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Biomedical subjects

H R Olpe

Publications and source records attributed to H R Olpe.

At least 73 records · Page 4Linked to original sources
PubMed1984

Monoaminergic modulation of the sensitivity of neurones in the cingulate cortex to iontophoretically applied substance P.

The interactions of noradrenaline (NA) and 5-hydroxytryptamine (5-HT) with substance P (SP) were studied on single neurones in the anterior cingulate cortex of the rat. Iontophoretic application of 5-HT potentiated the excitatory responses of some neurones to SP and reduced responses of others. However these effects were usually accompanied by parallel changes in baseline firing rate i.e. increase and decrease respectively. In studies where carbachol (CCh) was used as a control the excitatory responses to this substance were always altered in a similar fashion to those to SP. The effects of NA on SP-responses were more consistent. This amine caused a reduction of response to SP regardless of whether there was an increase, decrease, or no change in baseline firing rate. Responses to SP could be reduced on many cells in the absence of changes in response to CCh and even on some cells where CCh responses were concurrently enhanced. Lesions of the locus coeruleus which resulted in a depletion of NA in the ipsilateral cingulate cortex gave rise to a substantial increase in sensitivity of neurones to SP two weeks later. However, lesions of the median raphe(MR)-nucleus which strongly reduced cortical 5-HT had no detectable effect on SP-responses. The data indicate that both NA and 5-HT can alter cortical neurone-sensitivity to SP but that the former amine may be involved in a more specific and possibly a functional interaction.

Acetylcholine↗
PubMed1984

Multiple changes in the sensitivity of cingulate cortical neurones to putative neurotransmitters in ageing rats: substance P, acetylcholine and noradrenaline.

The responsiveness of neurones in the anterior cingulate cortex to iontophoretically applied substance P(SP), acetylcholine (ACh), noradrenaline (NA) and GABA was compared in young (3-4 months) and old (24-30 months) rats. Neurones in the old rats were less sensitive to the depressant effects of NA but not GABA. These cells were also less sensitive to the excitatory actions of ACh but markedly more sensitive to those of SP. Such changes in responsiveness could be involved in the deficits in cerebral function which often occur in old age.

Acetylcholine↗
PubMed1984

The sensitivity of hippocampal pyramidal neurons to serotonin in vitro: effect of prolonged treatment with clorgyline or clomipramine.

The sensitivity of hippocampal pyramidal neurons to the depressant action of serotonin was studied in hippocampal slices obtained from rats treated repetitively with clomipramine (10 mg/kg i.p.; 10 days or 4 weeks), with clorgyline 0.3 mg/kg s.c.; 10 days) or with the vehicle. Whereas clorgyline produced a very pronounced subsensitivity to serotonin, a moderate, non-significant reduction in sensitivity was observed with clomipramine. These electrophysiological findings are consistent with previous biochemical studies.

Animals↗
PubMed1984

Activation of the noradrenergic projection from locus coeruleus reduces the excitatory responses of anterior cingulate cortical neurones to substance P.

The effects of activating the coeruleocortical pathway on responses of cingulate cortical cells to substance P was determined in the rat. The pathway was activated by means of small injections of glutamate, via a stereotaxically positioned cannula, directly into the locus coeruleus. Such injections greatly reduced the excitatory responses of cortical cells evoked by the iontophoretic application of substance P. Variation in the dorsal and lateral sites of injection suggested that the locus coeruleus was the important position for eliciting these effects. Depletion of cortical noradrenaline greatly reduced the ability of these injections to inhibit the substance P responses. Injections of glutamate into the locus coeruleus did not reduce cortical cell responses to acetylcholine. Parenteral administration of propranolol but not phenoxybenzamine blocked the effects of the glutamate injections on the substance P responses. These data support our previous suggestion that the central noradrenergic system may have a functional inhibitory effect on responsiveness to substance P in the cingulate cortex.

Animals↗
PubMed1984

An increase in sensitivity of rat cingulate cortical neurones to substance P occurs following withdrawal of chronic administration of antidepressant drugs.

The sensitivity of neurones in the cingulate cortex of the rat to iontophoretically applied substance P (SP) was tested one hour after a single dose of various antidepressant drugs and also 1 day following the termination of a chronic dosing schedule (14 once daily injections) of the same agents. One hour after a single injection of desipramine (DMI), chlorimipramine (CMI), trimipramine (TMI) or zimelidine ( ZIM ) (all at 10 mg kg-1 i.p.) there was no change in the mean size of excitatory responses to SP compared to those before the injection. There was a tendency towards a decrease in the TMI group. One day following the last of 14 consecutive daily injections (10 mg kg-1 i.p.) of the above agents there was a significant increase in the size of excitatory responses to SP compared to those in rats receiving daily saline injections. However, 14 days of treatment with DMI did not alter the responses to L-glutamate. Similar chronic dosing schedules with either diazepam (5 mg kg-1) or fluphenazine (5 mg kg-1) did not affect the responses to SP. Thus chronic but not acute administration of antidepressant drugs results in an increase in the sensitivity of neurones, in the cingulate cortex of the rat, to SP.

Action Potentials↗
PubMed1984

On the role of the baseline firing rate in determining the responsiveness of cingulate cortical neurons to iontophoretically applied substance P and acetylcholine.

The relationship between baseline firing rate and the magnitude of excitatory responses to iontophoretically applied substance P (SP) and acetylcholine (ACh) was determined for neurons in the anterior cingulate cortex of the rat. Whereas the size of responses to ACh was positively correlated with the level of ongoing neuronal activity, no correlation, either positive or negative, could be demonstrated for responses to SP. It seems unlikely that the excitatory effects of SP in this brain area result from release of endogenous ACh.

Acetylcholine↗
PubMed1984

Microinjection of vasopressin into the locus coeruleus of conscious rats.

To determine whether vasopressin plays a role in central neural control of cardiovascular function by acting on the locus coeruleus we monitored arterial pressure and heart rate responses to graded injections of vasopressin (1-30 ng, 0.1-0.3 microliter) in the locus coeruleus of conscious, restrained rats. Cannulas were stereotaxically implanted in the locus coeruleus 2-5 days prior to experiment. Injections of vasopressin into the locus coeruleus produced dose-related increases in mean arterial pressure (12 +/- 2 to 57 +/- 6 mmHg) and heart rate (27 +/- 6 to 123 +/- 16 beats/min), which lasted over 1 h at the highest dose. Injection of the antipressor vasopressin antagonist d(CH2)5Tyr(Me) arginine vasopressin (10 ng) into the locus coeruleus blocked the cardiovascular responses to vasopressin. Administration of vasopressin into an area lateral to the locus coeruleus had no effect on mean arterial pressure but produced an increase in heart rate. Equivalent doses of saline, angiotensin II, and norepinephrine (NE) had minimal or opposite (NE) effects on arterial pressure and heart rate. Peripheral alpha-adrenergic blockade with phentolamine and beta-adrenergic blockade with propranolol blocked the cardiovascular responses to injection of vasopressin in the locus coeruleus. These results suggest that vasopressin may act in the region of the locus coeruleus to exert a central action on the cardiovascular system that is mediated by a stimulation of sympathetic outflow.

Animals↗
PubMed1983

Decreased activity of locus coeruleus neurons in the rat after DSP-4 treatment.

The activity of noradrenergic neurons of the rat locus coeruleus was investigated at 10 and 50 days after the administration of DSP-4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzyl-amine), a selective noradrenergic neurotoxin. The mean neuronal firing rate in control animals was 2.4 Hz. In contrast, DSP-4 animals had lower rates of 1.2 Hz at 10 days and 1.7 Hz at 50 days. Histological examinations revealed no morphological changes of locus coeruleus cell bodies at either the 10- or 50-day time points. These results suggest that DSP-4 can impair neuronal activity of the locus coeruleus without altering the structural appearance of locus coeruleus perikarya.

Action Potentials↗
PubMed1983

The action of anticonvulsant drugs on the firing of locus coeruleus neurons: selective, activating effect of carbamazepine.

The action of various doses of intraperitoneally administered carbamazepine, ethosuximide, Na-valproate, phenobarbital and diphenylhydantoin on the neuronal firing rate of presumed noradrenergic neurons of the locus coeruleus was investigated in the anaesthetized rat. Carbamazepine was the only compound which produced a statistically significant, dose-dependent activation of these neurons. The other anticonvulsant drugs caused a small but non significant reduction in locus coeruleus cell firing. It is concluded that this brain nucleus is not a main target of anticonvulsant drugs.

Animals↗
PubMed1983

The locus coeruleus: actions of psychoactive drugs.

The locus coeruleus is one of the most thoroughly investigated mammalian brain areas. Its fibers innervate large parts of the neuraxis, in particular, areas involved in cognitive functions such as the cortex and the hippocampus. A role of locus coeruleus has been proposed in such processes as memory, the control of vigilance, blood pressure and others. Results obtained in this and other laboratories demonstrate that the firing rate of locus coeruleus neurons is affected by a great number of psychoactive agents such as antidepressants, minor tranquillizers, neuroleptics, psychostimulants and certain psychogeriatric drugs. We have attempted to correlate the data obtained on the cell bodies of locus coeruleus with studies reporting effects on terminal areas and thereby gain an overall view of the action of the above mentioned drugs on this cell system. The activity of noradrenergic neurons in locus coeruleus is thought to correlate with the level of cortical vigilance. Special emphasis is placed on the finding that a number of drugs which exert a positive effect on cognitive functions in man and animals increase the firing rate of the rat locus coeruleus neurons.

Action Potentials↗
PubMed1983

Altered sensitivity of forebrain neurones to iontophoretically applied noradrenaline in aging rats.

Responses of unidentified neurones in the rostral cerebral cortex to iontophoretically applied noradrenaline and GABA were compared in young (3-4 months old) and old (22-24 months old) albino rats. Depressant responses to noradrenaline were smaller in the older animals and this was manifested particularly as a decrease in response duration. Depressant responses to GABA did not differ significantly in the two groups. The results indicate that neurones in the cerebral cortex, as in the cerebellum, exhibit a decrease in postsynaptic responsiveness to noradrenaline with advancing age.

Aging↗
PubMed1982

A structure-activity profile of substance P and some of its fragments on supraspinal neurones in the rat.

Responses of neurones in the cingulate cortex to iontophoretically applied substance P (SP) were compared to its various C-terminal fragments. Fragments as short as the hexapeptide sequence were at least as active in increasing neuronal firing as the parent molecule. The pentapeptide sequence was much less active and the tripeptide sequence inactive. Compared on a current basis the octa-, hepta- and hexapeptides all evoked larger responses than the full sequence SP. In addition, the nonapeptide N-terminal sequence of SP had no effect on any neurone on which it was tested.

Animals↗
PubMed1982

Excitatory effects of ACTH on noradrenergic neurons of the locus coeruleus in the rat.

Responses of presumed noradrenaline-containing neurons in locus coeruleus (LC) to iontophoretically applied ACTH were determined. The full sequence ACTH1-39 and the partial sequence ACTH1-24 were excitatory on the majority of neurons tested. The partial sequence ACTH27-39 was without effect on most neurons. The presence of ACTH-containing fibers in LC together with the present results may suggest a controlling influence of the peptide on the noradrenaline system.

Adrenocorticotropic Hormone↗
PubMed1982

Vincamine: a psychogeriatric agent blocking synaptic potentiation in hippocampus.

The action of vincamine on the physiology of the CA1 region of the in vitro hippocampal slice preparation was investigated. At concentrations of 1, 10 and 100 microM, a five-minute perfusion with vincamine did not affect the synaptically-mediated activation of pyramidal neurons evoked by stimulation of the Schaffer-commissural fiber system. The effect of vincamine on the excitability of the pyramidal neurons was investigated by studying its effect on the antidromically-elicited field potential and the input-output relation of Schaffer-commissural fiber input. No effect on either of the two parameters was seen at a concentration of 100 microM of vincamine. Vincamine did, however, attenuate both the post-tetanic (PTP) and long-term potentiation (LTP) evoked by repetitive stimulation of the Schaffer-commissural fiber system. At a concentration of 100 microM of vincamine, PTP was significantly reduced and LTP was almost completely suppressed.

Action Potentials↗
PubMed1982

The action of piracetam on the electrical activity of the hippocampal slice preparation: a field potential analysis.

The action of various doses of piracetam on the electrical responses of in vitro hippocampal slices from the rat was investigated. Piracetam increased dose dependently the amplitude of the population spike response of pyramidal neurons evoked by stimulation of the stratum radiatum. Piracetam began to affect the population spike at a dose of 100 microM and consistently increased it at a dose of 1 mM. The drug had a rapid onset of action and recovery was seen within a few minutes following its removal. The response of the pyramidal neurons to antidromic stimulation was not affected by piracetam at concentrations up to 50 mM. Also, neither the amplitude nor the slope of the dendritic response was changed by the drug.l Piracetam also did not affect either posttetanic or long-term potentiation of synaptic potentials. These findings suggest that the drug does not act through depolarization of the pyramidal cells or potentiation of the synaptic processes located on their dendrites. The action of piracetam on the feedforward- and feedback-mediated inhibition of pyramidal cells by basket cells was investigated in several series of experiments. At concentrations of 1 and 10 mM, piracetam did not change either of the two types of inhibitory mechanisms. Several hypothetical sites of action of piracetam are discussed.

Animals↗
PubMed1982

The effect of vincamine, hydergine and piracetam on the firing rate of locus coeruleus neurons.

Vincamine, hydergine and piracetam are used for the treatment of memory disturbances as well as for the treatment of various other brain dysfunctions seen in the elderly patient. The action of these three psychogeriatric compounds on the activity of noradrenergic neurons in the rat locus coeruleus was investigated. All three compounds, when administered intraperitoneally, increased the firing rate of noradrenergic neurons in the chloral hydrate anaesthetized animals. Vincamine and hydergine had a similar potency producing a maximal mean increase of about 70% at a dose of 1 mg/kg. Likewise, piracetam was significantly less potent eliciting a 30 to 40% increase in firing at doses of 300 and 1000 mg/kg, respectively. A role for the locus coeruleus in processes related to attention, cortical and behavioral arousal, learning and memory has been proposed on the basis of behavioral and electrophysiological experiments. In the awake rat, the firing rate of noradrenergic neurons in this brain nucleus has previously been shown to relate directly to the level of vigilance. The activating action of vincamine, hydergine and piracetam on these neurons may be linked with some of the drugs' beneficial therapeutic effects.

Animals↗