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Biomedical subjects

J Vetulani

Publications and source records attributed to J Vetulani.

At least 55 records · Page 3Linked to original sources
PubMed1991

Role of calcium channels in effects of antidepressant drugs on responsiveness to pain.

The effect of acute and chronic treatment with three antidepressant drugs on the cortical L-type calcium channel (measured as [3H]nitrendipine binding sites) and on the responsiveness to pain (assessed in the hot-plate test) was tested on the Wistar rat. Acute administration of antidepressants did not affect the characteristics of calcium channels and did not significantly prolong the hot-plate latency. However, a combination of antidepressants with nifedipine brought about analgesia. Chronic administration of imipramine did not significantly affect the characteristics of calcium channels but produced a moderate analgesic effect. In contrast, chronic administration of citalopram and chlorprothixene increased the density of [3H]nitrendipine binding sites and induced hyperalgesia, which was nullified by acute administration of nifedipine. The results confirm that calcium channels may be involved in analgesia and hyperalgesia and indicate that chronic treatment with some antidepressant may induce an increase in the density of cortical calcium channels.

Animals↗
PubMed1991

Opposite action of oxytocin and its peptide antagonists on social memory in rats.

The synthetic 1-beta,beta-disubstituted analogues of [1-deamino]-oxytocin, [1'-(1'-thio-4'-methylcyclohexane)-acetic acid 1]-oxytocin (MeCAOT) a peripheral oxytocin antagonist, and [1'-(1'-methyl-4'-thiopiperidine)-acetic acid 1]-oxytocin (MePAOT), devoid of peripheral anti-oxytocin activity, were found to improve social memory of rats. The social memory in rats was disrupted by a wide range of doses of oxytocin (6-750 mU/kg) and this amnestic effect of oxytocin was antagonised by MePAOT and MeCAOT.

Animals↗
PubMed1991

Involvement of protein kinase C in the mechanism of in vitro effects of imipramine on generation of second messengers by noradrenaline in cerebral cortical slices of the rat.

Imipramine did not significantly inhibit the noradrenaline or isoproterenol-induced cyclic AMP accumulation in rat cerebral cortical slices, but inhibited the potentiation of this response by protein kinase C activator, a phorbol ester 12-O-tetradecanoyl-phorbol 13-acetate. In low concentrations (0.1-1 microM) it prevented the inhibitory effect of the phorbol ester on accumulation of inositol phosphate induced by noradrenaline, while in higher concentrations it inhibited the response by itself. Imipramine did not bind to beta-adrenoceptors but was an effective blocking agent of alpha 1-adrenoceptors (Ki = 38.1 nM). The data suggest that imipramine acts within the noradrenergic cyclic AMP generating system on two targets: inhibiting protein kinase C and blocking the alpha 1-adrenoceptor; both actions may reduce the alpha-adrenoceptor potentiation of beta-adrenoceptor-mediated cyclic AMP generation.

Adenylyl Cyclases↗
PubMed1991

Different mechanisms of beta-adrenoceptor down-regulation by chronic imipramine and electroconvulsive treatment: possible role for protein kinase C.

The aim of this study was to find out how protein kinase C (PKC) is involved in down-regulation of the beta-adrenoceptor in cortical slices of rats subjected to antidepressant treatments. The responses of the cyclic AMP generating system to forskolin, isoproterenol, and noradrenaline were tested in the absence and presence of a PKC activator, 12-O-tetradecanoylphorbol 13-acetate (TPA). The antidepressive treatments applied were chronic administration of imipramine and electroconvulsive shock. The potentiating effect of the phorbol ester on cyclic AMP response to isoproterenol was retained in imipramine-treated animals and even accentuated in rats subjected to electroconvulsive treatment; the TPA effect on noradrenaline-induced cyclic AMP response was blunted in rats receiving imipramine, but augmented in those receiving electroconvulsive treatment. In imipramine-treated rats the beta-down-regulation was still evident in the presence of TPA; after electroconvulsive treatment the phorbol ester-induced potentiation was so high that no significant beta-down-regulation could be observed. No procedure affected the response to forskolin. The beta-down-regulation that develops during chronic imipramine treatment differs from that caused by chronic electroconvulsive treatment; in both cases it is not related to the direct effect on adenylate cyclase.

Adenylyl Cyclases↗
PubMed1991

Avoidance learning during antidepressant withdrawal in mice.

Shuttle-box avoidance acquisition, locomotor activity and density of adrenoreceptors in the cerebral cortex have been evaluated, in CD-1 mice, during withdrawal from repeated treatment with desipramine or mianserin (5 or 14 daily injections of antidepressant drug, 10 mg kg-1). Withdrawal from mianserin did not produce any behavioural or neurochemical change. Mice withdrawn from desipramine exhibited avoidance facilitation, when training started 24 h (but not 72 or 120 h) after the last injection. Locomotor activity was not affected and no change was found in the density of beta-adrenoreceptors. An up-regulation of alpha 2- and, to a lesser extent, of alpha 1-adrenoreceptors, occurred 72 h following desipramine withdrawal. However, the assessment of the role played by these neurochemical changes in the avoidance facilitation observed during withdrawal from the antidepressant treatment requires further study.

Animals↗
PubMed1990

Cortical dihydropyridine binding sites and a behavioral syndrome in morphine-abstinent rats.

The density of cortical [3H]nitrendipine binding sites was elevated by over 40% in rats rendered morphine-abstinent by administration of naloxone after chronic treatment with morphine. The morphine-abstinent rats had significantly shortened response latencies in the hot-plate test. Nifedipine treatment abolished the signs of abstinence and normalized the hot-plate latencies in morphine-dependent, naloxone-treated rats. The results indicate that the symptoms of abstinence are related to a functional state of cortical dihydropyridine-sensitive calcium channels.

Animals↗
PubMed1990

Effect of repetitive electroconvulsive treatment on sensitivity to pain and on [3H]nitrendipine binding sites in cortical and hippocampal membranes.

The effect of electroconvulsive shock (ECS) on the responsiveness to pain (measured by the hot-plate test) and on the characteristics of L-type calcium channels (measured as [3H]nitrendipine binding sites) in the cortex and hippocampus was tested on the Wistar rat. In animals receiving a single ECS, the calcium channel density and affinity 24 h after treatment did not differ from the controls; the response to pain was also at the control level. Repeated ECS (eight once-daily shocks) resulted in an increased responsiveness to pain (shortening of response latency) and in an increase in the density of cortical, but not hippocampal, calcium channels. The KD value for [3H]nitrendipine binding sites in either brain region remained unaltered by ECS. The calcium channel antagonist nifedipine, which by itself did not significantly alter the response to pain, prevented the enhancement of pain sensitivity brought about by ECS. The results suggest activation of calcium-dependent mechanisms by repeated ECS and confirm the involvement of calcium channels in pain mechanisms.

Animals↗
PubMed1990

Pretreatment with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline accelerates the electroshock-induced decrease in density of beta-adrenoceptors but not functional downregulation.

Intrapritoneal injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats significantly reduced the density of alpha 1- and alpha 2-adrenoceptors in the cerebral cortex, without affecting beta-adrenoceptors. A single dose of EEDQ markedly accelerated the development of downregulation of beta-adrenoceptors induced by a short series of electroshocks. The accumulation of cAMP, induced by isoproterenol, was unchanged in rats treated with EEDQ, while the effect of noradrenaline was reduced, to the level observed after isoproterenol alone, indicating the attenuation of alpha-adrenoceptor function. The isoproterenol-induced accumulation of cAMP was not changed by EEDQ nor electroshock, not by the combined treatment. The stimulatory action of noradrenaline was reduced after EEDQ alone or in combination with electroshock, but the effect of electroshock alone was insignificant. The results suggest that the acceleration of downregulation of beta-adrenoceptors after combined treatment with an alpha-adrenoceptor blocking agent is related to elimination of the alpha-adrenergic potentiation of accumulation of cAMP mediated by beta-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1990

Second messengers: rate of formation as an index of receptor reactivity.

Generation of a second messenger upon stimulation of a metabotropic membrane receptor is the first biochemical reaction in the process of translation of a signal approaching the cell into the cellular response. Thus, the measurement of the rate of generation of these intracellular chemical signals may be a convenient way to assess the functional state of the receptor. The basic methodologies for assessment of the formation of cyclic AMP and inositol phosphates are described. Examples from our laboratory show how the measurement of these messengers may be employed in studies on receptor adaptation to permanently changed neurotransmitter availability, the discrepancy between the changes of receptor densities and functional up- or down-regulation, cooperativity of receptors, mechanisms of the action of drugs, neurotransmission changes in senescence and comparative neurochemistry.

Animals↗
PubMed1989

Increased responsiveness of the cerebral cortical phosphatidylinositol system to noradrenaline and carbachol in senescent rats.

The responsiveness of cerebral cortical alpha 1-adrenoceptors and cholinergic muscarinic M1 receptors was assessed in young (3 months) and aged (24 months) male Sprague-Dawley rats. The measure of responsiveness was the accumulation of inositol phosphate (IP) formed in [3H]myo-inositol-preloaded cerebral cortical slices in the presence of lithium, following stimulation with various concentrations of noradrenaline (1-300 microM) and carbachol (5-1000 microM). In old rats the maximum response to noradrenaline was higher by 80%, and that to carbachol by 33%, indicating an increased responsiveness of the investigated receptors in senescence.

Aging↗
PubMed1989

An in vivo procedure for the selective inactivation of rat brain cerebral cortical alpha-adrenoceptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).

Intraperitoneal administration of 0.8 mg/kg N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to rats significantly reduced alpha-adrenoceptor binding in cerebral cortical membranes without affecting beta-adrenoceptor sites. A selective reduction in alpha 1-adrenoceptors was achieved by injecting yohimbine prior to EEDQ, whereas prazosin pretreatment yielded a selective reduction in alpha 2-adrenoceptor binding. Administration of EEDQ decreased norepinephrine-stimulated inositol phosphate and cyclic adenosine monophosphate (cAMP) accumulation in cerebral cortical tissue as well as the cAMP response to isoproterenol in combination with 6-fluoronorepinephrine without modifying the second messenger response to isoproterenol alone. The results suggest that, under the proper conditions, EEDQ administration can selectively diminish rat brain alpha-adrenoceptor number and function, yielding a procedure that may be useful for defining the behavioral and physiological properties of these sites.

Adrenergic alpha-Antagonists↗
PubMed1989

Pentobarbital-induced hyperactivity in mice: negligible role of opioid mechanisms.

Subhypnotic doses (10 and 20 mg/kg) of pentobarbital significantly elevated locomotor activity measured for 30 min in CD-1 mice. The hyperactivity was also observed in mice recovering from pentobarbital-induced (50 mg/kg) sleep (measurements starting 15 min after recovery of righting reflex). Naloxone in doses up to 4 mg/kg did not affect significantly the pentobarbital-induced hyperactivity in any experiment; a dose of 8 mg/kg only partially attenuated the hyperactivity induced by a dose of 20 mg/kg of pentobarbital, but did not affect significantly either the stimulatory effect of a low subhypnotic dose (10 mg/kg) or the posthypnotic hyperactivity. This suggests a negligible involvement of opioid mechanisms in the hyperactivity induced by pentobarbital.

Animals↗
PubMed1989

Suppression of pentobarbitone-induced hyperactivity by past experience in mice.

Locomotor activity of CD-1 mice, tested in an unfamiliar environment (toggle-floor box), was increased either by a subhypnotic dose (20 mg kg-1) of pentobarbitone or after recovery from pentobarbitone-induced (50 mg kg-1) anaesthesia. On the contrary, when mice were tested 6 h after a single exposure to the apparatus, pentobarbitone in either case failed to produce hyperactivity. The results demonstrate that mice recovering from barbiturate anaesthesia maintain susceptibility to the exteroceptive stimuli provided by a novel environment and knowledge of the environment acquired during past experience.

Anesthesia↗
PubMed1988

Reserpinization enhances electroconvulsive treatment effects on cortical alpha 1-adrenoceptors.

Repeated electroconvulsion shock (ECS) for 7 days given to mildly reserpinized rats strongly elevated the density of [3H]prazosin-labelled alpha 1-adrenoceptors and depressed the EC50 for norepinephrine-stimulated inositol phosphate accumulation, while the effects of either treatment given alone were small or negligible. Alterations in alpha 1-adrenoceptor activity caused by ECS could possibly be a function of receptor sensitivity during drug treatment.

Animals↗
PubMed1988

The influence of electroshock on adrenoceptor function in rat brain cerebral cortex: selectivity for the alpha-adrenoceptor site.

The present study was undertaken to examine the effect of electroshock on adrenoceptor-mediated cAMP and inositol phosphate accumulation in rat brain cerebral cortical slices. Under the conditions of these experiments, isoproterenol-induced cAMP accumulation was unaltered by electroshock, although there was a significant reduction in the norepinephrine- and isoproterenol + 6-fluoronorepinephrine-stimulated responses. No change in alpha-adrenoceptor-mediated inositol phosphate accumulation was noted. The results indicate that electroshock selectively modifies an alpha-adrenoceptor system in brain that differs from that associated with inositol phosphate accumulation.

Animals↗
PubMed1988

Effect of naloxone on the locomotor stimulatory action of chlordiazepoxide in mice.

Locomotor activity was measured, during 60 min, in CD-1 mice receiving chlordiazepoxide (2.5 or 5 mg/kg) after a pretreatment with saline solution or naloxone (0.5, 1, 2.5 or 5 mg/kg). Both doses of chlordiazepoxide significantly increased locomotor activity in saline-pretreated mice. Naloxone prevented chlordiazepoxide-induced hyperactivity, at doses that did not themselves affect activity. This antagonistic action of naloxone indicates that opioid mechanisms are involved in the locomotor stimulatory effects exerted by chlordiazepoxide in mice.

Animals↗