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J M Tepper

Publications and source records attributed to J M Tepper.

49 records · Page 3Linked to original sources
PubMed1984

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of increases in impulse flow.

The effect of spontaneous and stimulation-induced alterations in impulse flow on the antidromic excitability of nigrostriatal dopaminergic neurons were investigated in urethane-anesthetized rats. Terminal excitability was found to be inversely related to the rate of spontaneous activity of nigral neurons. Conditioning stimulation applied to dopaminergic axons in the medial forebrain bundle was found to decrease terminal excitability, but axonal conditioning stimulation was without effect on antidromic responses evoked from the medial forebrain bundle. Decreases in terminal excitability induced by medial forebrain bundle stimulation could be blocked by local infusions of haloperidol into the region of the terminal fields, suggesting that the effect was receptor-mediated. These results are consistent with the proposal that nigrostriatal dopaminergic neurons may modulate the impulse-dependent release of dopamine from striatal nerve terminals as a function of firing rate by autoreceptor-mediated alterations in the electrical properties of the terminal membrane.

Animals↗
PubMed1984

Autoreceptor-mediated changes in dopaminergic terminal excitability: effects of striatal drug infusions.

The neurophysiological correlates of autoinhibition at the terminals of nigrostriatal dopaminergic neurons were studied by measuring the changes in antidromic excitability of nigrostriatal neurons following local infusions of various catecholamine agonists and antagonists into the neostriatum. Infusions of apomorphine or amphetamine reduced terminal excitability whereas the dopamine antagonists, haloperidol, fluphenazine or sulpiride, led to increases in terminal excitability. Alterations in antidromic excitability were constrained to the terminal regions and were not observed when infusions and excitability testing were performed in the medial forebrain bundle. The alpha-2 agonist, clonidine, did not alter dopaminergic terminal excitability. Our results indicate that pharmacological manipulations which have been shown to reduce the amount of stimulation-induced transmitter release from dopaminergic terminals are associated with a dopamine autoreceptor-mediated hyperpolarization and/or alteration in ionic conductance of the terminal membranes. These results are discussed with respect to mechanisms of autoinhibition in the central nervous system.

Animals↗
PubMed1982

Noradrenergic terminal excitability: effects of opioids.

The local infusion of morphine or D-Ala2, Met5-enkephalinamide into the frontal cortical terminal fields of noradrenergic neurons of the nucleus locus coeruleus resulted in a decrease in the excitability of the axon terminal regions to direct electrical stimulation. These effects were concentration dependent and could be blocked or partially reversed by the local infusion of naloxone. Some evidence was obtained for a differential antagonizing effect of naloxone upon the effects of morphine and D-Ala2, Met5-enkephalinamide. These results are discussed with respect to an effect of opioids on the polarization and/or ionic conductance of the terminal fields of locus coeruleus neurons, and to the possible regulation of neurotransmitter release by presynaptic opiate receptors.

Animals↗
PubMed1982

Changes in noradrenergic terminal excitability induced by amphetamine and their relation to impulse traffic.

The effects of amphetamine upon the terminal excitability of noradrenergic neurons of the nucleus locus coeruleus were studied in urethane anesthetized rats. Terminal excitability was measured by determining the stimulus currents necessary to evoke antidromic responses in locus coeruleus neurons from terminals in the frontal cortex. In most cases, terminal excitability was decreased following local infusion of amphetamine into the frontal cortex, while intravenous administration of the drug tended to increase terminal excitability. The decreased terminal excitability induced by local infusion of amphetamine appeared to be due to activation of alpha-adrenergic receptors located on the terminals of locus coeruleus neurons, since this effect mimics that of clonidine, a direct acting alpha-adrenergic agonist, and since the effect was abolished by pretreatment with alpha-methyl-p-tyrosine which disrupts the catecholamine liberating properties of amphetamine. Phentolamine, a direct acting alpha-adrenergic receptor antagonist was also found to block or reverse the effect of amphetamine. The changes in terminal excitability following intravenous injection of amphetamine appeared to be related to changes in the spontaneous activity of locus coeruleus neurons. A large decrease in spontaneous activity following intravenous administration of amphetamine was associated with increased terminal excitability, whereas when smaller changes in spontaneous activity occurred, terminal excitability was found to be decreased. These results are discussed with respect to the pharmacological properties of catecholaminergic neurons and the mechanisms of action of amphetamine.

Animals↗
PubMed1982

Subsensitivity of catecholaminergic neurons to direct acting agonists after single or repeated electroconvulsive shock.

Spontaneous firing rates and changes in firing rate in response to an intravenously administered dose of apomorphine were measured after various electroconvulsive shock (ECS) treatment regimens from dopaminergic cells of the substantia nigra in urethane-anesthetized rats. Similar measurements were obtained from noradrenergic neurons of the locus coeruleus before and after intravenous injection of clonidine. A significant decrement in the inhibition of spontaneous firing in response to intravenous administration of these agonists was observed following multiple or single ECS treatment in both substantia nigra and locus coeruleus cells. There was a consistent but nonsignificant tendency for cells in both areas of the brain from treated animals to display higher rates of spontaneous firing than their respective sham-shocked controls. Both the effects on base-line rates of spontaneous activity and on the depression of firing rate in response to drug administration were found to be independent of repeated treatment. A significant negative correlation was obtained between base-line firing rate and percentage depression to the autoreceptor agonist, but this correlation alone was insufficient to account for the observed differences in the drug response. These results are discussed with respect to possible mechanisms of action of electroconvulsive therapy in the treatment of depression.

Animals↗
PubMed1981

Neurophysiological consequences of presynaptic receptor activation: changes in noradrenergic terminal excitability.

Experiments were carried out to explore the view that activation of presynaptic receptors on the terminals of noradrenergic neurons is accompanied by alterations in their excitability to direct electrical stimulation. Antidromic action potentials evoked from frontal cortex of urethane anesthetized rats were recorded extracellularly from nucleus locus coeruleus. The threshold current necessary to evoke antidromic action potentials varied as a result of infusion of adrenergic agonists and antagonists into frontal cortex within 50 micrometer of the stimulating electrode. Local infusion of the alpha-adrenergic agonist clonidine produced a marked decrease in terminal excitability, while the alpha-antagonist phentolamine produced an increase in terminal excitability and was shown to reverse the effect of the agonist. Infusion of the beta-adrenergic agonist isoproterenol was without effect, although the beta-antagonist propranolol resulted in a decrease in terminal excitability. Infusions of potassium increased excitability of locus coeruleus terminals. Terminal excitability was seen to vary inversely with the rate of spontaneous or high frequency stimulation-induced firing of locus coeruleus neurons. From these observations, it may be inferred that activation or blockade of alpha-adrenergic presynaptic receptors results in changes in polarization and/or conductance of the noradrenergic synaptic endings. These results are discussed with respect to phenomena associated with the possible presynaptic regulation of neurotransmitter release.

Animals↗
PubMed1980

Acoustic priming and kanamycin-induced chochlear damage.

The cochleae from 3 lines of mice, selectively bred for differential susceptibility to priming-induced audiogenic seizures, were examined following acoustic priming and retest or kanamycin treatment, and the degree of cochlear damage was assessed. After 60 sec of acoustic priming, animals from the high and unselected lines which had subsequently developed audiogenic seizure susceptibility exhibited severe cochlear damage limited to the outer hair cells. Low line mice, which had been selected for resistance to acoustic priming-induced audiogenic seizures and were not seizure susceptible, exhibited no cochlear pathology following acoustic priming. Following kanamycin treatment, all 3 lines developed subsequent audiogenic seizure susceptibility. Histological examination of cochleae from mice so treated revealed a pattern of damage similar to that caused by acoustic priming, except that the cochleae of priming-induced audiogenic seizure resistant low line mice revealed a significant amount of outer hair cell damage. The results are discussed with respect to the physiological mechanism underlying a selectively bred behavioral phenotype in terms of a possible instance of damage/disuse-supersensitivity in the central nervous system.

Acoustic Stimulation↗
PubMed1979

Seizure proneness and neurotransmitter uptake.

The ability of midbrain homogenates from two strains of mice to accumulate several putative neurotransmitters, or their precursor in the case of acetylcholine, has been examined. The high-affinity transport mechanisms toward glutamate, GABA, dopamine, and glycine were similar in both strains. The seizure-prone DBA21BG strain had a significantly higher capacity to transport choline than did the relatively seizure-resistant C57BL/6 IBC mice. Howaver, no difference in the density of muscarinic binding sites in the two mouse strains was found.

Animals↗
PubMed1979

Relations between nicotine-induced convulsive behavior and blood and brain levels of nicotine as a function of sex and age in two inbred strains of mice.

Nicotine levels in blood and whole brain were measured as a function of sex and age in C57BL/6J and DBA/2J mice and compared to the behavioral responses following an intraperitoneal injection of nicotine. The results indicate that blood levels of nicotine alone do not accurately predict either brain levels of nicotine or the behavioral responses to a single injection of nicotine. In general, brain levels of nicotine proved to be a fairly accurate predictor of the behavioral responses to nicotine. The data indicate that the sexes differ in their sensitivity to nicotine. Forty-two-day-old male mice of both strains given comparable doses of nicotine were found to concentrate the drug in the brain more than females. However, there was no corresponding increase in sensitivity to this increased brain concentration as measured by LD50, ED50, latency to tremor or latency to death.

Aging↗
PubMed1976

Selective breeding for acoustic priming.

Data on eight generations of selective breeding for acoustic priming efficacy are reported. The realized heritability of this trait is approximately 0.2-0.3, indicating that the trait is determined in part by genetic factors. Animals selectively bred for acoustic priming do not differ in terms of first-trial (i.e., non-priming-induced) audiogenic seizures. These data suggest that acoustic priming and first-trial audiogenic seizures are controlled by different genetic mechanisms.

Acoustic Stimulation↗