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H R Olpe

Publications and source records attributed to H R Olpe.

At least 55 records · Page 3Linked to original sources
PubMed1987

Substance P depresses neuronal activity in the rat olfactory bulb in vitro and in vivo: possible mediation via gamma-aminobutyric acid release.

The rat olfactory bulb is an area displaying a particularly high density of substance P receptors in the glomerular cell layer whose functions are unknown. In pilot in vivo experiments we discovered that iontophoretically administered substance P potently depressed the spontaneous firing rate of most unidentified neurons of the rat olfactory bulb. To further elucidate the mechanism of this unexpected depressant effect, we studied the peptide's action in vitro on coronal sections of this brain region. Bath applied and microiontophoretically administered substance P depressed the spontaneous discharge of unidentified glomerular neurons in a dose-dependent fashion. This inhibiting effect is mediated indirectly via the release of another transmitter because it was abolished completely if the standard perfusion medium was replaced by a medium containing zero calcium and high magnesium. It appears that substance P acts by means of releasing GABA which in turn evokes the observed cell depression because the depressant effects were completely abolished by bath-applied bicuculline (10 microM) and picrotoxin (100 microM). In conclusion we propose that substance P indirectly depresses neuronal activity in the glomerular cell layer of the rat olfactory bulb by releasing gamma-aminobutyric acid.

Action Potentials↗
PubMed1987

Alterations in responsiveness of noradrenergic neurons of the locus coeruleus in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.

Locus coeruleus may have a function in central blood pressure regulation and possibly in the pathogenesis of hypertension. In keeping with this notion, we have recently shown that deoxycorticosterone acetate (DOCA)-salt hypertensive rats demonstrate a greater increase in blood pressure induced by locus coeruleus stimulation than control animals. In an attempt to elucidate the underlying mechanisms leading to this alteration in responsiveness of the locus coeruleus, the sensitivity of noradrenergic neurons of the locus coeruleus to the transmitter candidates, epinephrine and glutamate, was investigated in DOCA-prehypertensive (3 days post-DOCA), DOCA chronic hypertensive (6-8 weeks post-DOCA) and control rats using conventional microiontophoretic and single cell recording techniques. Iontophoretically applied epinephrine produced a current-dependent decrease in spontaneous firing rate of all noradrenergic neurons in both DOCA-treated and control rats. Locus coeruleus neurons of DOCA-treated rats at 3 days and 6-8 weeks were less sensitive to epinephrine than those of control rats and the magnitude of the depression in spontaneous firing rate was less. By contrast, iontophoretic applications of glutamate produced an increase in activity of all noradrenergic locus coeruleus neurons. However, there was minimal difference in glutamate sensitivity between neurons of DOCA and control rats. Since the changes in epinephrine sensitivity are apparent not only in the chronic stage but also in the prehypertensive stage, our findings suggest a potential role of the adrenergic input to the locus coeruleus in the pathogenesis of DOCA-hypertension.

Animals↗
PubMed1987

Comparative investigations on the actions of ACTH1-24, somatostatin, neurotensin, substance P and vasopressin on locus coeruleus neuronal activity in vitro.

A considerable number of neuropeptides have been localized immunohistochemically in the area of the locus coeruleus of the rat. The objective of this study was to assess the actions of some of these transmitter candidates on spontaneously active locus coeruleus neurons in vitro. The effects of bath-applied peptides on the discharge rate of individual locus coeruleus neurons were investigated. A midpontine slice preparation of the gerbil brain was used. Excitatory dose-dependent effects were found with four peptides with the following rank order of potency: Substance P, (Arg8)-vasopressin, neurotensin, ACTH1-24. Somatostatin hyperpolarized all neurons tested. Given the pronounced effects seen with substance P, somatostatin and vasopressin in the nanomolar range, it is conceivable that these peptides may have a role in regulating neuronal activity in locus coeruleus.

Animals↗
PubMed1987

Responsiveness of locus ceruleus neurons in hypertensive rats to vasopressin.

We studied the actions of vasopressin administered microiontophoretically onto neurons of the locus ceruleus in rats with deoxycorticosterone-acetate (DOCA)-salt hypertension and in control (normotensive) rats. Rats were studied at 3 days (prehypertensive stage) and 4 to 6 weeks after DOCA-salt treatment (chronic hypertensive stage). Experiments were performed in anesthetized rats using conventional microiontophoretic and single-cell recording techniques. Three days after DOCA-salt administration, the treated rats showed no rise in arterial pressure in comparison with control rats, but 4 to 6 weeks later, the treated rats had significantly greater pressures (p less than 0.01) than controls. Vasopressin administered with currents of 10 to 90 nA for 1 minute produced a current-dependent increase in the firing rate of noradrenergic neurons in all rats. Increases in the firing rate of noradrenergic neurons in DOCA-salt-treated rats, whether in the prehypertensive or the chronic stage, were significantly greater than increases in control rats. These findings indicate that 1) vasopressin can affect neuronal activity in the locus ceruleus and 2) noradrenergic neurons in the locus ceruleus of DOCA-salt-treated rats have an increased responsiveness to the excitatory effects of vasopressin in both prehypertensive and chronic stages of hypertension.

Animals↗
PubMed1986

Glutamate-induced activation of rat locus coeruleus increases CA1 pyramidal cell excitability.

In anesthetized rats, injections of a 0.5 mM glutamate solution into the locus coeruleus (LC) reversibly increased the amplitude of the population spike evoked in CA1 by stimulation of the Schaffer-commissural fiber tract. This effect was absent in N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4)-treated, noradrenaline (NA)-depleted animals. The excitatory postsynaptic potential recorded in the stratum radiatum was unaffected following the glutamate injections. Systemic administration of the NA-uptake inhibitor desipramine also produced an increase in population spike amplitude. The findings demonstrate that activation of LC neurons increases pyramidal cell excitability in vivo.

Animals↗
PubMed1986

Pharmacological characterization of the receptor mediating the adrenergic inhibition of responses to substance P in the cingulate cortex.

The excitatory responses of neurones in the anterior cingulate cortex of the rat to iontophoretically applied substance P (SP) are reduced by noradrenaline (NA) applied iontophoretically or released from noradrenergic pathways. In order to determine the receptor involved in this inhibitory effect we have studied the effects of a number of receptor-specific adrenergic agonists and antagonists on responses of cingulate neurones to SP in rats anaesthetized with chloral hydrate. Low iontophoretic currents (0-15 nA) of NA, adrenaline and the beta-agonist, clenbuterol, all strongly reduced responses to SP. Isoprenaline was also effective but less consistently so, although problems were experienced with its iontophoretic release from micropipettes. The alpha 1-agonists, phenylephrine and methoxamine were also able to reduce responses to SP. However, this reduction required higher iontophoretic currents (15-60 nA) and was associated with depressant effects on baseline firing rate. The alpha 2-agonist clonidine was only weakly active at high currents and this too was associated with depression of baseline firing. Similar weak effects were noted with dopamine. The inhibitory effects of NA on SP responses were convincingly blocked or reversed by the beta-antagonist, practolol, but not by the alpha 1-antagonist, prazosin. The reduction of SP responses by phenylephrine was also blocked by practolol but unaffected by prazosin. Finally, reduction of SP excitations by activation of the coeruleocortical pathway was also blocked by practolol applied iontophoretically to the cortical cells. These results are consistent with the hypothesis that the effect of NA on SP responsiveness in the cingulate cortex is mediated by beta-adrenoreceptors.

Albuterol↗
PubMed1986

Testing of prototype antiepileptics in hippocampal slices.

The effects of six prototype anticonvulsant drugs, phenytoin, carbamazepine, midazolam, phenobarbital, ethosuximide and sodium valproate, were evaluated in two different experimental models of epileptiform activity using the in vitro slice preparation from the rat hippocampus. The relative potencies of the agents were determined: a) in the complete absence of synaptic transmission by recording spontaneous burst firing from the CA 1 pyramidal cell layer in a low calcium high magnesium solution and b) during blocked synaptic inhibition by observing the activity of each drug upon orthodromically evoked population spikes in penicillin containing medium. The rank order of potencies was a) in low Ca2+: carbamazepine, phenytoin, midazolam, phenobarbital, valproate, ethosuximide; b) in penicillin containing medium: midazolam, phenobarbital, carbamazepine, phenytoin, valproate, ethosuximide. These observations illustrate that the use of multiple paradigms is warranted when examining the mechanisms of action of new anticonvulsants.

Animals↗
PubMed1986

Dose pipecolic acid interact with the central GABA-ergic system?

Several previous studies have suggested a strong GABA-mimetic action of the endogenous brain imino acid, L-pipecolic acid (L-PA). In the present study, these observations were evaluated using electrophysiological and neurochemical methods. In contrast to published data our electrophysiological studies on rat cortical neurones in situ showed only a weak, but bicuculline-sensitive depressant action of L-PA on cortical neurones. Furthermore, L-PA proved to have no affinity for any of the three components of the GABA-benzodiazepine-chloride channel receptor complex. However, using a modification of published methods a weak affinity for the GABA-B receptor site was demonstrated (IC50 = 1.8 X 10(-3) M). L-PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. In conclusion, these results are not compatible with a strong in vivo interaction between L-PA and GABA-mediated inhibitory transmission.

Animals↗
PubMed1986

Comparative electrophysiological investigations on oxiracetam and piracetam.

Acute effects of the two psychogeriatric agents, oxiracetam (ISF 2522) and piracetam, were studied in rat brain tissue in vivo and in vitro. In vivo, both compounds elicited a moderate activation of locus coeruleus neuronal discharge rate with doses of 1,000 mg/kg ip. Neither of the compounds however affected spontaneous firing rates of neurons of the medial septal nucleus in vivo if administered intravenously. In the hippocampal slice preparation, the two compounds elicited weak but opposite effects on extracellularly recorded field potentials if administered in high concentrations. Whereas oxiracetam elicited a moderate depressant effect on pyramidal cell excitability, piracetam increased it in a reversible fashion. Piracetam had no effect on the excitatory postsynaptic potential (epsp) evoked by stimulation of the Schaffer commissural fiber pathway but oxiracetam reversibly attenuated it at concentrations of 100 microM to 1 mM. In intracellular recordings from CA1 pyramidal neurons in vitro, piracetam had no effect on resting membrane potential, conductance or afterhyperpolarizations. Oxiracetam, however, slightly hyperpolarized six out of twelve CA1 neurons. Membrane conductance was not affected. In conclusion, electrophysiological studies with the psychogeriatrics oxiracetam and piracetam revealed that the drugs exert weak effects on rat brain tissue in acute experiments, and demonstrated that the two compounds differ in their pharmacological profile.

Animals↗
PubMed1985

Reduced activity of locus coeruleus neurons in hypertensive rats.

The influence of blood pressure on locus coeruleus (LC) neuronal activity was investigated in chloral hydrate anesthetized rats. Mean spontaneous firing rate of LC neurons was reduced by 25% in deoxycorticosterone acetate (DOCA-salt) treated Sprague-Dawley rats and by 19% in spontaneously hypertensive rats (SHR) as compared to their corresponding control animals. In acute experiments performed on normotensive rats, peripherally induced blood pressure changes elicited reciprocal changes in cell firing of the majority of LC neurons. The findings suggest that LC may have a role in long-term regulation of blood pressure.

Adrenergic Fibers↗
PubMed1985

Tachykinin responses in the rat cingulate cortex: a comparison of the effects of iontophoretically applied substance P and neurokinin A.

The effects of substance P and neurokinin A were compared on spontaneously active cells in the anterior cingulate cortex of the rat. Most neurones were strongly excited by the iontophoretic applications of both peptides. However, many of the superficially located cells were clearly depressed by substance P but unaffected by the application of neurokinin A or even weakly excited. The results indicate that neuronal responses to tachykinins in this brain area may be mediated, at least in part, by separate receptors.

Animals↗
PubMed1985

Trimipramine, a tricyclic antidepressant exerting atypical actions on the central noradrenergic system.

Trimipramine is a tricyclic antidepressant which has only weak effects on noradrenergic systems. Its mechanism of action is not understood, but its clinical effectiveness has been proven over a period of 20 years. In the present investigation, trimipramine was shown to have no effect on noradrenaline (NA)-stimulated adenylate cyclase activity after either acute or once daily application for 28 days. There was no change in the KD or Bmax of [3H]DHA binding, demonstrating a lack of effect on beta-adrenergic receptors. However, it did exert effects on the cortical noradrenergic projection of the locus coeruleus and these effects were opposite to those described for typical antidepressants. In acute experiments, systemic injections of trimipramine potently activated locus coeruleus neurons and produced a reduction in the depressant action of noradrenaline administered iontophoretically to neurons in the cingulate cortex. After 4 weeks' treatment with a daily injection of 30 mg/kg i.p. trimipramine, cingulate cortical neurons became supersensitive to the action of iontophoretically applied noradrenaline. Although it is unknown whether these effects are related to the therapeutic efficacy of trimipramine, the results demonstrate that the down-regulation of central noradrenergic sensitivity in the rat is not a prerequisite for clinical efficacy of antidepressants in man.

Action Potentials↗
PubMed1985

Electrophysiological and neurochemical investigations on the action of carbamazepine on the rat hippocampus.

Carbamazepine moderately depressed the input fiber volley resulting in attenuation of the dendritic epsp and the population spike in CA1 of rat hippocampal slices with a threshold concentration of 20 microM. The depressant effect on the population spike was not antagonized by the adenosine receptor blocker caffeine. Paired-pulse inhibition was not affected by carbamazepine (40 microM). Epileptic-like rhythmic discharge of CA1 neurons in medium containing low Ca2+/high Mg2+ was attenuated at even lower concentrations of carbamazepine (8 microM) indicating that there was also a postsynaptic site of action. Imipramine being significantly more potent than carbamazepine in the rabbit corneal test for local anaesthetic activity had no effect on the population spike (20 microM). In neurochemical studies, carbamazepine reduced the [22Na]- and [3H]L-glutamate efflux induced by potassium and veratridine from hippocampal slices with a threshold concentration of 10 microM. The drug (400 microM) failed to affect Na+-dependent binding of [3H]L-glutamate to hippocampal synaptic membranes. In conclusion, the present findings demonstrate pre- and postsynaptic depressant actions of carbamazepine in CAI of hippocampus.

Anesthetics, Local↗
PubMed1985

Stereoselectivity of L-baclofen in hippocampal slices of the rat.

Extra- and intracellular recording from hippocampal slices of the rat revealed the following effects when baclofen (BF) (0.1-10 microM) was added to the perfusion fluid: a block of synaptic potentials evoked by stimulation of stratum radiatum; a direct hyperpolarization and a conductance increase (for potassium ions) of CA1 pyramidal cells. All this activity was found in the L- none in the D-enantiomer. D-BF did not antagonize the action of L-BF.

Animals↗
PubMed1985

Neuronal sensitivity to substance P is increased after repeated treatment with tranylcypromine, carbamazepine or oxaprotaline, but decreased after repeated electroconvulsive shock.

The responsiveness of neurones in the cingulate cortex of the rat to the excitatory effects of iontophoretically applied substance P (SP) was determined after chronic administration of several drugs known to possess antidepressant actions. The agents tested were tranylcypromine, carbamazepine and oxaprotiline [(+) and (-)isomers]. Twenty-four to 36 hr after the last of 14 consecutive daily treatments there was an increase in neuronal sensitivity to substance P with all three drugs. The two isomers of oxaprotaline were equally active in inducing this change in sensitivity. None of the agents significantly altered responses to substance P after a single acute treatment. Responsiveness to substance P was also tested one day after the last of 14 daily treatments with electroconvulsive shock. In this case there was a marked reduction of the sensitivity of cingulate neurones to substance P with no apparent change in responsiveness to acetylcholine. A single shock treatment did not detectably alter responses to substance P.

Animals↗
PubMed1985

Reduced activity of locus coeruleus neurons in hypertensive rats.

The effect of blood pressure on the neuronal activity of the locus coeruleus (LC) was investigated by means of electrophysiological techniques in rats anaesthetized with chloral hydrate. The mean neuronal discharge rate of noradrenergic neurons of the LC was reduced by 19% in spontaneously hypertensive rats (SHR) and by 25% in deoxycorticosterone acetate (DOCA)-salt hypertensive rats compared with their corresponding controls. The cellular activity of 27 out of 40 neurons was reversibly suppressed by acute, peripherally induced blood pressure increases in normotensive rats. Five neurons were reversibly activated and eight neurons were not affected. Conversely, acute decreases in blood pressure stimulated the neuronal activity of the LC in 10 out of 16 neurons. These findings support the hypothesis of the LC having a role in both short and long term regulation of blood pressure.

Action Potentials↗
PubMed1985

Comparative electrophysiological investigations with Hydergine and other psychogeriatric agents on corticol and subcortical structures.

The action of systemically administered Hydergine on the spontaneous neuronal firing of neurons located in various brain areas of the anaesthetized rat was investigated using conventional extracellular single cell recording techniques. Whereas locus coeruleus neurons were activated by both acute and repetitive injections of the drug, spontaneously active neurons of the medial septal nucleus, pyramidal cells of the hippocampus and unidentified neurons of the cingulate cortex were not affected. The possible functional consequences of the drug's activating action on locus coeruleus noradrenergic neurons are discussed. In view of the finding that noradrenaline affects the signal-to-noise ratio in various brain areas and given the widespread innervation pattern of noradrenergic fibers arising from locus coeruleus, Hydergine through its action on this brain area may potentially affect many brain regions.

Animals↗