Biomedical subjects

J Vetulani

Publications and source records attributed to J Vetulani.

At least 37 records · Page 2Linked to original sources

PubMed1996

Different effects of chronic administration of haloperidol and pimozide on dopamine metabolism in the rat brain.

We investigated the differences between the action of haloperidol and pimozide on dopamine metabolism and on catalepsy in periods up to 6 weeks after cessation of chronic administration of the neuroleptics to male Wistar rats. Dopamine and its metabolites (dihydroxyphenylacetic and homovanillic acids) were measured, using high-performance liquid chromatography (HPLC), in the frontal cortex, nucleus accumbens, and striatum. Both neuroleptics produced similar effects after a single dose: catalepsy and an increase of dopamine metabolism in the brain structures. However, haloperidol and pimozide differed after chronic treatment. In haloperidol-treated rats hypersensitivity of the dopaminergic system developed at the end of 2 weeks' administration, as evidenced by depression of dopamine metabolism. The biochemical changes were accompanied by behavioral hyperactivity that lasted up to 3 weeks. Dopamine metabolism in rats treated with pimozide was normal from 24 h after the end of the treatment, while catalepsy was maintained at the high level for up to 8 days and was observable up to 3 weeks after the last dose. Our results suggest that in contrast to haloperidol, pimozide is not able to produce adaptive changes leading to supersensitivity of the dopaminergic system. This may be the consequence of its potent Ca2+ channel blocking action.

Animals↗

PubMed1996

Facilitation and attenuation of social recognition in rats by different oxytocin-related peptides.

The memory-modulating effects of subcutaneously administered oxytocin and related peptides were investigated in the social recognition paradigm in rats. The attenuation of social recognition by 0.6 and 6 micrograms/kg of oxytocin was mimicked by the same doses of des-Gly8-oxytocin, [pGlu4, Cyt6]oxytocin-(4-9) and prolyl-leucyl-glycinamide (PLG) and by 0.6 micrograms/kg of oxytocin-(1-6) and [pGlu4,Cyt6]oxytocin-(4-8). The peptide leucyl-glycinamide (LG) was not active in this respect. The facilitation of social recognition by 0.6 and 6 ng/kg of oxytocin was mimicked by the same doses of PLG and LG but not by the other peptides and the amino acid glycine. It is concluded that the active moieties for attenuation and facilitation of social memory reside in different parts of the oxytocin molecule, e.g. the 5-7 and 8-9 region, respectively.

Animals↗

PubMed1996

The effect of chronic administration of amitriptyline on the effects of subsequent electroconvulsive treatment on responsiveness of alpha 1-and beta-adrenoceptors in the rat cortical slices.

Both antidepressant drugs and repeated electroconvulsive shock (ECS) produce adaptive changes in cerebral neurotransmitter systems. As in the clinical practice ECS is used almost always after therapeutical failure of pharmacotherapy, we investigated presently how chronic administration of an antidepressant amitriptyline affects the action of subsequent multiple ECS in rats. Amitriptyline differed from ECS and from other classical antidepressant in producing no beta-downregulation and potentiating the inhibitory effect of protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA), on responses of alpha 1-adrenoceptor system to noradrenaline. The action of ECS on alpha 1-adrenoceptor system remained essentially unaffected by previous amitriptyline administration. Its downregulatory effect on responses of beta-adrenoceptor system to noradrenaline, and particularly to isoproterenol, were attenuated by previous drug treatment. The present results suggest that previous chronic administration of antidepressant drugs may alter the effect of subsequent ECS.

Adrenergic alpha-1 Receptor Agonists↗

PubMed1996

Differences in effects of Ca2+ channel antagonists on dopamine metabolism in the limbic and extrapyramidal dopaminergic structures.

The effect of single and multiple administration of Ca2+ channel antagonists, nifedipine and verapamil, on concentrations of dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), was investigated in the mesolimbic (cortex, nucleus accumbens) and extrapyramidal (striatum) structures in Wistar rats. A single dose of nifedipine (10 mg/kg IP) produced some activation of the dopaminergic system in both cortex (increase in DOPAC) and n. accumbens (increase in HVA); verapamil (20 mg/kg IP) produced an increase in HVA in the cortex only. Chronic treatment with either Ca2+ channel antagonist produced more marked activation of dopamine metabolism in the cortex and nucleus accumbens. Those changes were most expressed 1 h after the last treatment, but lasted for at least 24 h. No changes in dopamine metabolism were observed in the striatum. The present data suggest that Ca2+ channel antagonists after chronic treatment specifically activate the dopaminergic system in limbic structures.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1995

Differences between haloperidol- and pimozide-induced withdrawal syndrome: a role for Ca2+ channels.

We investigated the behavioral and biochemical events appearing in rats after withdrawal for 24 h or 8-12 days from two classical neuroleptics, haloperidol and pimozide. The neuroleptics were given for 14 days alone or shortly after injection of the Ca2+ channel blocker nifedipine. We have found that withdrawal effects after haloperidol and pimozide were different. After haloperidol treatment we observed an increase in cortical Ca2+ channel and limbic dopamine D1 receptor density and an increase in spontaneous motor activity and apomorphine-induced hyperactivity and stereotypy. In contrast no biochemical changes were observed during pimozide withdrawal, and locomotor activity and responses to apomorphine were depressed. Co-administration of nifedipine with haloperidol prevented the observed biochemical and behavioral symptoms of withdrawal. Nifedipine administration did not change the depressant effects of pimozide. Our results suggest that the voltage-dependent Ca2+ channel is involved in the observed withdrawal syndrome of neuroleptics, and that the absence of this syndrome after pimozide may be related to its considerable Ca2+ channel-blocking properties.

Animals↗

PubMed1994

Reversal by imipramine of beta-adrenoceptor up-regulation induced in a chronic mild stress model of depression.

Male Wistar rats were subjected to a chronic mild stress procedure involving different stress stimuli applied for 8 weeks. During this time the consumption of 1% sucrose solution was monitored at weekly intervals. After the first 3 weeks, when stressed animals displayed a reduction of sucrose consumption, the control and stressed groups were divided into subgroups receiving daily placebo or imipramine (10 mg/kg/day) treatment. After 5 weeks of treatment, 24 h after the last injection, the rats were killed and beta-adrenoceptor density and affinity in cortical membrane preparations and the accumulation of cyclic AMP in cortical slices stimulated with noradrenaline were assessed. While in stressed placebo-treated rats the sucrose consumption remained reduced, in the imipramine-treated group the level of consumption gradually returned to control values. The stressed placebo-treated rats also displayed an increase in cortical beta-adrenoceptor density (by 34%) with no changes in affinity, and an increase (22%) in the cyclic AMP response to noradrenaline in cortical slices. Imipramine, which in non-stressed rats did not affect sucrose intake but depressed the beta-adrenoceptor density and the cyclic AMP response, reversed the stress-induced decrease in sucrose consumption and the increase in the beta-adrenoceptor density; at physiological noradrenaline concentrations it also reduced the enhanced cyclic AMP response. The results suggest that the chronic mild stress procedure produces behavioral and biochemical changes consistent with a realistic model of depression in animals.

Adenylyl Cyclases↗

PubMed1994

The effect of electroconvulsive shock and nifedipine on spatial learning and memory in rats.

Several traumatic events including brain contusion, electroconvulsive shock therapy, epileptic seizures and others, may cause short-term retrograde amnesia. In spite of much recent attention, pharmacological treatment of memory impairment has not been fully successful. In the present paper we report on the possible antiamnesic action of the L-type calcium channel blocker, nifedipine. Rats trained in the spatial memory task showed gradual improvement in the escape latency to find the submerged platform. After completion of the learning, they also showed a strong spatial bias toward the place that previously contained the target platform. Prolonged post-trial electroconvulsive shock induced memory impairment. The calcium channel blocker, previously reported as a "cognitive enhancer," given either before or after the learning trial revealed no antiamnesic effect. Nifedipine also does not exert any action when given alone. These results suggest that the drug may not have antiamnesic action on human memory disturbed by electroconvulsive therapy.

Animals↗

PubMed1994

Modification of effects of chronic electroconvulsive shock by voltage-dependent Ca2+ channel blockade with nifedipine.

A single electroconvulsive shock produced analgesia (expressed as prolongation of hot-plate latency) in Wistar rats 45 min after the shock. The analgesic action was prevented by administration of nifedipine, 5 mg/kg i.p., 15 min before the electroconvulsive shock, while nifedipine injection after electroconvulsive shock did not affect the analgesia significantly. At the same time single electroconvulsive shock counteracted the reduction of [3H]nitrendipine binding to cortical and hippocampal membranes from rats pretreated with nifedipine. Chronic administration of electroconvulsive shock (once daily for 8 days) produced hyperalgesia, augmented locomotor responses to low doses of apomorphine and upregulation of cortical (but not hippocampal) voltage-dependent Ca2+ channels (assessed from [3H]nitrendipine binding). In rats receiving electroconvulsive shock chronically, always 15 min after nifedipine injection, neither behavioral hyperresponsiveness nor Ca2+ channel upregulation was observed. The results suggest that the primary event in post-electroconvulsive shock analgesia depends on Ca2+ influx into neurons through voltage-dependent Ca2+ channels, and that given under conditions of Ca2+ channel blockade electroconvulsive shock is unable to trigger changes leading to Ca2+ channel upregulation, and this is possibly the reason for prevention of development of hyperalgesia and increased responsiveness to dopaminergic stimulation.

Animals↗

PubMed1994

Differential involvement of voltage-dependent calcium channels in apomorphine-induced hypermotility and stereotypy.

The involvement of the voltage-dependent calcium channel in behavioral effects of apomorphine was tested in naive rats and in animals which were morphine-abstinent or were subjected to chronic electroconvulsive treatment (ECS). In naive rats a calcium channel blocker, nifedipine, which by itself does not affect locomotor activity, inhibited the locomotor stimulation induced by apomorphine, while it facilitated stereotyped behavior. Morphine-abstinent and ECS-treated rats displayed elevated responsiveness to apomorphine, reflected by hypermotility and stereotyped behavior after a dose of 1 mg/kg IP that does not produce overt behavioral effects in naive animals. Nifedipine, 5 mg/kg IP, significantly reduced hypermotility produced by apomorphine in morphine abstinent or ECS-treated rats. The calcium channel blocker did not, however, antagonize enhanced stereotyped behavior. The results indicate that apomorphine hypermotility is controlled by dihydropyridine calcium channels and that enhancement of calcium channel density produced by morphine abstinence and by chronic ECS potentiates the hypermotility response. Calcium channels seem to be differently involved in control of apomorphine-induced hypermotility and stereotypy.

Animals↗

PubMed1994

Retrieval associated cholinergic activity and its inhibition by memory updating.

Both hippocampal cholinergic and glutamatergic systems are believed to be engaged in learning and memory. By measuring behavior and ex vivo second messenger inositol phosphate (IP) accumulation, we investigated biochemical responses of cholinergic receptors to retrieval and acquisition processes in rats trained in a spatial task. We report that in rats retrieving spatial information, carbachol--induced IP accumulation strongly and transiently increased above values observed in handled controls and rats acquiring new information, and that this increase was profoundly inhibited by N-methyl-D-aspartate (NMDA). These results suggest that memory retrieval, rather than formation of a memory trace, is related to increased responsiveness of the hippocampal cholinergic system, and that formation of a new memory trace, which updates long-term memory, inhibits this cholinergic activation, possibly by a learning-associated increase in NMDA receptor activation. Moreover, the present study shows that the distinction between acquisition and retrieval processes can be demonstrated on both a behavioral and biochemical level.

Analysis of Variance↗

PubMed1994

The effect of (-)-4-(2-hydroxy-3(N-isopropylamino)-propoxyimino)-cis-carane on basal and forskolin-stimulated accumulation of cyclic AMP in the cerebral cortical slices of the rat.

(-)-4-(2-Hydroxy-3(N-isopropylamino)-propoxyimino)-cis-carane++ +, a local anaesthetic and platelet aggregation inhibitor which is much more potent than lignocaine, facilitated forskolin-induced cyclic (c) AMP accumulation in cerebral cortical slices of the rat. Lignocaine was ineffective in this respect. It is hypothesized that a cAMP-related mechanism may be involved in increased efficacy of the compound.

Analysis of Variance↗

PubMed1994

The responsiveness of cerebral cortical adrenergic receptors after chronic administration of atypical antidepressant mianserin.

The aim of this study was to evaluate the effect of mianserin, a second generation tetracyclic antidepressant agent, on the receptors' and second messenger systems related to noradrenergic transmission in the cerebral cortex of the rat. In in vitro experiments we confirmed that mianserin binds with equal potency to alpha 1- and alpha 2-adrenoceptors and does not affect beta 1-adrenoceptors. It inhibited the noradrenaline-stimulated inositol phosphate accumulation and did not change the cyclic AMP responses to noradrenaline and isoproterenol. The drug attenuated the inhibitory action of PKC activator, TPA, on the noradrenergic response from alpha 1-adrenoceptor and the potentiating action of TPA on the cyclic AMP stimulated with noradrenaline and isoproterenol. In chronic experiments we have found that, in contrast to most antidepressants, chronic treatment with mianserin does not produce strong beta-downregulation, but increases the maximal inositol phosphate response from alpha 1-adrenoceptor. The results indicate that alpha 1-upregulation might be a characteristic of those efficient antidepressant drugs which do not produce a strong beta-downregulatory effect.

Animals↗

PubMed1993

Effects of excitatory amino acids on inositol phosphate accumulation in slices of the cerebral cortex of young and aged rats.

The effects of glutamate, NMDA and quisqualate on carbachol- and norepinephrine-elicited formation of inositol phosphate (IP) were evaluated in slices prepared from the cerebral cortex of 3- and 24-month Sprague-Dawley rats. Glutamate, NMDA, and quisqualate antagonized the IP response to carbachol in a concentration-dependent fashion. This antagonism was more pronounced in aged than in young rats, both for glutamate (IC5O 0.114 and 0.210 mM) and NMDA (IC5O 0.0029 and 0.127 mM), but not for quisqualate. Glutamate (but not NMDA) also antagonized in a concentration-dependent fashion the IP response to norepinephrine, IC50s were 0.061 and 0.126 mM for aged and young rats, respectively; quisqualate had an inhibitory effect only at 1 mM concentration in the two age-groups, while in aged rats some stimulatory effect was present at 0.1 mM concentration. Glutamate, NMDA and quisqualate (1 mM) did not affect basal IP accumulation in either young or aged rats; quisqualate, however, at 0.1 mM concentration had some stimulatory effect, more pronounced in aged rats. This effect was probably responsible for the biphasic effect of quisqualate in this age-group. The most important finding consists of the demonstration of an age-related increase in the inhibitory effects of NMDA on carbachol-induced IP accumulation. This implies an altered modulation of cholinergic post-receptor mechanisms by glutamatergic mechanisms.

Aging↗

PubMed1993

Facilitation of shuttle-box avoidance behaviour in mice treated with nifedipine in combination with amphetamine.

The dihydropyridine calcium channel antagonist nifedipine, tested in mice of CD-1, C57BL/6 and DBA/2 strains, at doses of 2.5, 5 and 10 mg/kg IP, had no significant effect on shuttle-box avoidance acquisition. Nifedipine also failed to affect performance retention in CD-1 mice subjected to a one-trial passive avoidance task (step-through). While ineffective alone, nifedipine strongly enhanced the shuttle-box avoidance facilitating action of amphetamine (1 and 2 mg/kg IP) in low performing CD-1 mice. The results indicate that although calcium channel blockers do not affect learning in avoidance paradigms in normal animals, they can interfere with the effects of other centrally acting drugs. Calcium antagonists might interfere with neuronal changes induced by amphetamine, but at present it is difficult to explain the strong avoidance facilitation produced by combinations of nifedipine and amphetamine. A possibility that the action of nifedipine on cerebral circulation is involved in the amphetamine-nifedipine interaction cannot be excluded.

Amphetamine↗

PubMed1993

Reduction of morphine dependence and potentiation of analgesia by chronic co-administration of nifedipine.

Nifedipine, 5 mg/kg IP, potentiated the morphine-induced analgesia measured in the hot-plate, but not in the tail-flick test. Further experiments were carried out using the hot-plate test only. Pretreatment with nifedipine partially restores the analgesic action of morphine in morphine-tolerant rats. Co-administration of nifedipine with morphine in a chronic experiment did not prevent the loss of morphine efficiency (an increase in latency of 44% was not significant) and did not prevent the debilitating effect of chronic morphine administration reflected by an inhibition of the body weight gain, but prevented naloxone-induced withdrawal syndrome (quantified by counting head shakes) in the test carried out 24 h after the injection of nifedipine, when the drug did not affect morphine analgesia. Chronic treatment with either morphine or nifedipine did not produce a significant increase in the density of [3H] naloxone or [3H]prazosin binding sites in the cortex and in the rest of the brain (measured 24 h after the last dose), but the combined treatment resulted in a significant increase in the cortical [3H]prazosin binding site density. The present results suggest that opiate tolerance and physical dependence may be separated by co-administration of nifedipine and suggest that the combined chronic treatment with morphine and nifedipine may increase the efficacy of morphine during chronic treatment and prevent development of abstinence.

Analgesics↗

PubMed1993

Enhancement of the responsiveness of cortical adrenergic receptors by chronic administration of the 5-hydroxytryptamine uptake inhibitor citalopram.

The aim of this study was to evaluate the effect of citalopram, a second generation antidepressant agent producing no beta-down-regulation, on the receptors and second messenger systems related to noradrenergic transmission in the cerebral cortex of the rat. We confirmed that citalopram does not bind to alpha 1-, alpha 2-, and beta 1-adrenoceptors, but we found that it attenuates the inhibitory action of the protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate, on the noradrenergic response from alpha 1-adrenoceptor. In contrast to most antidepressants, chronic treatment with citalopram does not produce beta-down-regulation, but increases the responses to noradrenaline from beta-adrenoceptors without increasing the beta 1-adrenoceptor density. Chronic treatment with citalopram also increases the maximal response from alpha 1-adrenoceptor. The results indicate that beta-down-regulation is not a necessary characteristic of an efficient antidepressant drug.

Adenylyl Cyclases↗

PubMed1992

Low doses of oxytocin facilitate social recognition in rats.

Social recognition of juveniles by adult male residents has been shown to be modulated by neurohypophyseal hormones. The decrease of social investigation behavior during a second encounter with the same juvenile serves as index for social recognition. In the present study it was found that low doses (0.09-6.0 ng.kg-1) of oxytocin (OXT) given subcutaneously dose dependently facilitated social recognition. The effect of OXT appeared specific, since no change in social investigation was found when a novel juvenile was tested during the second encounter. No disturbances of social recognition by the low doses of OXT could be detected, in contrast to higher doses of this hormone. Other neurohypophyseal hormones, vasopressin and vasotocin, did not facilitate social recognition when tested in the same range of low doses.

Animals↗

PubMed1992

Similar effects of nifedipine and hydralazine on anaesthesia and hypermotility induced by pentobarbitone in mice.

Nifedipine, a dihydropyridine calcium channel blocker, and hydralazine, a non-calcium channel antagonist vasodilatator, enhanced pentobarbitone-induced sleeping time and reversed locomotor hyperactivity induced by a subhypnotic dose of the barbiturate in mice. The similarity of the behavioural effects, exerted by nifedipine and hydralazine, suggest that haemodynamic factors may play an important role in the interaction of calcium channel antagonists with barbiturates.

Anesthesia↗