Effects of Asenapine and Paliperidone on Depression, Anxiety and Analgesy in Mice: Alterations in Brain Neurotrophic Factors, Neurogenesis, and Blood Enzyme Levels.

Schizophrenia, an important brain neurodevelopmental disorder, is observed in 1% of the global population. New-generation antipsychotics have been developed as alternatives to typical antipsychotics for more effective and safe therapy. Chronic administration of asenapine and paliperidone compared to haloperidol on depression, anxiety and analgesy in the forced swimming test (FST), elevated plus maze (EPM) and hot plate tests were examined in mice. Moreover effects of drugs, on expression levels of brain neurotrophic factors [brain-derived neurotrophic factor (BDNF), cAMP response element binding protein (CREB),nerve growth factor (NGF), synapsin and fibroblast growth factor 2 (FGF2)] in the hippocampus of mice, neurogenesis and neurodegeneration, and blood enzyme levels were also investigated. In FST, haloperidol (0.25 mg/kg) significantly increased immobility time while both asenapine (0.075 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly diminished this parameter. In EPM test, haloperidol significantly increased both % time spent in open arms and % open arm entries. Asenapine (0.075 mg/kg) and paliperidone (0.50 mg/kg) significantly increased % time spent in the open arms. They also increased % open arm entries, but this parameter failed to reach a statistically significant value. In hot plate test, haloperidol (0.125 and 0.25 mg/kg) and paliperidone (0.25 and 0.50 mg/kg) significantly increased the latency to lick the hind paws but asenapine had no effect. Asenapine and paliperidone upregulated more neurotrophic factors in the brain and caused less neurodegeneration compared to haloperidol. Investigated drugs had no effect on liver enzymes and plasma glucose levels. Asenapine and paliperidone may be preferred over classical antipsychotics since they have antidepressant-like effect, upregulate more neurotrophic factors and cause less neurodegeneration in naive mice without having diabetogenic and liver damaging effects. Paliperidone seems to possess superior effects compared to asenapine since it also exerts analgesic-like effect.

Effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on MK-801-induced schizophrenia models.

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), Pht-HrTH (2 mg/kg), MK-801 (0.15 mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1 mg/kg), Lia-AKH (1 mg/kg), Pht-HrTH (1 mg/kg), MK-801 (0.1 mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2 mg/kg), Lia-AKH (2 mg/kg), and Pht-HrTH (2 mg/kg) reversed MK-801 (0.15 mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1 mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1 mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

Effects of Acute Administration of Adipokinetic Hormone on Depression, Anxiety, Pain, Locomotion and Memory in Mice.

The neurosecretory cells in the corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosemic or hyperprolinemic depending on the insect in question. They are the Adipokinetic Hormone/Red Pigment-Concentrating Hormone (AKH/RPCH) family of peptides. The present study investigated the effects of acute administration of Locusta Migratoria (Locmi-AKHII) and Anax Imperator (Anaim-AKH) on depression, anxiety, pain (analgesy), locomotion and memory in mice in forced swimming (FST), elevated plus maze (EPM), hot plate, locomotor activity and passive avoidance tests. Both Locmi-AKH-II (4 mg/kg) and Anaim-AKH (0.25 and 0.50 mg/kg) decreased immobility time (in sec, s) in the FST test. Anaim-AKH (0.5 and 1 mg/kg) increased the percentage of time spent in open arms/total time spent and the percentage of the number of open arm/total arm entries in the EPM test. Anaim-AKH (1 and 2 mg/kg) significantly increased latency (s) (initial time passed) for mice to lick their hind paws or jumping in the hot plate test. Anaim-AKH (4 mg/kg) significantly decreased the total distance (cm) moved, or the speed (cm/s) of movement of the animals in the locomotor activity test. Neither Locmi-AKH-II nor Anaim-AKH altered the retention latency (s) in the passive avoidance test. Both Locmi-AKH-II and Anaim-AKH exerted antidepressant effects, while only Anaim-AKH had anxiolytic and analgesic effects when administered acutely. Anaim-AKH diminished locomotion at higher doses while Locmi-AKH-II had no such effects. Neither Locmi-AKH-II nor Anaim-AKH disturbed learning and memory when acutely administered. Data of our studies suggest clinical potentials of AKH to be used in depression, anxiety and pain without disturbing memory.

Superior effects of quetiapine compared with aripiprazole and iloperidone on MK-801-induced olfactory memory impairment in female mice.

Cognitive dysfunction is commonly observed in schizophrenic patients and the administration of antipsychotic treatments results in different outcomes. Although the typical antipsychotic treatments, such as haloperidol, appear to be unable to improve cognition dysfunction, the atypical antipsychotic drugs (quetiapine, aripiprazole and iloperidone) exert a beneficial effect. The purpose of the current study was to investigate the effects of atypical antipsychotics on olfactory memory in mice, utilizing the social transmission of food preference (STFP) tests to evaluate the effects of drugs on MK-801-induced cognitive dysfunction. Female BALB/c mice were treated with quetiapine (5 and 10 mg/kg), aripiprazole (3 and 6 mg/kg), iloperidone (0.5 and 1 mg/kg) or MK-801 (0.1 mg/kg) alone or concurrently prior to retention sessions of STFP tests. In the STFP tests, quetiapine (10 mg/kg; P<0.05), aripiprazole (3 and 6 mg/kg; P<0.01 and P<0.001, respectively), iloperidone (0.5 and 1 mg/kg; P<0.01 and P<0.001, respectively) and MK-801 (P<0.001) significantly decreased cued/total food eaten (%). Quetiapine (5 mg/kg; P<0.05) significantly increased MK-801-induced decreases in cued/total food eaten (%), while aripiprazole and iloperidone demonstrated no significant effects. The results revealed that all of the drugs disturbed olfactory memory in the naive mice; however, only quetiapine reversed MK-801-induced memory impairment in the STFP test.

Exenatide enhances cognitive performance and upregulates neurotrophic factor gene expression levels in diabetic mice.

Exenatide is a potent and selective agonist for the GLP-1 (glucagon-like peptide-1) receptor. Recent studies are focused on the effects of GLP-1 analogues on hippocampal neurogenesis, cognition, learning and memory functions. The aim of this study was to assess the effects of chronic exenatide treatment (0.1 µg/kg, s.c, twice daily for 2 weeks) on spatial memory functions by using the modified elevated plus maze (mEPM) test and emotional memory functions by using the passive avoidance (PA) test in streptozotocin/nicotinamide (STZ-NA)-induced diabetic mice. As the genes involved in neurite remodelling are among the primary targets of regulation, the effects of diabetes and chronic administration of exenatide on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus of mice were also determined using quantitative real-time polymerase chain reaction (RT-PCR). This study revealed that in the mEPM and PA tests, type-2 diabetes-induced mice exhibited significant impairment of learning and memory which were ameliorated by GLP-1 receptor agonist exenatide. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in diabetic mice, and these alterations were increased by exenatide treatment. Since, exenatide improves cognitive ability in STZ/NA-induced diabetic mice and activates molecular mechanisms of memory storage in response to a learning experience, it may be a candidate for alleviation of mood and cognitive disorder.

Effects of a dragonfly (Anax i.) homeopathic remedy on learning, memory and cell morphology in mice.

BACKGROUND: Homeopathy is a form of alternative medicine in which uses highly diluted preparations that are believed to cause healthy people to exhibit symptoms similar to those exhibited by patients. The aim of this study was to investigate the effects of dragonfly (Anax imperator, Anax i.) on learning and memory in naive mice using the Morris water maze (MWM) test; moreover, the effects of dragonfly on MK-801-induced cognitive dysfunction were evaluated. METHODS: Male balb-c mice were treated with dragonfly (30C and 200C) or MK-801 (0.2 mg/kg) alone or concurrently (n = 10). Dragonfly (D) and MK-801 were administered subchronically for 6 days intraperitoneally 60 min and 30 min, respectively, before the daily performance of the MWM test. RESULTS: This study revealed that in the familiarization session and first session of the MWM test, Anax i. D30 significantly decreased escape latency compared to the control group, although MK-801, D30 and D200 significantly increased escape latency at the end of five acquisition sessions. Anax i. combined with dizocilpine maleate (MK-801) also significantly decreased escape latency in the familiarization session and first session of the MWM test, although this combination increased escape latency compared to the MK-801 alone group at the end of the test. Time spent in escape platform's quadrant in the probe trial significantly decreased while mean distance to platform significantly increased in MK-801, D30 and D200 groups. In the MWM test, Anax i. combined with MK-801 significantly decreased speed of the animals compared to the MK-801 alone group. General cell morphology was disturbed in the MK-801 group while D30 and D200 seemed to improve cell damage in the MK-801 group. CONCLUSIONS: These results suggest that the homeopathic Anax i. can impair learning acquisition and reference memory, and it has beneficial effects on disturbed cell morphology.

Effects of chronic administration of adipokinetic and hypertrehalosemic hormone on animal behavior, BDNF, and CREB expression in the hippocampus and neurogenesis in mice.

Neurosecretory cells in corpus cardiacum of insects synthesize a set of hormones that are called adipokinetic, hypertrehalosaemic or hyperprolinaemic, depending on insect in question. This study investigated effects of chronic administration of Anax imperator adipokinetic hormone (Ani-AKH), Libellula auripennis adipokinetic hormone (Lia-AKH), and Phormia-Terra hypertrehalosaemic hormone (Pht-HrTH) on depression, anxiety, analgesy, locomotion in forced swimming (FST), elevated plus-maze (EPM), hot plate, and locomotor activity tests. Ani-AKH (1 and 2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH (1 and 2 mg/kg) had antidepressant effects in forced swimming test. Lia-AKH (2 mg/kg) and Pht-HrTH (1 and 2 mg/kg) had anxiolytic effects when given chronically in elevated plus-maze test. Ani-AKH (1 and 2 mg/kg) and Pht-HrTH (2 mg/kg) had antinociceptive effects in hot plate test in male balb-c mice. Ani-AKH (2 mg/kg), Lia-AKH (1 and 2 mg/kg), and Pht-HrTH had locomotion-enhancing effects in locomotor activity test in male balb-c mice. Drug treatment significantly increased brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) gene expression levels compared to control levels. Pht-HrTH and Ani-AKH groups had significantly increased numbers of BrdU-labeled cells, while neurodegeneration was lower in the Pht-HrTH group. Our study showed that AKH/RPCH family peptides may be used in treatment of psychiatric illness such as depression and anxiety, in treatment of pain and in diseases related to locomotion system. AKH/RPCH family peptides increase neurotrophic factors in brain and have potential proliferative and neuroprotective effects in hippocampal neurogenesis and neurodegeneration.

7-NI and ODQ Disturbs Memory in the Elevated Plus Maze, Morris Water Maze, and Radial Arm Maze Tests in Mice.

Nitric oxide (NO) is an atypical neurotransmitter that causes changes in cognition. Nitric oxide synthase (NOS) and guanylate cyclase (GC) inhibitors have been shown to exert some effects on cognition in previous studies; however, the findings have been controversial. This study was aimed at understanding the effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on spatial memory in modified elevated plus maze (mEPM), Morris water maze (MWM), and radial arm maze (RAM) tests. Male Balb-c mice were treated via intraperitoneal injections with 7-NI (15 mg/kg), ODQ (3, 10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. ODQ (3 mg/kg) and 7-NI (15 mg/kg) significantly increased the second-day latency in the mEPM test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly increased the escape latency in second, third, and fourth sessions, decreased the time spent in the escape platform's quadrant, and increased the mean distance to the platform in the probe trial of the MWM test. ODQ (3, 10 mg/kg) and 7-NI (15 mg/kg) significantly increased the number of errors, whereas only 7-NI increased the latency in the RAM test. The administration of L-arginine (100 mg/kg) prior to 7-NI inverted the effects of 7-NI, which supports the role of NO on cognition. Our study shows that the NO/cGMP/GS pathway can regulate spatial memory in mice.

Effects of homeopathic Anax imperator on behavioural and pain models in mice.

BACKGOUND: Homeopathy is a medical theory and practice that asserts that disease can be cured by remedies that produce symptoms in a healthy person similar to those suffered by a patient with a malady. METHODS: The aim of this study was to investigate effects of homeopathic Anax imperator (dragonfly) (Anax-i 30c and Anax-i 200c) in the forced swim test (FST), elevated plus-maze (EPM) test, hot plate (HP) test and open field test and examined NPY1 receptor expression, in naive mice. RESULTS: In the FST, treatment with Anax-i 30c or Anax-i 200c significantly diminished immobility time while in EPM test, Anax-i 200c increased the percentage of time spent in open arms as well as the percentage of open arm/total arms. In the HP test, Anax-i 30c or Anax-i 200c decreased the total time mice spent licking their hind paws while in open field test, treatment with Anax-i 200c increased the total distance and speed mice traveled compared to the control group. Three weeks of daily injections with Anax-i 30c or Anax-i 200c caused significant weight loss in mice. Anax-i 30c or Anax-i 200c treatment significantly decreased NPY1 receptor expression, and Anax-i 30c also decreased NPY2 receptor expression. CONCLUSION: These results suggest that the homeopathic Anax-i exerts antidepressant, anxiolytic and analgesic-like effects and causes hyperlocomotion and weight loss.

Zaprinast and rolipram enhances spatial and emotional memory in the elevated plus maze and passive avoidance tests and diminishes exploratory activity in naive mice.

BACKGROUND: Phosphodiesterase (PDE) inhibitors in the central nervous system have been shown to stimulate neuronal functions and increase neurogenesis in Alzheimer disease (AD) patients. MATERIAL/METHODS: The aim of this study was to investigate the effects of zaprinast, a PDE5 inhibitor, and rolipram, a PDE4 inhibitor, on learning and memory in elevated plus maze (EPM) and passive avoidance (PA) tests in naive mice. Male Balb-c mice received short-term treatment with zaprinast (3 and 10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) before the acquisition trial of the EPM and PA tests. The exploratory activity of the animals was also investigated in the Hughes box test. RESULTS: Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased second-day latency compared to the control group in the EPM test, while only rolipram (0.1 mg/kg) significantly increased second-day latency in the PA test. Both zaprinast (10 mg/kg) and rolipram (0.1 mg/kg) significantly decreased the number of entries to new areas and time spent in new areas in the Hughes box test. CONCLUSIONS: Our study revealed that both zaprinast and rolipram enhanced spatial memory in EPM, while rolipram seemed to have more emotional memory-enhancing effects in the PA test compared to zaprinast. Both zaprinast and rolipram diminished exploratory activity in the Hughes box test, which can be attributed to the drugs' anxiogenic effects.

Exenatide treatment exerts anxiolytic- and antidepressant-like effects and reverses neuropathy in a mouse model of type-2 diabetes.

BACKGROUND: Comorbid neurobehavioral disturbances and type-2 diabetes mellitus (T2DM) warrant immediate research attention. Exenatide, which is a potent and selective agonist for the glucagon-like peptide-1 (GLP-1), is used in the treatment of T2DM. Exenatide displays a multitude of effects in the central nervous system. The aim of this study was to investigate the anxiolytic- and antidepressant-like effects and analgesic effects of exenatide in a type-2 diabetic mouse model. MATERIAL/METHODS: Modified elevated plus-maze test for anxiolytic-like, forced swimming test for depression-like behavior and hotplate test for neuropathy were used as behavioral tasks. Behavioral parameters were investigated in a streptozocin--(100 mg/kg, i.p.) and nicotinamide--(240 mg/kg, i.p.) induced type-2 diabetic mouse model. Exenatide (0.1 µg/kg, s.c., twice daily) was administered for 2 weeks. Vehicle (control), diabetic, and exenatide-treated diabetic mice were tested. RESULTS: Our results confirm that exenatide exerts anxiolytic- and antidepressant-like effects and might be effective in diabetic neuropathy in a diabetic mouse model. CONCLUSIONS: Exenatide may be a good candidate as a treatment option for depression, anxiety, and neuropathy in patients with type-2 diabetes.

Effects of zaprinast and rolipram on olfactory and visual memory in the social transmission of food preference and novel object recognition tests in mice.

The role of phosphodiesterase (PDE) inhibitors in central nervous system has been investigated and shown to stimulate neuronal functions and increase neurogenesis in Alzheimer patients. The aim of this study is to investigate effect of PDE5 inhibitor zaprinast and PDE4 inhibitor rolipram on visual memory in novel object recognition (NOR) test, on olfactory memory in social transmission of food preference (STFP) test, and also on locomotion and anxiety in open field test in naive mice. Male Balb-c mice were treated intraperitoneally (i.p.) with zaprinast (3 and 10 mg/kg), rolipram (0.05 and 0.1 mg/kg), or physiological saline. Zaprinast (10 mg/kg) significantly increased cued/non-cued food eaten compared to control group, while rolipram had a partial effect on retention trial of STFP test. Zaprinast (10 mg/kg) and rolipram (0.05 and 0.1 mg/kg) significantly increased ratio index (RI) compared to control group in retention trial of NOR test. There was no significant effect of zaprinast and rolipram on total distance moved, speed, and center zone duration in open field test. Results of this study revealed that both zaprinast and rolipram enhanced visual memory in NOR test, however zaprinast exerted a significant memory-enhancing effect compared to rolipram in STFP test in mice.

Effects of 7-NI and ODQ on memory in the passive avoidance, novel object recognition, and social transmission of food preference tests in mice.

BACKGROUND: Nitric oxide (NO) is an intercellular messenger that plays a critical role in learning and memory processes. Effects of nitric oxide synthase (NOS) inhibitors and guanylate cyclase (GC) inhibitors on cognitive function remain controversial. MATERIAL AND METHODS: The aim of this study was to investigate effects of an NOS inhibitor, 7-nitroindazole (7-NI), and a GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), on different aspects of memory in passive avoidance (PA), novel object recognition (NOR), and social transmission of food preference (STFP) tests. Male Balb-c mice were treated intraperitoneally with 7-NI (15 mg/kg), ODQ (3,10 mg/kg), L-arginine (100 mg/kg) + 7-NI (15 mg/kg), or physiological saline. RESULTS: ODQ (10 mg/kg) and 7-NI (15 mg/kg) significantly decreased second-day latency in PA test. 7-NI (15 mg/kg) and ODQ (10 mg/kg) significantly decreased the ratio index in the NOR test. 7-NI and ODQ (10 mg/kg) decreased cued/non-cued food eaten in STFP test. Amount of time spent in center zone significantly increased in ODQ (10 mg/kg) and 7-NI (15 mg/kg) groups in open field test, but there was no effect on total distance moved and speed of animals. ODQ (10 mg/kg) significantly increased number of entries into new compartments in exploratory activity apparatus, while 7-NI had no effect. Administration of L-arginine (100 mg/kg) before 7-NI reversed 7-NI-induced effects, supporting the role of NO in cognition. CONCLUSIONS: Our results confirm that inhibition of NO/cGMP/GS pathway might disturb emotional, visual, and olfactory memory in mice. Also, 7-NI and ODQ had anxiolytic effects in open field test, and ODQ also enhanced exploratory activity.

The Antidepressant Agomelatine Improves Memory Deterioration and Upregulates CREB and BDNF Gene Expression Levels in Unpredictable Chronic Mild Stress (UCMS)-Exposed Mice.

Agomelatine, a novel antidepressant with established clinical efficacy, acts as an agonist of melatonergic MT1 and MT2 receptors and as an antagonist of 5-HT2C receptors. The present study was undertaken to investigate whether chronic treatment with agomelatine would block unpredictable chronic mild stress (UCMS)-induced cognitive deterioration in mice in passive avoidance (PA), modified elevated plus maze (mEPM), novel object recognition (NOR), and Morris water maze (MWM) tests. Moreover, the effects of stress and agomelatine on brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) messenger ribonucleic acid (mRNA) levels in the hippocampus was also determined using quantitative real-time polymerase chain reaction (RT-PCR). Male inbred BALB/c mice were treated with agomelatine (10 mg/kg, i.p.), melatonin (10 mg/kg), or vehicle daily for five weeks. The results of this study revealed that UCMS-exposed animals exhibited memory deterioration in the PA, mEPM, NOR, and MWM tests. The chronic administration of melatonin had a positive effect in the PA and +mEPM tests, whereas agomelatine had a partial effect. Both agomelatine and melatonin blocked stress-induced impairment in visual memory in the NOR test and reversed spatial learning and memory impairment in the stressed group in the MWM test. Quantitative RT-PCR revealed that CREB and BDNF gene expression levels were downregulated in UCMS-exposed mice, and these alterations were reversed by chronic agomelatine or melatonin treatment. Thus, agomelatine plays an important role in blocking stress-induced hippocampal memory deterioration and activates molecular mechanisms of memory storage in response to a learning experience.

Effects of fluoxetine, tianeptine and olanzapine on unpredictable chronic mild stress-induced depression-like behavior in mice.

AIMS: Tianeptine is an atypical antidepressant drug that has a different mechanism of action than other antidepressants. Olanzapine is an atypical antipsychotic drug used for the treatment of schizophrenia. The present study was undertaken to investigate effects of chronic administration of tianeptine or olanzapine on unpredictable chronic mild stress (UCMS)-induced depression-like behavior in mice compared to a widely used SSRI antidepressant, fluoxetine. MAIN METHODS: Male inbred BALB/c mice were subjected to different kinds of stressors several times a day for 7weeks and were treated intraperitoneally with tianeptine (5mg/kg), olanzapine (2.5mg/kg), fluoxetine (15mg/kg) or vehicle for 5weeks (n=7-8 per group). KEY FINDINGS: All the drugs tested prevented stress-induced deficit in coat state during UCMS procedure, in grooming behavior in the splash test, decreased the attack frequency in the resident intruder test and decreased the immobility time in the tail suspension test. In the open field test olanzapine had anxiolytic-like effects in both stressed and non-stressed mice. Tianeptine, olanzapine and fluoxetine decreased the enhanced levels of plasma ACTH and IL-6. Chronic treatment with tianeptine resulted in a significant increase in both total number and density of BrdU-labeled cells in stressed animals, while fluoxetine and olanzapine had a partial effect. SIGNIFICANCE: The results of this study support the hypothesis that tianeptine can be as effective as fluoxetine for the treatment of depression in spite of the differences in the mechanism of action of these drugs. Moreover, olanzapine could be used effectively in psychotic patients with depression.

Lamotrigine, a mood stabilizer, may have beneficial effects on memory acquisition and retrieval in mice.

AIMS: The aim of this study was to investigate the effects of a mood stabilizer lamotrigine (LMG) on learning and memory processes using Morris water maze (MWM), modified elevated plus maze (mEPM) and passive avoidance (PA) tests. MAIN METHODS: Balb-c mice were used. LMG were injected (20; 40mg/kg, intraperitoneal, i.p.) into mice before the probe trial of MWM test and before the acquisition session of mEPM and PA tests. KEY FINDINGS: On the probe trial of MWM test, LMG (40mg/kg) significantly prolonged the "time spent in target quadrant" compared to control and LMG (20mg/kg). LMG (40mg/kg) decreased the "distance to platform" compared to control. Both doses of LMG did not change the "swim speed" of animals. In the mEPM test, in comparison of transfer latency on the first day and transfer latency on the second day for each group, transfer latency on the second day was significantly decreased in the control and LMG-treated groups. Second day transfer latencies compared in-between the group transfer latency of on second days significantly decreased by LMG (20mg/kg and 40mg/kg) treatment compared to control. In the PA test, retention latency significantly prolonged by LMG (40mg/kg) treatment compared to control and LMG (20mg/kg). SIGNIFICANCE: Our results may indicate that, LMG may have some ameliorating effects on spatial memory retrieval on the MWM test. LMG positively affected the acquisition of memory in the mEPM and in the PA test in naive mice.

Lamotrigine effects sensorimotor gating in WAG/Rij rats.

INTRODUCTION: Prepulse inhibition (PPI) is a measurable form of sensorimotor gating. Disruption of PPI reflects the impairment in the neural filtering process of mental functions that are related to the transformation of an external stimuli to a response. Impairment of PPI is reported in neuropsychiatric illnesses such as schizophrenia, Huntington's disease, Parkinson's diseases, Tourette syndrome, obsessive compulsive disorder, and temporal lobe epilepsy with psychosis. Absence epilepsy is the most common type of primary generalized epilepsy. Lamotrigine is an antiepileptic drug that is preferred in absence epilepsy and acts by stabilizing the voltage-gated sodium channels. AIM: In this study, we have compared WAG-Rij rats (genetically absence epileptic rats) with Wistar rats, in order to clarify if there is a deficient sensorimotor gating in absence epilepsy, and have examined the effects of lamotrigine (15, 30 mg/kg, i.p.) on this phenomenon. MATERIALS AND METHODS: Depletion in PPI percent value is accepted as a disruption in sensory-motor filtration function. The difference between the Wistar and WAG/Rij rats has been evaluated with the student t test and the effects of lamotrigine on the PPI percent have been evaluated by the analysis of variance (ANOVA) post-hoc Dunnett's test. RESULTS: The PPI percent was low in the WAG/Rij rats compared to the controls (P<0.0001, t:9,612). Although the PPI percent value of the control rats was not influenced by lamotrigine, the PPI percent value of the WAG/Rij rats was raised by lamotrigine treatment (P<0.0001, F:861,24). CONCLUSIONS: As a result of our study, PPI was disrupted in the WAG/Rij rats and this disruption could be reversed by an antiepileptic lamotrigine.

Positive impact of levetiracetam on emotional learning and memory in naive mice.

AIMS: The effect of an antiepileptic drug on cognitive function is of primary importance with respect to the patient's quality of life. Levetiracetam (LEV) is a novel antiepileptic drug used to treat epilepsy, but its effects on spatial and emotional learning and memory are not yet well understood. The goal of our study was to establish the effects of LEV (17 and 54 mg/kg, intraperitoneally (IP)) on spatial memory retrieval in the Morris water maze test and on acquisition and memory formation in the passive avoidance (PA) test in naive mice. MAIN METHODS: The subjects were adult male BALB/c mice. Spatial learning and memory was established with the Morris water maze (MWM) test. The 'time spent in escape platforms quadrant' and the 'distance to platform' analyses were measured using a video tracking system to determine spatial memory function. Emotional learning and memory were determined with a one-trial, step-through passive avoidance test. KEY FINDINGS: In the MWM test, LEV (17 and 54 mg/kg) neither affected the time spent in the target quadrant nor altered the distance to platform. Moreover, LEV had no effect on swim speed. In the PA task, LEV (17 and 54 mg/kg) significantly prolonged retention latency. SIGNIFICANCE: Our results indicate that LEV did not alter spatial memory retrieval in the MWM test, but it did show some ameliorating effects on acquisition and memory formation in the PA test in naive mice.

Effects of citalopram on cognitive performance in passive avoidance, elevated plus-maze and three-panel runway tasks in naïve rats.

Recent studies have shown that learning and memory capacity is disturbed in depressive patients, and it is important to reveal the effects of antidepressant drugs on cognitive function in depressive patients with memory problems. Citalopram, a selective serotonin reuptake inhibitor (SSRI), is one of the most widely used drugs for the treatment of disorders related to serotonergic dysfunction like depression and anxiety. Contradictory findings exist regarding the effects of SSRIs on memory. The aim of this study is to investigate whether citalopram affects memory in various models of learning and memory tasks in rats. Citalopram (at 20 and 50 mg/kg) significantly shortened the retention latency in the passive avoidance test and prolonged the transfer latency on the second day at 10 and 50 mg/kg doses in the elevated plus-maze test. Citalopram also significantly increased the number of errors (at the 10 mg/kg dose) and prolonged the latency values compared to the control group in both reference and working memory trials in the three-panel runway test. Citalopram also impaired reference memory trials of animals at the 20 mg/kg dose. In conclusion, citalopram impaired cognitive performance in passive avoidance, elevated plus-maze and three-panel runway tasks in naive rats. These effects might be related to serotonergic and nitrergic mechanisms, which need to be investigated in further studies.

Effects of olanzapine and clozapine on memory acquisition, consolidation and retrieval in mice using the elevated plus maze test.

Clozapine and olanzapine are antipsychotic drugs commonly used to treat schizophrenia and psychosis; however, few studies have investigated their effects on cognitive function using animal models. Thus, the effects of olanzapine and clozapine on memory acquisition, consolidation and retrieval were investigated in naive mice using a modified elevated plus maze (mEPM) task. Olanzapine (0.15 and 0.30 mg/kg) and clozapine (0.5 and 1 mg/kg) were injected intraperitoneally (i.p.) into male Balb-c mice before training, immediately after training or before the second day of the trial. Our results showed that both olanzapine and clozapine disrupted the acquisition of spatial memory. In addition, clozapine impaired the consolidation of spatial memory, while olanzapine had no effect. Furthermore, olanzapine and clozapine significantly disrupted memory retrieval in naive mice. Thus, these results at least suggest that olanzapine can be a superior treatment for schizophrenia compared to clozapine.