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Biomedical subjects

B J Hoffer

Publications and source records attributed to B J Hoffer.

At least 163 records · Page 9Linked to original sources
PubMed1980

Catecholamine modulation of enkephalin-induced electrophysiological responses in cerebral cortex.

The interaction between locally applied D-Ala2-methionine enkephalinamide (2dA) and catecholamine inputs to frontal cortex was investigated in rats. Parenteral administration of antipsychotic agents known to block catecholamines receptors, such as spiroperidol, alpha-flupenthixol and (+)-butaclamol, reversibly antagonized enkephalin-induced depressions. The biochemically inactive isomers of these antipsychotics, beta-flupenthixol and (-)-butaclamol, manifested no such activity. Unilateral lesions of the catecholaminergic projections to frontal cortex, produced by interstitial injection of 6-hydroxydopamine, resulted in an ipsilateral decrease in 2dA efficacy and in an elimination of the antagonisms of 2dA depressions by antipsychotic agents. The depressions caused by 2dA were not antagonized by iontophoretically applied Mg++. It is concluded that intact catecholaminergic transmission is required for the full expression of enkephalin-induced depressions in frontal cortex and that this mechanism probably does not involve presynaptic release. Taken together with other recently published data, these results suggest that catecholamines may act as postsynaptic modulators to augment responsiveness to enkephalins.

Action Potentials↗
PubMed1980

Electrophysiological actions of benzodiazepines.

Electrophysiological investigations have revealed that benzodiazepines, applied either locally or systemically, reduce central nervous system excitability. The studies summarized here indicate that this depression of excitability by benzodiazepines is a result of an increase in gamma-aminobutyric acid (GABA) mediated inhibition. This increase in inhibition may result from benzodiazepines increasing the activity of some GABAergic neurons and also from a modulatory action of benzodiazepines on GABA actions at some postsynaptic receptor sites. The modulatory action is observed with doses of benzodiazepines that do not cause any direct effects on neuronal excitability or membrane polarization. Specificity tests indicate that benzodiazepines do not enhance inhibition mediated by glycine or monoamines such as norepinephrine or serotonin. Results of experiments with a convulsant benzodiazepine compound, which causes a specific reduction in GABA-mediated inhibition, are also presented, The data are discussed in terms of a model in which the benzodiazepine receptor, the GABA receptor, and the chloride ionophore are functionally linked. Furthermore, it is proposed that some postsynaptic actions of GABA may be continually regulated by the occupancy of a benzodiazepine receptor, and that occupancy of the benzodiazepine receptor may be permissive for the GABA-elicited increase in chloride ion permeability.

Benzodiazepines↗
PubMed1980

Electrophysiological evidence for presynaptic actions of phencyclidine on noradrenergic transmission in rat cerebellum.

The actions of the psychotomimetic drug phencyclidine (PCP) were studied using Purkinje neurons in the cerebellum of urethane-anesthetized rats. PCP, applied by micropressure ejection through multibarreled micropipettes, depressed the spontaneous activity of these neurons as recorded by extracellular electrophysiological techniques. This depressant effect was blocked by neuroleptic drugs and lithium, both of which also block the depressant effects of norepinephrine, but not those of gamma-aminobutyric acid. PCP-elicited depressions could not be obtained in rats in which the cerebellar noradrenergic terminals had been lesioned selectively by pretreatment with the neurotoxin 6-hydroxydopamine. However, PCP was still an effective depressant in animals after destruction of non-noradrenergic intrinsic excitatory and inhibitory interneurons which synapse on the Purkinje cell by neonatal X-irradiation. Further treatment of the X-irradiated animal with 6-hydroxy-dopamine resulted in Purkinje neurons which were not responsive to PCP. Administration of magnesium ions, which reduces the release of neurotransmitters from afferent terminals, also blocked the depressant effects of PCP. The results of this study suggest that PCP acts in the cerebellum by a presynaptic mechanism involving the release of norepinephrine from intact, functioning noradrenergic terminals.

Animals↗
PubMed1979

Brain grafts reduce motor abnormalities produced by destruction of nigrostriatal dopamine system.

In order to determine if brain tissue grafts can provide functional input to recipient central nervous system tissue, fetal rat dopamine-containg neurons were implanted adjacent to the caudate nucleus of adult recipients whose endogenous dopaminergic input had been destroyed. The grafts showed good survival and axonal outgrowth. Motor abnormalities, which had been induced by the destruction of the endogenous dopaminergic input to the caudate, were significantly reduced after grafting of the fetal brain tissue. These data suggest that such implants may be potentially useful in reversing deficits after circumscribed destruction of brain tissue.

Animals↗
PubMed1979

Seizures and related epileptiform activity in hippocampus transplanted to the anterior chamber of the eye: modulation by cholinergic and adrenergic input.

Transplants of rat hippocampus into the anterior chamber of the eye of a host animal were used to assess the effects of cholinergic and adrenergic neuronal inputs on the generation and duration of seizure activity. Cholinomimetics initiated both seizures and hypersynchronous neuronal activity in the transplants. Cyclic guanosine monophosphate (GMP) derivatives and isobutyl methylxanthine elicited similar changes. Reflex activation of the cholinergic parasympathetic input to the iris and transplant by illumination of the ipsilateral retina also induced seizures or increased the rate of penicillin-induced interictal spike discharge. Application of beta-adrenergic agonists inhibited interictal spikes and paroxysmal depolarizing shifts induced by penicillin. Fluorescence histochemical studies showed that host sympathetic adrenergic fibers derived from the ground plexus of the iris invaded the transplant to form fine varicose nerve terminals. Activation of these adrenergic afferents to the transplant diminished both the amplitude and frequency of penicillin-induced epileptiform activity. Epileptiform activity in hippocampal occular transplants is strongly modulated by cholinergic and adrenergic neuronal inputs, with the former exerting a facilatory influence and the latter, an inhibitory effect.

Adrenergic Fibers↗
PubMed1979

Interaction of diazepam with synaptic transmission in the in vitro rat hippocampus.

Diazepam (5 x 10(-8) - 10(-6) M) was found to augment recurrent inhibition of pyramidal neuron firing in a dose-dependent manner in rat hippocampal slices. To determine possible loci of this effect, diazepam was locally administered by pressure ejection from a micropipette, while recording action potentials from single inhibitory ("basket") interneurons. Diazepam induced reversible and reliable increases in interneuron firing in response to stimulation of Schaffer collateral and commissural afferents. Taken together with previous electrophysiological reports, these data suggest that benzodiazepines may augment central inhibition by increasing either the excitability of inhibitory interneurons, or by increasing the strength of excitatory afferents to these cells.

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↗
PubMed1978

Benzodiazepines and central inhibitory mechanisms.

The effect of diazepam was evaluated on spontaneous activity and drug- and electrically-elicited inhibitions of neuronal activity. Doses of diazepam which did not change spontaneous firing rates markedly enhanced GABA-mediated inhibitions in rat cerebellum in situ and in tissue cultures of rat hypothalamus. The effects of diazepam were readily reversible, and could be antagonized by picrotoxin; no effect on glycine or norepinephrine-induced inhibition was seen. It is concluded that actions of diazepam are mediated, at least in part, by a specific increase in GABA-mediated inhibition in the central nervous system.

Animals↗
PubMed1978

A gated, high voltage iontophoresis system with accurate current monitoring.

A circuit description for a multichannel constant current source for microiontophoresis is presented. The circuitry allows a high voltage compliance, accurate monitoring of ionotophoretic current without use of batteries, and automatic current neutralization. Drugs may be applied either manually or with an external digital gate signal. A monitor to detect current unbalance greater than a preselected level is also included.

Iontophoresis↗
PubMed1977

Effect of calcium removal on monoamine-elicited depressions of cultured tuberal neurons.

The role of extracellular calcium in monoamine responses of central neurons was ivestigated using explant cultures of tuberal hypothalamus. The spontaneous activity of neurons in cultures was recorded in balanced salt and calcium-deficient salt solutions. This increased firing rate was counteracted by the addition of magnesium. Addition of magnesium also regularized the pattern of firing. Iontophoretic application of putative monoamine neurotransmitters reversibly decreased the rate of firing in both normal and calcium-deficient salt solutions. These results suggests that monoamine inhibitions are not primarily mediated by transmembrane calcium fluxes.

Action Potentials↗