluded that endogenous AA may modulate neuronal activity in the neostriatum.

Animals↗
PubMed1985

Nigral reticulata neurons: potentiation of responsiveness to amphetamine with long-term treatment.

Single-unit activity was recorded in the substantia nigra pars reticulata of rats in response to intravenous challenge injections of D-amphetamine. The animals were pretreated with saline or 5.0 mg/kg D-amphetamine twice daily for 6 consecutive days. Whereas the large majority of saline controls (6 of 8) showed no consistent responses to amphetamine at doses up to 2.0 mg/kg, amphetamine pretreated rats (7 of 10) responded with a progressive increase in firing rate. Both groups of animals responded to a subsequent injection of 5.0 mg/kg clozapine with a depression of firing rate. The remaining control rats were inhibited by amphetamine and this aberrant response was enhanced with long-term treatment. In these unusual cells, clozapine accelerated firing rate. Taken together, these results indicate that unlike dopaminergic neurons in the compacta region of the nigra, reticulata neurons increase their responsiveness to amphetamine with repeated administration.

Animals↗
PubMed1985

Ascorbic acid and the behavioral response to haloperidol: implications for the action of antipsychotic drugs.

Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs.

Animals↗
PubMed1985

Unilateral dopamine depletions attenuate the response of striatal neurons to systemic amphetamine in both hemispheres.

Neuronal activity was recorded bilaterally from the striatum of intact control animals and rats pretreated 10-15 days earlier with a unilateral intranigral injection of 6-hydroxydopamine. Following isolation of single unit discharges, each group was challenged with intravenous injections of 0.2 mg kg-1 d-amphetamine administered at 2-min intervals. Striatal neurons from intact control animals responded to amphetamine with equal numbers of inhibitions and excitations. In contrast, the predominant response in the animals with lesions was no response at all even with a total cumulative dose of 2.0 mg kg-1. Approximately 50% of the neurons in each striatum of the rats with unilateral lesions failed to respond to amphetamine despite a greater than 98% difference in dopamine levels between hemispheres. The remaining neurons in these animals responded as in intact controls. These results suggest that some functional change occurs following unilateral dopamine depletion that acts to decrease the response of neurons to amphetamine in both the intact and the dopamine-depleted striatum.

Animals↗
PubMed1984

Iontophoretic evidence for subsensitivity of postsynaptic dopamine receptors following long-term amphetamine administration.

Neuronal activity was recorded from the anteromedial neostriatum of rats pretreated twice daily for 6 consecutive days with saline or 5.0 mg/kg d-amphetamine. Glutamate was applied in both groups of animals to increase spontaneous firing rates. Iontophoretic application of increasing currents of DA (20-120 nA) produced a progressive inhibition of unit activity in control animals that was significantly reduced in rats pretreated with amphetamine. These results support the view that long-term amphetamine treatment reduces the sensitivity of postsynaptic DA receptors in the neostriatum.

Animals↗
PubMed1984

Nigral dopaminergic neurons: differential sensitivity to apomorphine following long-term treatment with low and high doses of amphetamine.

Twice daily injections of 1.0 or 5.0 mg/kg D-amphetamine for 6 consecutive days differentially affected the response of dopaminergic neurons in the substantia nigra pars compacta to challenge injections of apomorphine on the following day. Thus, whereas treatment with the high amphetamine dose produced a dramatic shift to the right of the apomorphine dose-response curve, rats treated with 1.0 mg/kg D-amphetamine responded to apomorphine in the same way as saline-treated controls. These results support the view that long-term treatment with relatively high amphetamine doses is required to produce autoreceptor subsensitivity in the substantia nigra.

Animals↗
PubMed1984

Long-term amphetamine treatment attenuates or reverses the depression of neuronal activity produced by dopamine agonists in the ventral tegmental area.

Neuronal activity was recorded from the ventral tegmental area (VTA) of immobilized, locally anesthetized rats on the day immediately following long-term treatment (twice daily for 6 consecutive days) with saline, 1.0 or 5.0 mg/kg d-amphetamine (d-AMPH). Each rat was challenged intravenously with d-AMPH (beginning with 0.0625 mg/kg) or with 0.005 mg/kg apomorphine. Treatment with d-AMPH significantly reduced the ability of this drug to inhibit VTA activity. In fact, nearly half of the neurons in the high-dose treatment group were excited by d-AMPH, whereas only 20% of control neurons showed this response. Moreover, apomorphine routinely accelerated firing rate in the VTA following treatment with 5.0 mg/kg d-AMPH but this response was never observed in control neurons, not even in those that were excited by d-AMPH. Thus, tolerance appears to develop to the ability of dopamine agonists to inhibit VTA activity and this effect may be mediated, at least in part, by a subsensitivity of inhibitory dopamine autoreceptors.

Action Potentials↗
PubMed1984

Apomorphine-induced inhibition of neostriatal activity is enhanced by lesions induced by 6-hydroxydopamine but not by long-term administration of amphetamine.

Single-unit activity was recorded in the neostriatum of locally-anesthetized, immobilized rats which had received either a unilateral injection of 6-hydroxydopamine (6-OHDA) into the nigro-neostriatal dopamine pathway, or repeated injections (twice daily for 6 days) of saline, 1.0, 5.0 or 10.0 mg/kg (+)-amphetamine. A staircase regimen of apomorphine was administered intravenously to each rat to determine if the long-term administration of amphetamine changed the sensitivity of postsynaptic dopamine receptors in a way comparable to that produced by 6-hydroxydopamine. In all groups, the most frequent response to apomorphine was inhibition of neostriatal activity. In saline-treated rats, most units were moderately excited by small doses of apomorphine (0.0025-0.02 mg/kg) and then inhibited by doses exceeding 0.04 mg/kg. In rats with lesions induced by 6-hydroxydopamine, apomorphine caused significantly more inhibition than in saline-treated animals. By contrast, neuronal responses in amphetamine-treated rats were not significantly different from those of saline controls. These results indicate that the long-term administration of amphetamine produces an augmentation of behavior by some mechanism other than an increase in the sensitivity of postsynaptic dopamine receptors.

Action Potentials↗
PubMed1984

Critical issues in assessing the behavioral effects of amphetamine.

Amphetamine induces a behavioral syndrome in mammals that includes a variety of repetitive behaviors. An integral component of this syndrome in humans is the presence of a thought disturbance not unlike that manifest in idiopathic paranoid schizophrenia. The consistent pattern of behavioral changes produced by amphetamine across species, when considered in light of the psychosis it elicits in humans, has suggested to many that these drug-induced changes in animals may provide a model of the endogenous psychosis in humans. Amphetamine-induced changes in open-field behavior in the rat have been the most widely studied in attempts to formulate a model for investigating the neurobiological mechanisms underlying amphetamine psychosis and paranoid schizophrenia in humans and for testing the therapeutic efficacy of new antipsychotic drugs. The procedures used to assess the behavioral response to amphetamine, however, typically include rating scales or automated recordings that by their very nature ignore those components of the behavioral response that may be most critical for developing a viable animal model of the naturally occurring psychosis. Further, open-field behavior is often recorded during arbitrarily selected intervals without consideration for the multiphasic nature of the entire amphetamine response. We discuss how incomplete descriptive analyses of the amphetamine behavioral response in rats has led to confusion in the literature and describe behavioral research that is paradigmatic of the work we believe is most likely to eventuate in significant progress in the field.

Amphetamine↗