Krzysztof Kus

Influences of chronic venlafaxine, olanzapine and nicotine on the hippocampal and cortical concentrations of brain-derived neurotrophic factor (BDNF)

Brain-derived neurotrophic factor (BDNF) is a key neurotrophic factor in the brain. It plays an important role in the etiopathogenesis and pharmacotherapy of mental disorders, such as depression or schizophrenia. In recent years, studies have shown that cognitive processes, which are impaired in the course of mental disorders, significantly change BDNF levels in the brain. Administered to rats at a dose of 20 mg/kg (b.d. for 5 weeks), venlafaxine (VEN) increases BDNF levels in the hippocampus and cortex, compared to controls. Administered at a dose of 0.5 mg/kg (b.d. for 5 weeks), olanzapine (OLA) significantly increases BDNF levels in both the cortex and the hippocampus. Similarly, nicotine (NIC) administered at a dose of 0.2 mg/kg (b.d. for 5 weeks) increases BDNF concentrations in both the hippocampus and the cortex. Combined administration of NIC with VEN or OLA does not increase BDNF levels in the hippocampus or the cortex. Based on our study, it can be claimed that BDNF mediates behavioral responses only to drugs used individually and participates in the antidepressant and procognitive effects of the study compounds. BDNF also initiates plastic changes and modulation of synaptic activity in rat brains.

Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats

Recent research has suggested that cognitive disorders are a persistent trait of mental illnesses such as schizophrenia. Cognitive deficits in the course of schizophrenia may be due to the disease and/or drug therapy, especially with old-generation drugs. Several clinical experiments have indicated the beneficial effects of new-generation antipsychotics on cognitive processes in patients treated for mental disorders. Aripiprazole is a new, atypical antipsychotic with a unique mechanism of action, which may have positive effects on cognitive functions. The aim of this study was to investigate the effects of aripiprazole on spatial memory in the Morris water maze and antidepressant activity in the Porsolt test. In addition, we examined whether aripiprazole had any side effects in the chimney test. The behavioral tests showed that aripiprazole improved spatial memory in rats and had antidepressant and anxiolytic effects after a single treatment; however, aripiprazole impaired motor coordination after repeated administration. We concluded that aripiprazole could be an effective antipsychotic for the treatment of patients with schizophrenia or bipolar disorder who have associated anxiety and cognitive deficits.

The influence of tobacco smoke and nicotine on antidepressant and memory-improving effects of venlafaxine

In experimental and clinical studies, central nicotinic systems have been shown to play an important role in cognitive function. Nicotinic acetylcholine receptors also mediate the reinforcing properties of nicotine (NIC) in tobacco products. A variety of studies have shown that acute treatment with NIC or nicotinic agonists can improve working memory function. Moreover, it is known that the monoaminergic system plays an important role in memory function. And there is evidence suggesting that prolonged use of NIC may exert antidepressant action via nicotinic receptors. The purpose of this study was to investigate the interactions between a novel antidepressant, venlafaxine (VEN), a blocker of noradrenaline and 5–hydroxytryptamine reuptake sites, and pure NIC in the context of antidepressant and memory function in tobacco smoke exposed and nonexposed rats. The animals were subjected to Porsolts test for testing antidepressant activity and their memory function (spatial memory) was evaluated in the Morris Water Maze Test. In tobacco smoke non–exposed and exposed rats both single and chronic administration of VEN (20 mg/kg po) shortened immobility time. NIC (0.2 mg/kg sc) significantly reduced immobility time on the 1st, 7th and 14th test days in both non–exposed and exposed rats. Combined VEN–NIC treatment in tobacco smoke non–exposed rats reduced immobility too. This effect of the combination of drugs was significantly stronger as compared to the effects obtained after individual administration of VEN or NIC. In the group exposed to tobacco smoke, joint administration of VEN–NIC induced a significant reduction of immobility as compared to the control and NIC groups. In the Morris Water Maze Test single and chronic administration of VEN, lower values of escape latencies and lower numbers of crossed quadrants were noted in both exposed and non–exposed rats, which indicates improved performance. After administering NIC we could observe improvement of spatial memory in both the exposed and non–exposed group. A similar effect of improvement of spatial memory was observed after joint administration of VEN and NIC. The study results support the involvement of nicotinic systems in memory processes in rats. Memory improvement and antidepressant effects following joint administration of VEN and NIC may depend on nicotinic interactions with monoaminergic systems and VEN may represent a new therapeutic approach to smoking cessation.

Some behavioural effects of risperidone in rats: comparison with haloperidol.

Risperidone is a dopaminergic as well as a 5-HT2 antagonist. The drug was found to exert beneficial effects on both positive and negative symptoms of schizophrenia. Since recently, schizophrenia is regarded as a composite of not only positive and negative but also affective and cognitive symptoms, in this study the effects of risperidone compared with typical neuroleptic haloperidol, on affective and cognitive functions were investigated in rats (anxiolytic, antidepressive and memory tests). We found, that in contrast to haloperidol, risperidone had antidepressive, anxiolytic and memory enhancing effects. The results obtained correspond with favourable effects of risperidone on mood disturbances and cognitive functions of schizophrenic patients observed under clinical conditions.

Concomitant use of tramadol and venlafaxine – evaluation of antidepressant-like activity and other behavioral effects in rats

BACKGROUND The aim of this study was to evaluate antidepressant-like effect (Porsolt test), locomotor activity and motor coordination of joint administration of tramadol (TRM) and venlafaxine (VEN) in rats. METHODS The tests were performed on male Wistar rats after single and chronic treatment (7 and 14 days) with TRM intraperitoneally (ip) and VEN orally (po) administered once a day. The controls were given 0.5% carboxymethylcellulose (CMC) solution (0.5 ml per rat, ip and po). RESULTS It was found that combination of TRM (5 mg/kg ip) with VEN (20 mg/kg po) caused an increased antidepressant effect compared to TRM and VEN administered alone, with no effect on locomotor activity or motor coordination in rats, which may be of clinical significance. It was also observed that reduced time of active swimming of animals in Porsolt test with an increased dose (10 and 20 mg/kg) and time of administration (7 and 14 days) of TRM were correlated with a decreased locomotor activity in rats. It may indicate the development of tolerance to TRMs antidepressant effect in rats during chronic treatment with doses higher than 5 mg/kg. CONCLUSION It can be expected that combination of low doses of TRM and VEN could potentially be feasible and relatively safe in cases with acute pain with co-existing depression, however, further investigations are needed.

Influence of aripiprazole and olanzapine on behavioral dysfunctions of adolescent rats exposed to stress in perinatal period

BACKGROUND Schizophrenia is a group of mental disorders of unclear origin, affecting around 1% of global population, most commonly young people. Of various treatment methods, pharmacotherapy using atypical neuroleptics such as aripiprazole (ARI) and olanzapine (OLA) seems to be the most effective. The aim of this paper was to show that prenatal stress causes impairment of cognitive functions in adolescent rats. METHODS The effect of chronic stress used in pregnant rats and the use of drugs such as ARI (1.5 mg/kg) and OLA (0.5 mg/kg) were studied in the Morris Water Maze (spatial memory) and Porsolt test (antidepressant effect). RESULTS The behavioral tests showed that ARI improved spatial memory both in the non-stressed control group (NSCG) (after single and chronic treatment) and in the prenatally stressed group (PSG) (only in 14 and 21 days of treatment). An antidepressant effect was observed in the NSCG (only in 1 and 7 days) and the PSG (after single and chronic administration). OLA also showed memory improvement in the NSCG (chronic treatment - 14 and 21 days) and the PSG (all days of treatment) rats, but the antidepressant effect was noted only in single administration in both study groups (NSCG and PSG). CONCLUSION(S) Results suggest that ARI and OLA may prove effective in treating both schizophrenia and depression and may improve disturbed memory functions observed in these diseases.

The influence of aripiprazole, olanzapine and enriched environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats

BACKGROUND Cognitive function deficits caused by impaired neurogenesis of the brain structures are considered an important pathogenic factor in many neurological and mental diseases such as schizophrenia and depression. The aim of the study was to determine the effect of the enriched environment on cognitive functions and antidepressant-like effect of prenatally stressed rats. It was important to determine the effect of aripiprazole ARI and olanzapine OLA and clarify whether the enriched environment induces increases in brain derived neurothropic factor BDNF in the hippocampus in the prenatally stressed group (PSG) and non-stressed control group (NSCG). METHODS The effect of chronic stress applied to pregnant rats and the use of ARI (1.5mg/kg ip) and OLA (0.5mg/kg ip) were studied in the Morris water maze (MWM), Porsolt Forced swimming test (FST) and by determining BDNF levels. RESULTS The results indicated that enriched environment improved spatial memory and also had an antidepressant-like effect on prenatally stressed rats. ARI improved spatial memory both in the NSCG and PSG, while OLA caused memory improvement only in the PSG. Moreover, both ARI and OLA reduced immobility time in the NSCG and PSG. In PSG rats, BDNF decrease was observed while chronic treatment with ARI and OLA increased BDNF levels in the hippocampi of NSCG and PSG rats. CONCLUSION It has been confirmed that enriched environment improves spatial memory of animals, removes symptoms of stress, has an antidepressant-like effect, and that new neuroleptics, such as ARI or OLA, modulate these functions (increased BDNF).

Cognitive effects of GABAergic antiepileptic drugs.

Many patients undergoing long-term treatment of epilepsy complain of memory disorders, which entail worse quality of life. The risk factors generating memory disorders include: morphological brain damage, the duration and course of epileptic seizures (conscience disorders), the time of diagnosis (the risk is greater if epileptic seizures start early in life), drug resistance, the presence of interseizure changes in the EEG in the form of sharp-wave discharges or sharp spike-wave/ slow spike-wave complexes and improper pharmacotherapy (exceeding the admissible concentration of drugs in blood serum, polytherapy). GABAergic neurotransmission of older antiepileptic drugs (barbiturates, benzodiazepines) makes them particularly prone to produce modest, but statistically significant disruption of cognitive processes. This explains the search for new antiepileptic drugs that will improve, or at least not impair, cognitive functions. The improvement of cognitive functions by new generation antiepileptic drugs results, among others, from their non-GABAergic mechanisms: they influence the ion channels and glutaminergic transmission.

Concomitant use of carbamazepine and olanzapine and the effect on some behavioral functions in rats

As shown in clinical studies, combinations of first generation normothymics (carbamazepine - CBZ) with atypical neuroleptics (olanzapine - OLA) lead to improvements in approximately half of patients treated for relapses of bipolar affective disease. Our previous studies have shown OLA to have an antidepressant effect when administered at a dose of 0.5 mg/kg only upon single administration; the effect did not last throughout chronic administration, whereas CBZ administered at a dose of 30 mg/kg showed an antidepressant effect only after 7 days of administration. As shown in our previous studies, both OLA and CBZ improve memory in rats but only after chronic administration. The improved antidepressant effect of many drugs, including OLA and CBZ used in combined therapy - as observed in our clinic - as well as confirmed evidence of OLAs and CBZs positive effects on cognitive functions in humans and animals substantiated commencement of research on defining the effect of combined administration of OLA and CBZ on sedation (tested in a locomotor activity test), antidepressant effect (Porsolt test) and spatial memory (Morris test) in animals. The tests were performed on male Wistar rats. It was found that in combined administration of CBZ and OLA for 7 and 14 days, OLA would completely prevent the CBZs sedative effect. With combined administration of CBZ and OLA, both as a single dose and after prolonged treatment for 7 days, a significant reduction in immobility time was observed. Combined administration of CBZ and OLA did not improve memory in rats that received these drugs in a single dose, whereas statistically significant differences were observed in the chronic experiments. It can be assumed that the observed effects of combined administration of CBZ and OLA may be due to the pharmacokinetic interactions, but further studies are necessary to confirm these assumptions.

The cost of inpatient care of schizophrenia in the Polish and Ukrainian academic centers--Poznan and Lviv.

ObjectiveThe authors aimed to analyze and compare treatments of schizophrenia in Poznan and Lviv to present the potential differences between Poland and Ukraine in pharmacotherapy and economic availability of medicines, to emphasize the role of academic centers in the effective treatment of schizophrenia, and to raise the awareness of residents about economics and the cost of inpatient care.MethodsThe analysis was based on 307 hospital records of patients treated in 2010 and 2011 and data from the hospital accounting department. Per the inclusion criteria, 108 adult patients (50 in Poznan and 58 in Lviv) were enrolled in the study. Monetary values were converted into euros (EUR) at the rate published by the National Bank of Poland (NBP) on October 9, 2012.ResultsThe total cost of schizophrenia treatment in Poznan was EUR 160,489.26, x¯