Combination of phenobarbital with phenytoin and pregabalin produces synergy in the mouse tonic-clonic seizure model: An isobolographic analysis.

Aims: Despite many antiepileptic drugs (AEDs) are available to treat epilepsy, there is still about 30% of epilepsy patients inadequately treated with these AEDs. For these patients, polytherapy with two or three AEDs to fully control their seizure attacks is recommended. Unfortunately, polytherapy is always associated with drug interactions, whose nature may be beneficial, neutral or unfavorable.

Different pattern of changes in calcium binding proteins immunoreactivity in the medial prefrontal cortex of rats exposed to stress models of depression.

Reductions in the number and size of neurons in the medial prefrontal cortex (mPFC) have been documented in many post-mortem studies of depressed patients and animals exposed to stress. Here, we examined the effect of chronic unpredictable stress (CUS) and chronic mild stress (CMS) on specific populations of neurons in the rat mPFC. Antibodies directed against parvalbumin (PV), calbindin D-28K (CB) and active caspase-3 have been used to quantify the numerical density of PV-immunoreactive (PV-ir), CB-ir and active caspase-3-ir cells, and to measure the relative optical density of neuropil.

Chronic unpredictable stress-induced reduction in the hippocampal brain-derived neurotrophic factor (BDNF) gene expression is antagonized by zinc treatment.

Preclinical data indicate the antidepressant activity of zinc and the involvement of the brain-derived neurotrophic factor (BDNF) in this mechanism. The present study investigates the effect of chronic (16 days) combined treatment with zinc (15 mg/kg zinc hydroaspartate) and imipramine (5 mg/kg) in chronic unpredictable stress (CUS) on the BDNF mRNA level in the rat brain. Moreover, serum zinc concentrations were also assessed.

Alterations in hippocampal calcium-binding neurons induced by stress models of depression: a preliminary assessment.

In this study, the neuropathological changes induced by chronic unpredictable stress (CUS) and chronic mild stress (CMS) in calbindin D-28K (CB) and parvalbumin (PV) immunoreactive neurons in the rat hippocampus were demonstrated. We used immunohistochemical techniques to quantify the numerical density and morphological changes of PV immunoreactive and CB immunoreactive neurons in the dentate gyrus (DG) and the CA1 and CA3 regions of the hippocampus. We also assessed cell proliferation (Ki-67) and apoptotic processes (active caspase-3) in the DG.

Influence of zinc supplementation on imipramine effect in a chronic unpredictable stress (CUS) model in rats.

Zinc is an endogenous modulator of neuronal activity and may play an important role in the pathogenesis of depression. Recent studies have shown that zinc exhibits antidepressant-like activity in some models of depression in rodents. Our previous studies have shown that the footshock-induced fighting behavior was reduced in the rats subjected to chronic unpredictable stress (CUS).

Histological examination of the kidney after experimental administration of MK-801 and dexamethasone.

The aim of the research was histological assessment of the influence of MK-801 (NMDA receptor antagonist) and dexamethasone on the kidney. The experiment was carried out on adult Albino-Swiss mouse males. MK-801 was administered in the dose of 0.

Effect of NMDA receptor antagonists on behavioral impairment induced by chronic treatment with dexamethasone.

Severe and prolonged stress but also long-term treatment with glucocorticoids (GCs) have been described to cause brain damage (especially hippocampal and striatal neurons) in humans as well as in animals. GCs potentiate stress or ischemia-induced accumulation of excitatory amino acids (EAA) in the extracellular space of the hippocampus. It was shown that EAA play a major role in various neurologic disorders with cognitive dysfunction.

Effect of chronic treatment with dexamethasone on brain dopamine receptors in mice.

Glucocorticoids are expressed in the central nervous system. Radioligand binding studies have shown their presence in the neurons of the limbic system, a structure involved in mood control and subtle regulation of hypothalamic-pituitary-adrenal (HPA) axis. Structures of the limbic system are also rich in dopaminergic innervation.

Antidepressants in chronic unpredictable mild stress (CUMS)-induced deficit of fighting behavior.

Chronic unpredictable stress (CUS) is one of the behavioral models resembling in some respects (loss of normal aggresiveness) human depression. In the present study, consistent with the ethical principles for scientific experiments on animals, we have decided to modify the CUS procedure. In this new modified model named chronic unpredictable mild stress (CUMS), we have introduced mild stressor (14 h period of 45 degrees cage tilt) instead of one severe stressor (20 s exposure to electric footshock).

Repeated treatment with selective serotonin reuptake inhibitors but not anxiolytics prevents the stress-induced deficit of fighting behavior.

Several animal models of "depression" have been examined. One of them is chronic unpredictable stress (CUS)-induced deficit of fighting behavior in rats. In the present study, we compared the effects of two antidepressants (fluoxetine or fluvoxamine) and three anxiolytics (buspirone, lorazepam or oxazepam) on the electric footshock-induced fighting behavior in the pairs of male Wistar rats exposed to CUS procedure (16-day application of various unpredictable stressors).

Effect of imipramine on brain D-1 and 5-HT-2A receptors in a chronic unpredictable stress model in rats.

Chronic unpredictable stress (CUS) model of depression is one of the well validated animal models of depression. In this paper, we report the results of investigations into dopaminergic D-1 and serotonergic 5-HT-2A receptors in the brain of rats subjected to CUS procedure and treated chronically with imipramine. We have examined the dopaminergic D-1 ([3H-SCH 23390) in the limbic area and serotonergic 5-HT-2A ([3H-ketanserin) receptors in the cerebral cortex by a saturation radioligand binding method in rats subjected to CUS paradigm, imipramine, both CUS and imipramine and control animals.

Glucocorticoids modulate behavioral effects induced by dopaminergic agonists in rats.

Studies showing the presence of glucocorticoids, and their binding sites in the central nervous system indicate that these hormones may affect central neurotransmission. Both, dopaminergic brain system and glucocorticoids are considered to be involved in certain psychopathological conditions in humans, including depression, addiction or schizophrenia. The present study aimed to investigate the influence of glucocorticoids on dopamine agonists-induced stereotyped behavior and locomotor hyperactivity in rats.

Brain monoamine receptors in a chronic unpredictable stress model in rats.

Antidepressant drugs are devoid of mood-elevating effects in normal (non-depressed) human subjects, thus, it is necessary to evaluate the antidepressant property of compounds (drugs) in animal models of depression. Several animal models of depression have been introduced, however, only a few have been extensively validated. In the present study we report the results of investigations into monoaminergic receptors in the brain of rats subjected to chronic unpredictable stress (CUS) procedure (one of the well validated animal models of depression).

Reversal of stress-induced deficit in aggression by monoamine oxidase inhibitors.

In the present study we investigated the effect of two monoamine oxidase (MAO) inhibitors: moclobemide (selective, reversible inhibitor of MAO-type A) or selegiline (selective irreversible inhibitor of MAO-type B) on electric footshock-induced fighting behavior in normal (unstressed) and chronically stressed (14 various stressors over 16 days) rats. In rats exposed to chronic stress the number of fighting attacks was reduced by about 75%. Prolonged (once a day, for 14 days) treatment with moclobemide (50 mg/kg/day) or selegiline (2 mg/kg/day) counteracted the deficit in aggression induced by chronic stress.

Strychnine-insensitive glycine/NMDA sites are altered in two stress models of depression.

Chronic severe stress (CSS) and chronic mild stress (CMS) affect the properties of [3H]5,7-dichlorokynurenic acid (5,7-DCKA) binding to strychnine-insensitive glycine/NMDA sites in the rat cerebral cortex. Specifically, CSS decreases, while CMS increases, the potency of glycine to displace [3H]5,7-DCKA binding to glycine/NMDA sites. Moreover, in both models, a reduction of the specific [3H]5,7-DCKA binding was observed.

GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride] and the anticonvulsive activity of conventional antiepileptics against pentetrazol in mice.

Excitatory amino acids participate in the generation of seizure activity. Consequently, the effects of GYKI 52466 [1-(4-aminophenyl)-4-methoxy-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride], an antagonist of glutamate-mediated events, on the protective activity of conventional antiepileptic drugs against pentetrazol were studied. GYKI 52466 (up to 10 mg/kg, i.

Prolonged treatment with beta-adrenoceptor antagonists counteracts the aggression deficit induced by chronic stress.

Chronic stress-induced behavioral disturbances have been used as experimental models of depression. One of them is the deficit of fighting behavior induced by 16-day application of various unpredictable stressors. In the present study we investigated the effect of beta-adrenoceptor antagonists (propranolol, pindolol, nadolol and acebutolol) on electric footshock-induced fighting behavior in chronically stressed (14 various stressors over 16 days) male Wistar rats.

ACTH 4-9 analogue facilitates the antiimmobility effect of antidepressants and dopamine agonists in swimming rats.

Evidence exists that the 4-10 or 4-9 fragments of adrenocorticotropic hormone (ACTH) produce some behavioral effects in animals and in humans. The present study was designed to investigate whether ACTH 4-9 interferes with the effects of antidepressants: fluoxetine (FLU), fluvoxamine (FOX), selegiline (SEL) or dopamine agonists: piribedil (PRB) or quinpirol (QPR) in forced swimming test and in open field in rats. ACTH 4-9 was given in a single dose (25, 50 or 100 micrograms/kg) or for 7 days (50 micrograms/kg/day), alone or together with antidepressants or dopamine agonists.

The effect of NMDA antagonists on footshock-induced fighting behavior in chronically stressed rats.

In the present study we investigated the effect of two non-competitive antagonists of N-methyl-D-aspartate (NMDA) subtype of glutamate receptor: memantine (2.5 mg/kg) or MK-801 (0.1 mg/kg) on electric footshock-induced fighting behavior in normal (unstressed) and chronically (14 various stressors over 16 days) stressed rats.

Acute effect of dopamine agonists and some antidepressants in stress-induced deficit of fighting behavior.

The effect of dopamine (DA) agonists (apomorphine, quinpirole) and three antidepressants (selegiline, nomifensine, imipramine), given in a single dose, on the electric footshock-induced fighting behavior was investigated in the control and chronically stressed rats. It was found that 48 h after the last session of chronic stress (various stressors applied for 16 days) the number of shock-induced fighting attacks was reduced by 50-70% in comparison with the control value. The drugs (except for imipramine), given in a single dose, 48 h after the last session of chronic stress, increased the number of fighting attacks and restored it to the control or above the control value.

The effect of calcium channel antagonists on the aggressive behavior in chronically stressed rats.

The influence of some calcium channel antagonists (CaChaA): nifedipine (NIF), nimodipine (NIM), nitrendipine (NITR), cinnarizine (CIN), and flunarizine (FLU) on electric footshock-induced aggressive behavior was investigated in chronically stressed rats. It was found that chronic stress (various stressors over 16 days) reduced the number of fighting attacks (by about 50%) without changing the pain reactivity of rats. The CaChaA given in a single dose (5 mg/kg ip) did not influence the intensity of fighting.

The influence of antidepressants on aggressive behavior in stressed rats: the role of dopamine.

The influence of dopamine (DA) receptor blockers (haloperidol, sulpiride) on electric footshock-induced fighting behavior and on the effect of antidepressants (imipramine, clomipramine, nomifensine, mianserine) was investigated in chronically stressed male Wistar rats. Exploratory activity in an open field was measured in the same groups of animals. The effect of chronic stress and antidepressants on DA utilization in the brain was also investigated.

Chronic stress reduces fighting behavior of rats: the effect of antidepressants.

The effect of chronic stress (14 various unpredictable stressors over 16 days) on electric footshock-induced fighting behavior of pairs of male Wistar rats was studied. The influence of antidepressant drugs (imipramine, desmethylimipramine, nomifensine, clomipramine, mianserine and doxepine) administered chronically (1 h before the stressor) on the aggressive behavior was also investigated in control and in stressed rats. Moreover, the effect of chronic stress on noradrenaline (NA) utilization in the brain was estimated in control and in antidepressant-treated rats.

[Morphologic and toxicologic evaluation of response to subcutaneous para-osseous implants Medpol-1 and Medpol-2 in rats].

Cobalt alloys produced in Poland and meant for orthopedic implants were morphologically and toxicologically evaluated. They were implanted subcutaneously in the para-osseous region of rats' heads. The results of the experimental tests strongly suggest the advisability of a clinical research project (study) on the examined cobalt alloys: Medpol-1 and Medpol-2.