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H C Moises

Publications and source records attributed to H C Moises.

At least 55 records · Page 3Linked to original sources
PubMed1985

The monoaminergic innervation of the rat visual cortex.

The intracortical distribution of monoamines, noradrenaline (NA) and serotonin (5-HT), was examined in the visual cortex of the rat with high pressure liquid chromatography (h.p.l.c.) and radioautography. H.p.l.c. measurements showed the densities of both amines to be highest in layer I. The concentration of NA varied considerably in all other layers while the 5-HT concentration decreased with increasing distance from the pial surface. The morphological characteristics of the monoaminergic axon-terminals in the cerebral cortex has been the subject of controversy in recent years. We have used radioautography following topical or intraventricular administration of tritiated amines to examine the ultrastructural features of these terminals in the visual cortex of the rat. Systematic analysis of single sections revealed that more than one-half of the terminals labelled with tritiated NA or 5-HT formed typical synaptic contacts (mostly type I) with dendritic shafts or spines.

Animals↗
PubMed1985

Electrophysiological effects of dynorphin peptides on hippocampal pyramidal cells in rat.

Single-unit extracellular recording was carried out in rats to characterize the effects of dynorphin and several structurally related peptides on hippocampal pyramidal cell activity. Dynorphin, applied electrophoretically or by pneumatic pressure, produced a dose-dependent depression of both spontaneous and glutamate-evoked discharge in a majority (63%) of CA1 and CA3 cells tested. In addition, a small number of cells in both cellular fields responded to the peptide with a prolonged elevation in firing. The inhibitory effects of dynorphin were not blocked by naloxone. Moreover, administration of des-tyrosine-dynorphin depressed the firing of pyramidal cells in a manner similar to that of the parent compound. Ethylketocyclazocine produced a mixed pattern of excitatory and inhibitory effects, whereas naloxone-sensitive elevations in firing were most often observed with the application of dynorphin-(1-8). Application of [Leu5]enkephalin produced only facilitations in pyramidal cell firing. The possibility is raised that biologically significant non-opiate actions, in addition to potent opiate-mediated effects, may occur upon release of pro-dynorphin peptides in the hippocampus.

Animals↗
PubMed1985

A review of some nonopioid actions of dynorphin.

The evidence for several sites of activity within the dynorphin sequence is reviewed. A number of endocrine and CNS peptides are believed to contain several sites of biological activity. Data from a number of laboratories is consistent with such a mechanism for the opioid peptide dynorphin. These findings stem from structure-activity studies in which nonopiate fragments of dynorphin sometimes show biological activity and from the failure of naloxone to reverse some effects of dynorphin. These results are discussed in terms of the possible physiological relevance of such nonopiate actions.

Animals↗
PubMed1984

Changes occur in central adrenoreceptor function following long-term morphine treatment and during morphine withdrawal.

Radioligand binding techniques were used in combination with in vivo electrophysiological recording to characterize changes in beta adrenoreceptor activity in various brain areas in rats treated chronically with morphine. Following chronic morphine treatment, the maximum number of specific binding sites for 3H-dihydroalprenolol (3H-DHA) in parietal cortex and hippocampus showed a biphasic change, indicating an initial increase and decrease (relative to controls) in beta adrenoreceptors in these regions with time during withdrawal. No appreciable changes were observed in the dissociation constants for 3H-DHA binding. The changes in cortical beta adrenoreceptor density found in early (8 hr) and later phases (32 hr) of withdrawal were paralleled by a selective increase and decrease, respectively, in cortical neuron sensitivity to noradrenergic stimulation. These results suggest a possible linkage between changes in central adrenoreceptor function and the formation and/or expression of opiate dependence.

Adrenergic beta-Agonists↗
PubMed1984

Comparison of norepinephrine- and benzodiazepine-induced augmentation of Purkinje cell responses to gamma-aminobutyric acid (GABA).

The hypothesis tested in the present study was that the benzodiazepines (i.e., flurazepam) and norepinephrine (NE) share a common mechanism to facilitate cerebellar Purkinje neuron responsiveness to iontophoretically applied gamma-aminobutyric acid (GABA). Extracellular activity was recorded from Purkinje neurons in halothane-anesthetized rats from each of the following groups: 1) naive, 2) acute or chronic flurazepam treated, 3) chronic desmethylimipramine treated and 4) injected with 6-hydroxydopamine. Single unit responses to pulsatile (10 sec duration at 45-sec intervals) iontophoretic administration of GABA were examined before, during and after NE or flurazepam microiontophoresis in all treatment groups. Drug response histograms were generated and used to quantitate NE and flurazepam effects on spontaneous activity and GABA-induced inhibitory responses. Doses of GABA sufficient to produce depression of Purkinje cell activity in naive rats (4-40 nA) suppressed firing rate in all Purkinje cells tested in drug-treated animals. In contrast to its consistent GABA facilitating action in naive controls, iontophoretically applied flurazepam was ineffective in augmenting GABA-induced suppression of Purkinje cell discharge in acute and chronic flurazepam-treated animals. Although GABA facilitation by NE was unaffected by acute systemic administration of a benzodiazepine, chronic treatment with flurazepam produced a subsensitivity to the noradrenergic GABA facilitating effects. Within 48 hr of withdrawal from chronic benzodiazepine treatment, both NE and flurazepam again enhanced GABA-induced suppression of Purkinje cell discharge routinely. Chronic desmethylimipramine treatment as well as iontophoresis of the blocking agents sotalol and fluphenazine which have been shown previously to block or reduce NE-mediated enhancement of GABA actions were ineffective in altering the facilitating effect of flurazepam on GABA. Likewise, 6-hydroxydopamine pretreatment had no effect on GABA augmentation by flurazepam. Thus, although flurazepam appears to act independently from the noradrenergic receptor system in augmenting GABA-induced depression of Purkinje cell discharge, a reversible subsensitivity to the GABA facilitating effects of both flurazepam and NE can be produced by chronic treatment with this benzodiazepine. On the basis of this "cross-subsensitivity" to NE and flurazepam actions, it seems reasonable to suggest that these two agents might enhance GABA inhibitory actions by a common biophysical mechanism subsequent to noradrenergic receptor activation.

Animals↗
PubMed1983

Changes in alpha2 adrenoreceptors in various areas of the rat brain after long-term administration of "mu" and "kappa" opiate agonists.

Clonidine, an alpha 2 adrenoreceptor agonist, is used to treat opiate dependent individuals who are experiencing the signs and symptoms of withdrawal. Changes in the apparent number of alpha 2 adrenoreceptors in specific areas of the rat brain have been observed after chronic morphine administration. In the present study, the effects of chronically administered morphine sulfate upon alpha 2 adrenoreceptors were compared to those of UM-1072, (+/-)-5,9-alpha-dimethyl-2-hydroxy-2-tetrahydro-furfuryl-6, 7-benzomorphan HCl, a "kappa" agonist which does not produce typical morphine-like dependence. The maximum number of specific binding sites (Bmax) and dissociation constants (KD's) for 3H-clonidine were measured with neural membranes isolated from saline or drug-treated rats. Rats were injected with saline, morphine or UM-1072, i.p., every 8 hr for 14 days. Doses of morphine ranged from 10 mg/kg, t.i.d., on the first three days to 100 mg/kg, t.i.d., on the last two days. Doses of UM-1072 covered a similar range. In control experiments, the Bmax's for specific binding of 3H-clonidine were (in fmoles/mg protein): hypothalamus, 142 +/- 7; amygdala, 141 +/- 3; brainstem, 70 +/- 2; parietal cortex, 130 +/- 4; hippocampus, 94 +/- 2; and caudate nucleus, 62 +/- 3. After chronic morphine treatment, the Bmax's were decreased significantly in all areas except the hippocampus. After chronic UM-1072 treatment, the Bmax's were decreased significantly in all areas studied. Neither treatment altered appreciably the KD's for 3H- clonidine. This study suggests that "mu" and "kappa" agonists might have similar actions upon noradrenergic systems in the brain.

Animals↗
PubMed1983

Locus coeruleus stimulation potentiates local inhibitory processes in rat cerebellum.

We previously reported that a low threshold action of norepinephrine (NE) on the cerebellar circuitry is expressed as an amplification of the inhibitory action of gamma aminobutyric acid (GABA) on Purkinje cell activity. Here we examined the effects of locus coeruleus (LC) stimulation on "off-beam" inhibitions of Purkinje cell firing induced by activation of local basket and stellate cell interneurons to determine whether endogenous NE, released from synaptic terminals, could induce a comparable enhancement of GABA-mediated synaptic input to these neurons. Stimulation of LC, at current intensities which by themselves were subthreshold for directly affecting background activity of Purkinje neurons, markedly increased off-beam inhibitory neuronal responses. Iontophoretic application of the beta-adrenergic blocker sotalol reversibly antagonized this enhancement of synaptic inhibition. In comparison, the potentiative effects observed with LC stimulation were increased by iontophoresis of the alpha-adrenergic blocker phentolamine. LC -induced increases in off-beam inhibition were not observed after destruction of cerebellar noradrenergic terminals by 6-hydroxydopamine. These results suggest that noradrenergic input from the LC can augment the efficacy of conventional GABA-mediated inputs synapsing on the Purkinje cell.

Animals↗
PubMed1982

Nonopiate effects of dynorphin and des-Tyr-dynorphin.

Intracerebroventricular administration of dynorphin produced potent and long-lasting effects on motor function and the electroencephalogram in rats. In addition, local iontophoretic or pressure ejection of dynorphin consistently inhibited hippocampal unit activity. None of these effects were significantly affected by naloxone even at high doses. Moreover, a fragment of dynorphin that failed to displace any of a number of tritiated narcotics from rat brain homogenates produced similar effects on these physiological measures in vivo. On the basis of a variety of criteria for "opiate action," the results suggest that a second biologically active site within the dynorphin sequence is capable of quite potent but nonopiate effects.

Action Potentials↗
PubMed1981

Locus coeruleus stimulation potentiates Purkinje cell responses to afferent input: the climbing fiber system.

In cerebellum, the evoked responses of the Purkinje cell to both excitatory and inhibitory afferent input have previously been shown to be enhanced by local iontophoresis of norepinephrine (NE). The influence of locus coeruleus (LC) conditioning stimulation on Purkinje cell responses to climbing fiber input was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar potentiative effects. Stimulation of LC, at intensities which by themselves were subthreshold for directly affecting background activity, markedly enhanced complex spike excitation of Purkinje cells elicited by activation of climbing fiber inputs from sensorimotor cortex. Depressant responses observed after complex spike excitation were also augmented by the LC conditioning. Iontophoretic application of sotalol, a specific beta-adrenergic receptor blocker, reversibly antagonized this facilitation of climbing fiber-evoked responses. In addition, the potentiative effects of LC stimulation were not observed after destruction of NE-containing axons and terminals in cerebellum by 6-OHDA. These results suggest that noradrenergic input from the LC can enhance the efficacy of climbing fiber synaptic action on the Purkinje cell, and are thus consistent with the hypothesis of a 'modulatory' role rather than a specific information transfer function for NE in cerebellum.

Afferent Pathways↗
PubMed1980

Potentiation of GABA inhibitory action in cerebrllum by locus coeruleus stimulation.

In cerebellum, excitatory and inhibitory responses of Purkinje cells, produced both synaptically and by microiontophoresis of putative amino acid neurotransmitters, have been shown previously to be enhanced during NE iontophoresis. The influence of locus coeruleus conditioning stimulation on Purkinje cell responses to GABA iontophoresis was examined to determine whether endogenous NE, released from synaptic terminals, could exert similar modulatory effects. Locus coeruleus stimulation at current intensities which alone elicited no direct depression of Purkinje cell spontaneous discharge potentiated the inhibition produced by GABA. Iontophoretic application of sotalol, a specific beta-adrenergic blocker, antagonized this enhancement of GABA inhibition. Repetitive activation of the classic non-adrenergic cerebellar afferents did not enhance the GABA response, despite causing a direct depression in spontaneous rate. A neuromodulatory role is suggested for tonic adrenergic input in the mammalian central nervous system.

Afferent Pathways↗
PubMed1980

GABA facilitation by noradrenaline shows supersensitivity in cerebellum after 6-hydroxydopamine.

Alterations of cerebellar Purkinje cell responses to microiontophoretically applied noradrenaline (NA) were studied in rats after the destruction of NA-containing afferents and terminals by 6-hydroxydopamine (6-OHDA). An enhanced efficacy of NA action after 6-OHDA treatment was indicated by a significant reduction in the mean iontophoretic current required for a threshold depressant response to NA. A potentiation of gamma aminobutyric acid (GABA)-mediated inhibition by administration of NA, similar to that previously observed in control animals, was also reliably elicited in 6-OHDA pretreated rats. In addition, Purkinje cells appeared to demonstrate an increase in sensitivity to such facilitating actions of NA, defined here as "modulatory supersensitivity". In contrast to the prolonged synergistic interactions between NA and GABA observed in control animals, however, the enhancement of the amino acid response in 6-OHDA treated animals did not persist beyond the period of NA ejection and converted instead to a period of rebound insensitivity to GABA action. These results provide electrophysiological evidence for the emergence of supersensitivity to NA action in cerebellum after the loss of noradrenergic input from locus coeruleus.

Animals↗
PubMed1979

Modulatory actions of norepinephrine in the central nervous system.

Early studies have shown that norepinephrine (NE) released synaptically or iontophoretically onto neurons in the central nervous system acts to depress firing by a mechanism associated with a hyperpolarization but no change or an increase in membrane resistance. This in contrast to classical transmitters, which cause hyperpolarization by a conductance increase. Recent studies designed to clarify the functional implications of these biophysical actions have revealed new phenomenons in which the major overall effect of NE on cerebellar Purkinje cells is to enhance conventional synaptic input and induce an increase in signal-to-noise ratio of evoked versus spontaneous activity. NE released iontophoretically or via stimulation of the locus coeruleus also has been found to enhance the inhibitory effects of gamma-aminobutyric acid, an endogenous cerebellar transmitter. The effects appear even at low doses of NE having no direct depressant action on spontaneous activity. Specificity tests have shown no enhancement of glycine-induced inhibition by NE and an inability of dopamine to mimic NE. The hypothesis is presented that a significant action of NE in the central nervous system is to induce a bias that alters postsynaptic responsiveness to conventional transmitter systems, which themselves may be more directly concerned with detailed information transfer.

Animals↗