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M R Dzoljic

Publications and source records attributed to M R Dzoljic.

At least 19 recordsLinked to original sources
PubMed1992

5-HT1-like receptor agonists enhance wakefulness.

The effects of four 5-HT1-like receptor agonists (8-OH-DPAT, RU 24969, BEA 1654 and 5-carboxamidotryptamine) and some putative 5-HT1-like receptor antagonists on vigilance were examined in an attempt to clarify the role of 5-HT1-like receptors in the sleep-waking pattern of rats. Both 8-OH-DPAT (0.5-2.0 mg/kg, s.c.) and RU 24969 (0.5-2.0 mg/kg, s.c.) increased wakefulness and the latencies of slow wave and rapid eye movement (REM) sleep. The slow wave and REM sleep were correspondingly decreased or completely abolished. The two other 5-HT1-like receptor agonists had either a slight (BEA 1654, 1.0-5.0 mg/kg, s.c.) or no (5-carboxamidotryptamine, 0.5-2.0 mg/kg, s.c.) effect on sleep pattern. The arousal effect of 8-OH-DPAT was further potentiated in rats pretreated with reserpine (2.5 mg/kg, i.p.; 18 hr before 8-OH-DPAT). The non-selective 5-HT1-like and 5-HT2 receptor antagonist, methiothepin (2.0 mg/kg, i.p.) and the beta-adrenoceptor antagonist propranolol (16.0 mg/kg, s.c.), which is a putative antagonist at 5-HT1A and 5-HT1B receptor subtypes, significantly potentiated the arousal effect of RU 24969. The putative 5-HT1A and 5-HT1B receptor antagonist, cyanopinolol (4.0 mg/kg, s.c.), mixed 5-HT1A receptor agonist/antagonist MDL 72832 (1.0 mg/kg, s.c.) and the alpha 1-adrenoceptor antagonist prazosin (2.0 mg/kg) did not affect the vigilance, altered by RU 24969. These results suggest that the arousal effect of 5-HT1-like receptor agonists is probably not mediated by any of the subtypes of 5-HT1-like receptors or by an activation of a noradrenergic system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

The effects of orally active enkephalinase inhibitors on morphine withdrawal syndrome.

Considerable evidence has accumulated to suggest that intracerebroventricular administration of enkephalinase inhibitors, which do not penetrate the blood-brain barrier, significantly attenuates opioid withdrawal syndrome. Therefore, the aim of this study was to examine the effect of intraperitoneal (i.p.) administration of orally active enkephalinase inhibitors, acetorphan (2.5-20 mg kg-1) and SCH 34826 (15-120 mg kg-1). These drugs significantly decreased the severity of the naloxone precipitated withdrawal syndrome in morphine dependent rats and mice. It therefore appears that these orally active enkephalinase inhibitors are promising tools in studying modulation of opioid dependence phenomena.

Administration, Oral↗
PubMed1991

Sleeping with and without norepinephrine: effects of metoclopramide and D,L-threo-3,4-dihydroxyphenylserine on sleep in dopamine beta-hydroxylase deficiency.

Sleep characteristics are presented for two female patients (aged 21 and 31 years) with central and peripheral dopamine beta-hydroxylase (DBH) deficiency. This deficiency results in the absence of norepinephrine, epinephrine, and their metabolites in plasma, urine, and cerebrospinal fluid, while concentrations of dopamine are increased. The sleep pattern of these patients was studied when they were untreated, after blockade of central dopamine receptors with metoclopramide, and after restoring norepinephrine production with D,L-threo-3,4-dihydroxyphenylserine (DOPS). When the patients were untreated sleep duration was normal, with tendencies of a decreased amount of rapid eye movement (REM) sleep, presence of alpha-delta sleep, and an increased amount of slow-wave sleep. The amount of REM sleep varied between 18 and 21% of sleep period time. Administration of metoclopramide resulted in a slight reduction of REM sleep to 16-17%, whereas wakefulness after sleep onset increased. During treatment with DOPS, an increase in the amount of REM sleep was observed in both patients to an average amount of 27%. These data indicate that in patients with DBH deficiency norepinephrine is not essential for the development of a normal sleep/wake pattern but may have a facilitatory role in the generation of REM sleep.

Adult↗
PubMed1991

Decrease of beta-endorphin in the brain of rats following nitrous oxide withdrawal.

beta-Endorphin levels in the whole rat brain were not changed during acute (25 min) or chronic (48 h) exposure of rats to N2O. However, a significant decrease of beta-endorphin was found in the whole brain, brain stem and subcortex during the withdrawal from chronic exposure to N2O. It has been suggested that decrease of beta-endorphin levels during N2O withdrawal could be ascribed to unspecific stress accompanying drug withdrawal. Decrease of central beta-endorphin during N2O withdrawal might have a significant modulatory effect on transmitter balance, neuronal excitability and corresponding withdrawal behaviour. Furthermore, the decrease of beta-endorphin levels in the whole brain during N2O withdrawal might contribute to the postanaesthesia N2O-excitatory syndrome in humans. This might explain the known therapeutic effect of the opioid drug, meperidine on the excitatory N2O withdrawal phenomena during recovery from N2O anaesthesia in man.

Animals↗
PubMed1987

Enhanced prostaglandin E2 and thromboxane B2 release from resident peritoneal macrophages isolated from morphine-dependent rats.

Resident peritoneal macrophages from morphine-addicted rats (4 days) released more prostaglandin (PG) E2 and thromboxane (Tx) B2, but not 6-keto-PGF1 alpha, than cells from control animals. This effect, which was due to an enhancement of endogenous AA turnover, was not related to any changes in cAMP synthesis or lysosomal enzyme secretion. [D-Ala2]-Met-enkephalin had no effect on eicosanoid release in vitro. Both morphine and PGE2 have been shown to depress macrophage functions. We suggest that morphine-stimulated macrophage PGE2 synthesis, and the consequent inhibition of phagocytosis, could contribute to the decreased resistance to infections associated with opiate addiction.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Inhibition of enkephalinase activity attenuates naloxone-precipitated withdrawal symptoms.

In this study we examined the effects of the enkephalinase inhibitor, thiorphan, on the naloxone-precipitated withdrawal syndrome in chronic morphine dependent rats. Intracerebroventricular administration of thiorphan (40 micrograms/2 microliter) in morphine dependent rats, inhibited the severity of the naloxone-precipitated abstinential syndrome. Administration of thiorphan (20 micrograms/0.5 microliter) in the periaqueductal grey matter of morphine dependent rats, in addition to explosive motor behaviour and ipsilateral rotation, also significantly suppressed most of the naloxone-precipitated withdrawal symptoms. It is suggested that a decreased biotransformation of endogenous opioid peptides might replace the relative shortage of morphine during withdrawal in opiate addicted subjects and attenuate the abstinence symptoms.

Amino Acids, Sulfur↗
PubMed1987

Phelorphan, an inhibitor of enzymes involved in the biodegradation of enkephalins, affected the withdrawal symptoms in chronic morphine-dependent rats.

Intracerebroventricular administration of phelorphan (158 nmol/2 microliters), a blocker of dipeptidylaminopeptidase (enkephalinase B) and other enzymes involved in the enkephalin biodegradation, inhibited in chronic morphine-dependent rats, the occurrence of some of the naloxone-precipitated withdrawal symptoms. This effect of phelorphan was compared with an equimolar dose of the dipeptidyl-carboxypeptidase inhibitor (enkephalinase A), thiorphan. The results indicate that both drugs decrease some of the naloxone-precipitated withdrawal symptoms (writhing, digging, head hiding, chewing, diarrhoea and Straub tail), while others were potentiated (penile licking) or unaltered (wet dog shakes, grooming and rearing). In addition, phelorphan compared with the controls or thiorphan, pretreated animals, increased the frequency of paw tremor, head shakes, scratching, erection and ejaculation, but other symptoms were decreased (stretching) or unaltered (teeth chattering). The results are discussed in light of the differences in permeability and specificity of the two enkephalinase inhibitors. Furthermore, these data support the hypothesis that the use of enkephalinase inhibitors might be a promising way for the attenuation of the severity of the withdrawal syndrome.

Aminopeptidases↗
PubMed1987

Effects of delta opioid antagonists on enkephalin-induced seizures.

We examined the effect of opioid receptor antagonists on the seizure phenomena induced by specific delta opioid receptor agonist [D-Ser2,Leu5] enkephalyl-Thr (DSLET). The experiments have been performed in the anesthetized rats, and the DSLET-induced seizure phenomena were registered by electrocorticogram and electromyogram. It was demonstrated that two selective delta opioid receptor antagonists, ICI 152,129 and ICI 174,864 inhibited DSLET-induced epileptiform ECoG pattern and myoclonic contractions in a dose-related manner. An equimolar concentration of naloxone failed to antagonize the epileptiform effects of DSLET. It is concluded that delta opioid receptor agonist-induced seizure is mediated by delta receptors, since it can be blocked by delta opioid receptor antagonists. Evidently, delta opioid antagonists can be used as a good tool, in order to demonstrate a delta component in the seizure phenomena induced by other endogenous opioid peptides or their derivatives.

Animals↗
PubMed1986

Regional cerebral blood flow during enkephalin-induced seizures in the rat.

Blood flow, determined by the radioactive microsphere technique during epileptiform seizures induced by [D-Ser2,Leu5]enkephalyl-Thr (DSLET), a specific delta-opioid receptor agonist, was examined in different areas of the brain of the rat at various time intervals. An increase in blood flow to the hippocampus and brain stem was observed 2.5 min after administration of DSLET into the left lateral ventricle. An additional increase in flow occurred in the striatum and cerebellum 2.5 min later (5 min after the injection), at which time both the neural and vascular effects of the drug were most marked. Ten minutes after the administration of the drug, cerebral blood flow in all regions except the hippocampus, returned to the respective baseline values. Since the time-course and the magnitude of functional activity and blood flow in the hippocampus showed a good correlation, it is suggested that this region of the brain may play an essential role in triggering and maintaining the seizure phenomena induced by enkephalin.

Animals↗
PubMed1986

REM sleep deprivation antagonizes morphine-induced akinesia and catalepsy.

An examination was made of the effect of REM sleep deprivation (REMSD) on some forms of altered motor activity, such as akinesia and catalepsy, induced by intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of morphine in adult, male Wistar rats. Administration of morphine (25 mg/kg i.p.) induced an akinetic-cataleptic syndrome and decreased spontaneous vertical motor activity (SVMA) in animals allowed undisturbed sleep. REMSD decreased the morphine-induced akinesia and catalepsy that are known to be mediated by an inhibitory mu-opiate system. The locomotor depressant action of morphine was converted to excitation (manifested as increased SVMA and hopping behavior) by REMSD. Similarly, decreased motor activity following i.c.v. administration of morphine (25 micrograms) was replaced by excitation in the form of jumping behavior after REMSD. Naltrexone (1 mg/kg i.p.) blocked the akinetic and cataleptic effects, but not the excitatory effects, of morphine. It is suggested that REMSD is associated with a functional insufficiency of an inhibitory mu-opiate system, thus unmasking the excitatory morphine effects. The proposed insufficiency of an endogenous opioid system might explain an increase in neuronal excitation during REMSD and the therapeutic effect of REM deficiency in some types of depression.

Animals↗
PubMed1986

Enkephalinase inhibitors attenuate naloxone-precipitated withdrawal syndrome.

Enkephalinase inhibitors phosphoramidon, thiorphan or phelorphan suppressed naloxone-precipitated withdrawal symptoms in acute and chronic morphine dependent mice and rats. It is suggested that decreased biotransformation of the endogenous opioid peptides might compensate the relative shortage of exogenous opiates during withdrawal in opiate dependent subjects and could be a new and promising way to attenuate the severity of abstinential syndrome.

Amino Acids, Sulfur↗
PubMed1986

Enkephalinase inhibition suppresses naloxone-induced jumping in morphine-dependent mice.

The effect of the enkephalinase inhibitor phosphoramidon on the withdrawal syndrome following acute and chronic morphine-induced physical dependence in mice, was investigated. Phosphoramidon administered intracerebroventricularly (50-200 micrograms) suppressed significantly the naloxone-precipitated withdrawal jumping and wet dog shakes while forelimb shakes were potentiated in both acute and chronic morphine-dependent mice. It is suggested that increased saturation of the opioid receptors by endogenous opioid peptides following enkephalinase inhibition, might suppress the severity of the withdrawal syndrome.

Animals↗
PubMed1979

Enkephalin-induced myoclonic twitches blocked by ergometrine and potentiated by haloperidol.

Myoclonic twitches (MT) in the submandibular muscles induced by intraventricular administration of D-ala2-met-enkephalinamide (DALA) were studied electromyographically in the rat. Measurement of MT activity was selected since it permits parallel study of the effect of enkephalin on both dopaminergic and serotonergic transmitter systems. The twitches induced by enkephalin were blocked by naloxone, gamma-hydroxybutyrate, and ergometrine, but potentiated by haloperidol. Methysergide did not alter the stimulatory effect of DALA. These results were interpreted as a possibility for a specific enkephalin-induced activation of the so-called inhibition-mediating dopaminergic system, which is sensitive to the blocking action of ergometrine, but resistant to the blocking action of haloperidol.

Animals↗
PubMed1978

Prostaglandins and sleep. Awaking effect of prostaglandins and sleep pattern of essential fatty acids deficient (EFAD) rats.

The experiments were carried out to investigate the effects of prostaglandins (PGs) on the sleep pattern in the cat, and in normal and EFAD rats. The data indicate that the duration of slow wave sleep (SWS) was significantly longer in EFAD rats compared with the normal rats. However, no difference in the REM sleep was observed between the two groups. Intraventricular (i.vc. )administration of PGE1, PGE2 and PGF2alpha increased wakefulness without a significant alteration of REM sleep. PGE1 administered i.vc. did not alter the duration of SWS or REM sleep in the chronic cat, but induced ponto-geniculo-occipital (PGO) waves (spikes) which are the phasic phenomenon of REM sleep. The fact that previous administration of 5-hydroxytryptophane abolished the PGE1-induced PGO spiking, might indicate that this drug triggered the spikes mainly via the functional inhibition of the serotonergic system.

5-Hydroxytryptophan↗