Anna Czubak

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.

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.

Effect of valproic acid and environmental enrichment on behavioral functions in rats

Deficits of cognitive functions are perceived as an important pathogenic factor of many neurological and psychiatric diseases. Such symptoms can be a result of a disease process or appear due to applied medication. Epilepsy is a disease in which cognitive deficits can occur before first seizures, during seizures and remissions. Valproic acid (VAL, CAS 77372-61-3) is a medicine applied in order to control epileptic seizures and mood stabilizing in bipolar disorders and mania. Its activity is related to the effect on neurotransmission of many systems. The present study was conducted to investigate whether enriched environment (EE) conditions affect learning and memory, and influence the antidepressant effect in rats. VAL improves spatial memory upon repeated administration both in the rats housed in standard conditions (SC) (after 21 days of treatment) and those housed in enriched environment (as early as after 14 days of treatment). VAL has an antidepressant effect on the forced swimming test both in the rats housed in standard conditions and those housed in EE. In rats housed in EE, the antidepressant effect occurred much earlier (as early as after 7 days ofVAL administration). It is worth noting that VAL has a low profile of adverse effects (Activity Meter, chimney test). The correlations observed may be translated into clinical effects, leading to new, more effective VAL therapies in depression or memory disorders in patients with underlying epilepsy.

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.

Effect of gabapentin on cognitive processes in rats not exposed and exposed to tobacco smoke during fetal life.

Cognitive deficits, including memory deficiencies, are currently deemed one of key symptoms of psychopathologic mental disorders or epilepsy. The impairment of neurocognitive processes could be due to the administered therapy, in particular combined therapy or therapy using antiepileptics of older type. Gabapentin (GBP) is one of new antiepileptics with normothymic properties. It is known that epileptic patients run a significant risk of developing depression and mood changes. Smoking may also have a negative effect on memory processes and efficacy of administered drugs. Note that smoking in pregnant women also leads to neurobehavioral changes in their children. The objective of our research was to evaluate the effect of GBP on memory functions and antidepressant effect in rats not exposed and exposed to tobacco smoke in fetal life. We were also intent on finding whether GBP has an anticonvulsant effect in contact and without contact with tobacco smoke, and whether it affects motor coordination in animals if administered in the dose of 25 mg/kg. Spatial memory of the animals was assessed in the Morris test and the antidepressant effect in the Porsolt test. The ED50 value was determined in the Swinyard maximum electric shock test, and the effect on motor coordination was assessed in the chimney test. GBP administered in the dose of 25 mg/kg intraperitoneal (i.p.) significantly reduced the immobility time on days 1 and 7 of the test in animals exposed to tobacco smoke, and on days 7 and 14 of the test in rats not exposed to tobacco smoke. Upon single and multiple administration of GBP to animals not exposed to tobacco smoke, the spatial memory improved, whereas in animals exposed to tobacco smoke in fetal life tolerance for procognitive effect was observed on day 21 of the test. It has been found that in rats not exposed to tobacco smoke, ED50 of GBP was 28.73 mg/kg, whereas in animals exposed to tobacco smoke in fetal life, ED50 was 46.2 mg/kg. Upon 14 and 21 days of drug administration, motor coordination was impaired in both GBP receiving animal groups. In conclusion, GBP beside its anticonvulsant efficacy also improves memory processes and has antidepressant effect. We also proved that GBP may reverse cognitive deficits concerning working memory induced by prenatal exposure to tobacco smoke and may have antidepressant effect in rats exposed to tobacco smoke.

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.

Effect of lamotrigine and environmental enrichment on spatial memory and other behavioral functions in rats.

Epileptic patients are at risk of experiencing cognitive deficits as a result of pharmacotherapy as well as etiology of epilepsy. Antiepileptic drugs increase inhibitory neurotransmission and reduce the responsiveness of neurons, and thereby may have a negative impact on memory. The enriched environment intensifies exploration of the new area behavior, which may have a positive impact on spatial memory in rats. Depression is among the most common affective disorders in epileptic patients, and using antidepressant drugs together with antiepileptics brings about the risk of interactions and intensifying side effects, The aim of the study was to assess the effects of lamotrigine (CAS 84057-84-1, LTG) (10 mg/kg i.p.), a new anticonvulsant with antidepresssant and neuroprotective properties, for memory and other behavioral functions in rats in standard and enriched environments (EE). LTG improved spatial memory upon repeated administration of the drug both in the rats housed in standard conditions and those housed in EE. Exposure to an enriched environmentsignificantly improved spatial learning. LTG showed antidepressant effect on the forced swimming test both in the rats housed in standard conditions and those housed in EE. In rats housed in EE the antidepressant effect occurred earlier. LTG had a low profile of adverse effects (activity meter, chimney test).

Interactions of nicotine and drugs used in the treatment of mental illnesses with respect to cognitive functions.

Cognitive disorders in the course of mental illnesses are one of the most important and most difficult therapeutic problems related to those illnesses and they regard attention, memory, learning and sensory modulation. The limited number of nicotinic receptors (subtypes alpha7 and alpha4beta2) seems to cause the incidence and exacerbation of cognitive deficits in such patients. In patients with schizophrenia, the impairment of cognitive processes is also a side-effect of neuroleptics. The characteristics and intensity of the negative effect of antipsychotics on cognitive functions depends on the pharmacological action of those drugs and on the effect on dopamine and serotoninergic receptors in particular. Cognitive function deficits observed in various mental illnesses can be modified with the use of nicotine. A cholinergic neurotransmission system is a common transmission system in the central nervous system. The effect of nicotine on other neurotransmission systems--the dopaminergic and glutaminergic systems--seems to be significant for their efficacious cognitive effects in combination with antipsychotic drugs. Nicotine may also alleviate symptoms of depression, as it amplifies serotoninergic and noradrenergic neuronal activity. When studies on treating cognitive disorders with nicotine are carried out, nicotines interactions with other drugs used in therapy of those disorders must be taken into account as well as the effect of this substance on neurotransmission systems.