PubMed Health⌕ Search

Biomedical subjects

R J Reiffenstein

Publications and source records attributed to R J Reiffenstein.

At least 37 records · Page 2Linked to original sources
PubMed1987

Interaction between flurazepam and ethanol.

The interaction of a representative benzodiazepine, flurazepam, and ethanol has been assessed in ICR albino mice. Tests done included loss of "rotarod" performance, light sedation, deep sedation, loss of righting reflex, anesthesia, and lethality. LD50 and ED50s were plotted as isobolograms (plots of equieffective dose combinations). Data for anaesthesia and lethality showed little or no interaction between the two drugs. In contrast, the four motor and behaviour tests showed synergism, especially with higher doses of ethanol (over 2 g/kg) for righting reflex, and (over 1.5 g/kg) for deep sedation. Synergism occurred over all doses for light sedation and rotarod performance. It is expected that concurrent use of benzodiazepines and ethanol can result in a significantly higher accident risk in humans, but little additional risk of death from simple overdose.

Anesthesia↗
PubMed1986

Direct comparison of hallucinogenic phenethylamines and D-amphetamine on dorsal raphe neurons.

We compared the effects of the hallucinogens 2,5-dimethoxy-4-methylamphetamine (DOM), mescaline and the simulant D-amphetamine, applied by microiontophoresis to rat dorsal raphe (DR) units. DR neuron firing rate was relatively insensitive to DOM and unaffected by mescaline, but was clearly inhibited by D-amphetamine. Intravenous DOM usually inhibited, but this effect was correlated with blood pressure changes; i.v. D-amphetamine produced inconsistent responses. These results suggest that most of the effects seen on i.v. administration of phenethylamines are not mediated directly on the serotonergic cell.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1986

Possible involvement of serotonin receptors in the facilitatory effect of a hallucinogenic phenethylamine on single facial motoneurons.

2,5-Dimethoxy-4-methylamphetamine (DOM, "STP") is a potent hallucinogen, proposed to be a serotonin receptor agonist. Its effects have not previously been tested upon central neurons where serotonin is excitatory and serotonin antagonists are effective. Extracellular single unit recordings were obtained from facial motoneurons in anaesthetized rats, and drugs were applied from five-barrelled micropipettes by iontophoresis. Facial motoneurons were commonly silent. During subthreshold application of glutamate, firing could be induced by dopamine and DOM. As reported by others, serotonin and noradrenaline also excited facial motoneurons under these conditions. Methysergide antagonized responses to serotonin and DOM but not those to noradrenaline; methysergide could not usually discriminate between responses to serotonin and dopamine. Ketanserin reversibly antagonized (but could not discriminate between) responses to serotonin, dopamine, and noradrenaline. Chlorpromazine antagonized responses to dopamine at doses that did not alter serotonin-induced excitation, and responses to DOM were not reduced by doses of chlorpromazine, that had no local anaesthetic effect on action potentials elicited by DOM and serotonin. These results suggest that DOM is an agonist on at least one type of central serotonin receptor. This receptor may also be a ketanserin (5-HT2) binding site.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1986

Lack of effect of antagonists on serotonin-induced inhibition in rat hippocampus.

Four putative central nervous system 5-hydroxytryptamine antagonists, methysergide, cyproheptadine, metergoline, and ketanserin and also lysergic acid diethylamide were applied by iontophoresis to firing CA1 hippocampal pyramidal cells to test their action on the inhibition produced by 5-hydroxytryptamine. In contrast to a previous report, none of these peripherally active 5-hydroxytryptamine antagonists altered the inhibitory response to submaximal doses of 5-hydroxytryptamine, but they did block after-excitations that followed the inhibitions. All the antagonists and lysergic acid diethylamide produced a depression of firing. When picrotoxin was used to drive the cells, 5-hydroxytryptamine was still able to produce a normal inhibition. The results of this study suggest that CA1 hippocampus is another structure, innervated by serotonergic neurones, where all (peripherally active) serotonin antagonists tested to date are ineffective against 5-hydroxytryptamine induced inhibition.

Action Potentials↗
PubMed1985

Comparison of the effects of amphetamine and a fluorinated analogue on locomotion and exploratory activity in the mouse.

(+)-Amphetamine (AM) and its fluorinated analogue (+)-2-amino-3-fluoro-1-phenylpropane (fluoroamphetamine, FAM) were compared with regard to their effects on locomotor and exploratory activity in mice. Both drugs caused a reduction in spontaneous exploration, but this effect was more marked with FAM than with AM at 1 h after injection. Both compounds increased locomotor activity 10 min after injection, but FAM had sedative effects after 1 h, while AM continued to be stimulatory.

Amphetamine↗
PubMed1984

How toxic are propoxyphene and ethanol in combination?

Ethanol has been claimed to potentiate greatly the lethality of propoxyphene, although published clinical data suggest only an additive effect. Mice were treated intraperitoneally with various doses of propoxyphene hydrochloride and ethanol. Isobolograms of the data show the combination to be less-than-additive for lethality and loss of motor coordination and, at worst, simply additive for sedation.

Animals↗
PubMed1982

Stimulation-evoked changes in extracellular K+ and Ca2+ in pyramidal layers of the rat's hippocampus.

In urethane-anaesthetized rats, ion-selective microelectrodes recorded changes in extracellular K+ and Ca2+ concentrations (delta[K+]omicron and delta[Ca2+]omicron) in pyramidal layers of the hippocampus (mostly in area CA1), which were evoked by fimbrial-commissural stimulation. [K+]omicron increased linearly with frequency of stimulation up to a critical frequency, in the range of 2-5 Hz, where bursts of population spikes appeared, and then rose rapidly to reach a ceiling of 9-12 mM. During continued stimulation, [K+]omicron remained well above the resting level of about 3.0 mM. At the end of stimulation [K+]omicron returned to the base line with a half time of 4-8 s, and a minor undershoot of congruent to 0.5 mM was detectable for 1-2 min. When stimulating at frequencies above the critical value, a sharp fall in [Ca2+]omicron (by an average of one-third below the mean resting level of 1.4 mM) consistently started 1-5 s after the onset of the rapid phase of delta[K+]omicron. [Ca2+]omicron typically reached a minimum in 5-10 s and immediately started to return towards the base line. The recovery of [Ca2+]omicron was often accelerated by an overshoot of up to 0.3 mM; this was followed by a delayed phase of low [Ca2+]omicron for another 2-3 min. During prolonged stimulation at frequencies near 7 Hz, both [Ca2+]omicron and [K+]omicron fluctuated periodically, in time with the appearance and disappearance of bursts of population spikes. Comparable observations were made in area CA2-3 (just external to CA1); in the deeper areas of CA3, in CA4, and in the dentate gyrus, major changes in [K+]omicron and [Ca2+]omicron (as well as bursts of population spikes) were evoked only by prolonged fimbrial stimulation at higher frequencies (congruent to 10 Hz). Thus, although adequate repetitive stimulation of fimbrial-commissural inputs evokes sharp but opposite changes in [K+]omicron and [Ca2+]omicron, the fall in [Ca2+]omicron is consistently much briefer than the rise in [K+]omicron, presumably because of the evanescent character of postsynaptic Ca2+ spikes.

Animals↗
PubMed1982

Depth distribution and mechanism of changes in extracellular K+ and Ca2+ concentrations in the hippocampus.

In the CA1 area of the hippocampus of urethane-anaesthetized rats, the greatest delta[K+]omicron and delta[Ca2+]omicron evoked by repetitive fimbrial-commissural stimulation were always found in the pyramidal cell layer; but there were large increases in [K+]omicron over a wide range of depth, whereas a major fall in [Ca2+]omicron was localized almost exclusively to the level of the pyramidal layer. A sustained focal negative potential was also evoked by fimbrial stimulation; it resembled delta[K+]omicron in time course and depth distribution and therefore probably reflected cellular depolarization caused by increased [K+]omicron. The close correlation between delta[Ca2+]omicron and delta[K+]omicron and the appearance of population spikes (especially in bursts of three to four spikes) indicate that pyramidal cell firing and corresponding K-outward and Ca-inward currents are mainly responsible for the accumulation of K+omicron and the depletion of Ca2+omicron. In CA3 pyramidal areas, delta [K+]omicron and delta[Ca2+]omicron were comparable in magnitude and distribution to changes seen in CA1, but they occurred after a longer latency, and the major delta[Ca2+]omicron had a longer duration, consistent with a more prolonged Ca2+ current.

Animals↗
PubMed1981

Cyclobenzaprine: a possible mechanism of action for its muscle relaxant effect.

Intravenously administered cyclobenzaprine (CBZ) (Flexeril), a clinically used, centrally acting muscle relaxant, abolished muscle rigidity in the intercollicular decerebrate rat. In animals in which the locus coeruleus was lesioned bilaterally previously, CBZ failed to attenuate the electromyogram. In the ventral horn of the cord, which receives a dense noradrenergic innervation from the locus coeruleus, CBZ caused an increase in the metabolism of noradrenaline. In the zona intermedia of the thoracic cord, which is not innervated by the locus coeruleus, CBZ caused only minimal effects on noradrenaline metabolism. Cells in the locus coeruleus were activated by CBZ. The results indicate that in the intercollicular decerebrate rat, an intact, coerulospinal, noradrenergic projection is essential for the muscle relaxant effect of CBZ. Muscle relaxation apparently results from an activation of locus coeruleus neurones, leading to an increased release of noradrenaline in the ventral horn of the cord and the subsequent inhibitory action of noradrenaline on alpha motoneurones.

Amitriptyline↗
PubMed1980

Changes in extracellular Ca2+ and K+ activity accompanying hippocampal discharges.

In rats under urethane anaesthesia, changes in the extracellular activities of K+ and Ca2+ (alpha K and alpha Ca) evoked by fimbrial or entorhinal stimulation and recorded in area CA3 with ion-selective microelectrodes are maximal in the pyramidal cell layers. With 10/s stimulation, alpha K increases by 6--9 mM whereas alpha Ca falls by 0.5--1.0 mM. In contrast with the increase in alpha K, which is distributed over a wide range of depth, the reduction in alpha Ca is particularly sharply limited to the level of pyramidal cell bodies. It is regularly associated with a negative aferpotential in the extracellular field, which presumably reflects a large postsynaptic Ca2+ inward current, apparently predominant in the cell bodies. Repetitive stimulation sometimes evokes spreading depressionlike swings in potential, which are seen only near the pyramidal stratum and are accompanied by massive increases in alpha K (to 30--40 mM) and falls in alpha Ca (to < 0.1 mM). A large Ca2+ influx into pyramidal cells may be of significance for "plastic" aspects of hippocampal function and when excessive, as during repetitive convulsive activity, may be responsible for the necrosis of CA3 neurons.

Animals↗
PubMed1979

Release of exogenous gamma-[3H]aminobutyric acid during seizure activity in chronically denervated and normal cat cortex.

The hypothesis that the seizure susceptibility of chronically denervated cortex is due to interruption of recurrent inhibitory pathways was tested by examining the release of 3H-labeled gamma-aminobutyric acid ([3H]GABA) from chronic slabs and normal cortex of cats. Seizure activity was maintained throughout the test periods in both normal and chronically isolated cortex. When methacholine was used to evoke seizure activity, [3H]GABA release was depressed in both normal and epileptic cortex, suggesting that the mechanism of seizure genesis by cholinomimetics involves suppression of inhibitory neuron activity. Pentylenetetrazol-induced seizures evoked a small, equal increase in [3H]GABA efflux from epileptic and normal cortex. Continuous electrical stimulation evoked a large, and again equal increase in [3H]GABA release. Preseizure efflux of [3H]GABA was the same from chronic slabs and normal cortex in all experiments. Since the interruption of recurrent inhibitory pathways by chronic denervation would result in a decreased resting and seizure-evoked release of [3H]GABA, results obtained do not support the above-mentioned hypothesis.

Animals↗
PubMed1979

Cerebrovascular responses to subarachnoid blood and serotonin in the monkey.

Preliminary in vitro experiments were performed to determine the serum concentration of serotonin in the monkey, and the ability of cyproheptadine to block serotonin and serum-induced contractions in monkey cerebral arteries. Thirty-four cynomolgus monkeys were subsequently used to study changes in regional cerebral blood flow (CBF) obtained by the intracartoid 133Xe technique, and in the angiographic cerebral arterial caliber resulting from subarachnoid injection of artificial cerebrospinal fluid (CSF), blood, and serotonin. Five animals in each injection group were given 1.0 mg/kg intravenous cyproheptadine (a serotonin-blocking agent) during the post-injection period. Subarachnoid injection of artificial CSF produced no change in CBF or arterial caliber. Post-injection administration of cyproheptadine also had no effect on these parameters. A subarachnoid injection of fresh autogenous blood produced a significant but transient (less than 1 hour) decrease in CBF and moderate vasospasm, which lasted at least 3 hours. This vasospasm was essentially unaffected by intravenous cyproheptadine. The CBF and arterial caliber were unchanged following a subarachnoid injection of serotonin at concentrations (5 x 10(-6)M) present in normal monkey serum. In contrast, 5 x 10(-6) M serotonin invariably produced near maximal contractions in the in vitro cerebral artery preparations. Higher (x10) serotonin concentrations caused a transient CBF response similar to that obtained with blood. However, the cerebral vasospasm induced was of shorter duration than that obtained with blood. These results do not support a major role for serotonin in the production of post-subarachnoid hemorrhage vasospasm. Moreover, our data indicate that in vitro experiments do not reflect the ability of serotonin to constrict cerebral arteries in the intact animal.

Animals↗