Piotr Ratajczak

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.

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).

Coadministration of tramadol with aripiprazole and venlafaxine—The effect on spatial memory functions in male rats

BACKGROUND The impairment of memory functions is very common in patients with chronic pain, particularly in patients with existing cognitive disorders. Results of some studies confirmed that tramadol (TRM), a frequently prescribed analgesic drug, improves memory functions in humans. However, there are no studies on the effect of co-administration of TRM with antidepressants or antipsychotics on memory; therefore, the aim of this study was to evaluate the effect of concomitant use of TRM with a second generation antipsychotic-aripiprazole (ARI) and an antidepressant-venlafaxine (VEN) on memory using an animal model. METHODS The effect of TRM (5mg/kg)+ARI (1.5mg/kg) and TRM (5mg/kg)+VEN (20mg/kg) on memory in Wistar rats was examined using the Morris water maze test after single and chronic administration (7 and 14 days). RESULTS It was observed that a single and chronic administration of TRM, VEN or ARI alone, but not a combination of TRM+VEN or TRM+ARI (except for 14 days of treatment) can improve memory in rats compared to the control group. After 14 days of administration, both combinations achieved improvement similar to each drug individually and improved spatial memory in rats compared to the control animals. CONCLUSION It can be assumed that chronic treatment with combinations of TRM+VEN or TRM+ARI is unlikely to cause memory impairment and interfere with either any antidepressant effect of VEN or any antipsychotic effect of ARI in patients suffering from chronic pain using TRM.

Evaluation of antidepressant and memory-improving efficacy of aripiprazole and fluoxetine in alcohol-preferring rats

Introduction and aims Dependence on ethanol increases the risk of depression in patients and leads to a damage and deficiencies of brain function, which manifest in cognitive functions impairment. Aripiprazole (ARI) is an atypical antipsychotic drug, which has also been shown to have a beneficial effect on cognitive function. Results of many studies show that, for ARIs antidepressant effect to manifest itself, it is necessary to use a combined therapy with a drug from the group of selective serotonin reuptake inhibitors (SSRIs). The aim of this paper was to assess the antidepressant and impact of ARI on spatial memory in alcohol-preferring rats (EtNPRs). Design and methods In our study, we used Porsolts forced swimming test (antidepressant effect) and Morris water maze test. The tests have been conducted upon administration of ARI (6 mg/kg i.p.), fluoxetine (FLX; 5 mg/kg p.o.) and combined administration of both drugs in alcohol-dependent rats. Results The results of behavioural tests carried out have shown a lack of antidepressant and procognitive effects of either ARI or FLX in EtPRs after acute and chronic treatment. Combined administration of both drugs would lead to spatial memory deterioration in the study animals. Discussion and conclusions Our results suggest that ARI applied in the experiment had no antidepressant effect and failed to improve spatial memory in study rats. Potential antidepressant and procognitive properties of this drug resulting from its mechanism of action encourage attempts (design) of further research aimed at developing a dose, which will show such effects in alcohol-preferring animals.

The effect of ethyl alcohol on the function of spatial memory in rats.

Alcoholism is a mental disease in the course of which depression, anxiety, and cognitive function deficits may appear, and these symptoms can be aggravated by comorbid schizophrenia.The aim of this study was to find whether spatial memory (Morris Water Maze) function impairment is found in prenatally stressed rats (PSG) (prenatal stress paradigm - animal model of schizophrenia) and whether aripiprazole ARI and olanzapine OLA modify these functions. It was also important to study the effect of ethyl alcohol administered to rats.Behavioural tests showed that ARI and OLA improved spatial memory in the non-stressed control group (NSCG) and in the PSG. Moreover, spatial memory in the non-stressed alcohol group (NSAG) improved significantly compared to the NSCG, while in the prenatally stressed alcohol group (PSAG) spatial memory improved both in comparison to the NSCG and PSG. No statistically significant differences were found by comparing groups which received ethyl alcohol (NSAG, PSAG).

The influence of aripiprazole and olanzapine on neurotransmitters level in frontal cortex of prenatally stressed rats

OBJECTIVES The study aims to verify whether alterations in the level of neurotransmitters have occurred in prenatally stressed rats (animal model of schizophrenia), and whether aripiprazole (ARI) and olanzapine (OLA) modify this level. METHODS The effects of ARI (1.5mg/kg) and OLA (0.5mg/kg) were studied by means of microdialysis in freely moving rats (observation time 120min). The level of neurotransmitters (DA, 5-HT, NA) and their metabolites (DOPAC, HVA, 5-HIAA) was analyzed by HPLC with coulochemical detection. RESULTS Obtained results indicate that after a single administration of ARI and OLA in the prenatally stressed rats the increase of DA, DOPAC, and 5-HT was observed. In turn ARI administration increase the level of HVA and 5-HIAA and also decrease the level of NA. After OLA administration the level of NA and HVA increased and no significant change in 5-HIAA was observed. CONCLUSION Alterations observed as a result of ARI and OLA administration may be pivotal in identifying animal models of mental disorders and in the analysis of neuroleptics effectiveness.

Evaluation of the antidepressant, anxiolytic and memory-improving efficacy of aripiprazole and fluoxetine in ethanol-treated rats.

Abstract Some study results indicate a positive effect of aripiprazole (ARI) on impaired cognitive functions caused by brain damage resulting from chronic EtOH abuse. However, other research shows that to manifest itself, an ARI antidepressant effect requires a combined therapy with another selective serotonin reuptake inhibitor antidepressant, namely, fluoxetine (FLX). The aim of this article was to assess antidepressant and anxiolytic effects of ARI as well as its effect on spatial memory in ethanol-treated (alcoholized) rats. On the basis of alcohol consumption pattern, groups of (1) ethanol-preferring rats, with mean ethanol intake above 50%, and (2) ethanol-nonpreferring rats (EtNPRs), with mean ethanol intake below 50% of total daily fluid intake, were formed. The group of EtNPRs was used for this study, subdivided further into three groups administered ARI, FLX and a combination of both, respectively. Behavioral tests such as Porsolt’s forced swimming test, the Morris water maze test and the two-compartment exploratory test were employed. Behavioral test results demonstrated (1) no antidepressant effect of ARI in EtNPRs in subchronic treatment and (2) no procognitive effect of ARI and FLX in EtNPRs in combined single administration. Combined administration of both drugs led to an anxiogenic effect and spatial memory deterioration in study animals. ARI had no antidepressant effect and failed to improve spatial memory in rats. However, potential antidepressant, anxiolytic and procognitive properties of the drug resulting from its mechanism of action encourage further research aimed at developing a dose of both ARI and FLX that will prove such effects in alcoholized EtNPRs.

Neuroleptics and enrichment environment treatment in memory disorders and other central nervous system function observed in prenatally stressed rats.

It is believed that the most effective method of treatment in schizophrenia is pharmacotherapy, in particular, the use of atypical neuroleptics like aripiprazole (ARI) and olanzapine (OLA). Moreover, studies of many authors have shown that enriched living conditions and tobacco smoke exposure can also affect the cognitive functions that are disturbed in the course of schizophrenia. The aim of the study was to find whether tobacco smoke and enrichment living conditions have the influence on cognitive functions in the newborn offspring of prenatally stressed rats and whether drugs such as ARI (1.5 mg/kg intraperitoneally (i.p.)) and OLA (0.5 mg/kg ip) in single and chronic treatment modify those functions (Morris water maze). The study (in the same conditions) also analyses immobility time (Porsolt test) and motor activity of animals that received ARI and OLA. It has been shown that ARI and OLA as well as enriched environment reduce cognitive function disorders and modify cognitive functions in rats exposed to tobacco smoke. In turn, current research has shown that nicotine has increased cognitive function disorders compared to the previous study (animals without tobacco smoke exposure).