olanzapine and Memory-Disorders

This meta-analytic review examines the efficacy of antipsychotic medications in ameliorating schizophrenia-related long-term memory (LTM) impairments. Twenty-three studies were reviewed that compared schizophrenia spectrum patients treated (a) with atypical versus typical antipsychotic medications, or (b) with various atypical treatments. In 17 atypical versus typical trials aggregating 939 participants, superior overall (verbal and nonverbal) LTM was detected in patients assigned to atypical trials. However, this difference was small (effect size estimate (ES) 0.17; 95% Confidence Interval (CI) 0.04 to 0.31) and specific to certain atypical treatments. Relative to typical antipsychotic trials, LTM superiority was marginally significant for risperidone trials (ES 0.20; 95% CI -0.03 to 0.44) and significant for olanzapine trials (ES 0.29; 95% CI 0.08 to 0.49). In contrast, clozapine trials did not produce a LTM advantage over typical trials (ES -0.06; 95% CI -0.35 to 0.23). Due to the lack of available studies, the effect of quetiapine was indeterminate. Direct comparison between atypical trials revealed a similar effect pattern. A marginally significant superiority in overall LTM was detected for risperidone and olanzapine compared to clozapine (ES 0.28; 95% CI -0.04 to 0.59), which reached significance for verbal LTM (ES 0.36; 95% CI 0.04 to 0.67). Finally, the beneficial impact of antipsychotic medications emerged as a function of differences in the anticholinergic properties of the treatment arms being compared.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Humans; Memory Disorders; Olanzapine; Retention, Psychology; Risperidone; Schizophrenia

Olanzapine is an atypical antipsychotic for the treatment of schizophrenia, in which memory impairment is a core deficit. The methods of positive and negative syndrome scale (PANSS), Wechsler memory scale-4th edition (WMS-IV) and event-related potential (ERP) were used to study the effects of olanzapine on the cognitive function in the first-episode schizophrenic patients. We performed multicentre, randomized, double-blind, placebo-controlled, parallel-group clinical trial to study the cognitive functioning in Han Chinese first-episode schizophrenic patients in a 12-week treatment regime with olanzapine (129 cases) or placebo (132 cases). The results showed that (1) the patients with first-episode schizophrenia showed significant deficits in the long-term memory, short-term memory, immediate memory and memory quotient by WMS-IV assessment, and decreases the total scores, positive symptoms, negative symptoms and general psychopathology by PANSS assessment; (2) olanzapine could significantly improve the PANSS scores including total scores, positive symptoms, negative symptoms and general psychopathology in the first-episode schizophrenic patients; (3) olanzapine could significantly improve the short-term memory, immediate memory and memory quotient in the first-episode schizophrenic patients; and (3) although the latencies of P(2), N(2) and P(3) were significantly prolonged, P(2) and P(3) amplitudes were decreased and the latencies of N(1) did not change, olanzapine did not influence any P(300) items in the first-episode schizophrenic patients. The data suggested that that olanzapine could improve cognitive process, such as memorizing and extraction of the information although there were many changes of cognitive functions in Han Chinese first-episode schizophrenic patients.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; China; Double-Blind Method; Evoked Potentials; Female; Humans; Male; Memory Disorders; Memory, Short-Term; Middle Aged; Neuropsychological Tests; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Young Adult

Earlier studies have shown widespread alterations of functional connectivity of various brain networks in schizophrenia, including the default mode network (DMN). The DMN has also an important role in the performance of cognitive tasks. Furthermore, treatment with second-generation antipsychotic drugs may ameliorate to some degree working memory (WM) deficits and related brain activity. The aim of this study was to evaluate the effects of treatment with olanzapine monotherapy on functional connectivity among brain regions of the DMN during WM. Seventeen patients underwent an 8-week prospective study and completed two functional magnetic resonance imaging (fMRI) scans at 4 and 8 weeks of treatment during the performance of the N-back WM task. To control for potential repetition effects, 19 healthy controls also underwent two fMRI scans at a similar time interval. We used spatial group-independent component analysis (ICA) to analyze fMRI data. Relative to controls, patients with schizophrenia had reduced connectivity strength within the DMN in posterior cingulate, whereas it was greater in precuneus and inferior parietal lobule. Treatment with olanzapine was associated with increases in DMN connectivity with ventromedial prefrontal cortex, but not in posterior regions of DMN. These results suggest that treatment with olanzapine is associated with the modulation of DMN connectivity in schizophrenia. In addition, our findings suggest critical functional differences in the regions of DMN.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Brain Mapping; Case-Control Studies; Chi-Square Distribution; Female; Follow-Up Studies; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Memory Disorders; Memory, Short-Term; Nerve Net; Neuropsychological Tests; Olanzapine; Oxygen; Principal Component Analysis; Prospective Studies; Schizophrenia; Time Factors; Young Adult

Abnormality of P300 waveforms of event-related potentials (ERPs) has been suggested to represent an aspect of the pathophysiology of schizophrenia. Previous work points to the contribution of altered neural function in discrete brain regions in the left hemisphere to psychotic symptoms and cognitive deficits of schizophrenia. In this study, we sought to determine: 1) if patients with schizophrenia elicit a decreased P300 current source density in brain areas, such as the superior temporal gyrus (STG); 2) if decreased P300 generator density in the left STG is recovered by treatment with the most widely-used antipsychotic drug olanzapine; and 3) if the recovery of P300 source density is associated with improvements of cognitive and functional status. P300 in response to an auditory oddball task, as well as verbal learning memory, psychopathology, and quality of life were evaluated in 16 right-handed patients with schizophrenia before and after treatment with olanzapine for 6 months. ERP data were also obtained from 16 right-handed age and gender-matched normal volunteers. Low resolution electromagnetic tomography (LORETA) analysis was used to obtain current density images of P300. Patients with schizophrenia showed significantly smaller LORETA values in several brain regions in the left side, particularly STG, middle frontal gyrus, and precentral gyrus, compared with control subjects. Six-month treatment with olanzapine significantly increased P300 source density only in the left STG. Positive symptoms, negative symptoms, verbal learning memory, and quality of life were also improved during treatment. Significant correlations were found between the increase in LORETA values of left STG vs. improvements of negative symptoms, as measured by Scale for the Assessment of the Negative Symptoms, and verbal learning memory, as measured by the Japanese Verbal Learning Test. Improvement of quality of life, as evaluated by the Quality of Life Scale, were significantly associated with an increase in LORETA values of middle frontal gyrus, and tended to correlate with that of precentral gyrus. The results of this study suggest that changes in cortical activity, as measured by ERPs, are responsible for the ability of some antipsychotic drugs to improve cognition and functional outcome in patients with schizophrenia.

Topics: Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Brain Mapping; Electroencephalography; Event-Related Potentials, P300; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Memory Disorders; Middle Aged; Neuropsychological Tests; Olanzapine; Regression Analysis; Schizophrenia; Treatment Outcome; Verbal Learning

Memory deficits and sleep disturbances are common clinical features of schizophrenia. Sleep is supposed to promote memory consolidation and the antipsychotic olanzapine is suggested to improve both sleep and memory functions. Therefore we performed a study to analyse the acute effects of olanzapine on distinct sleep parameters and sleep-related memory consolidation in parallel.. We studied 26 patients with schizophrenia on stable antipsychotic medication with amisulpride (age range 19-44 years). Immediately before polysomnography and the morning after we performed neuropsychological tasks. Before the third night in the sleep laboratory, patients received either olanzapine or a placebo.. We found a significant positive association for slow wave sleep and declarative memory performance in schizophrenia at baseline. Additionally, Stage 2 sleep spindle density was positively related to overnight memory consolidation. Olanzapine caused a significant increase in the amount of slow wave sleep in accordance with recent studies, but led also to a significant decrease in sleep spindle density, which had not been described before. Memory performance the next morning was not different between the two groups.. Since not only slow wave sleep but also sleep spindles are supposed to promote sleep-related memory consolidation, we suggest that a putative positive effect on memory performance by slow wave sleep augmentation is neutralised by the decrease in sleep spindles due to olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Olanzapine; Polysomnography; Psychiatric Status Rating Scales; Schizophrenia; Sleep Stages; Sleep Wake Disorders; Surveys and Questionnaires

The study investigated whether four specified drugs would show similar patterns on tests considered to measure sedation. In addition, their drug-effect patterns on sedation and memory performance were compared to determine whether the sedative effects could be differentiated from the memory effects. Two double-blind, placebo-controlled, crossover studies, each with 16 healthy volunteers, were performed, one testing lorazepam (2.5 mg) and mirtazapine (15 mg) and the other olanzapine (10 mg) and haloperidol (2.5 mg). Subjective sedation was assessed by means of visual analogue scales (VAS) and objective sedation using a simple-reaction-time (SRT) task and a choice-reaction-time (CRT) task, code substitution (symbol digit substitution test (SDST)) and the peak velocity of saccadic eye movements (SEM). A verbal memory test (VMT) was administered to evaluate memory capacity. Apart from haloperidol, all drugs proved to impair performance on all five sedation indices. Contrary to the VAS, the objective measures yielded different response profiles. Two types of drug-effect patterns emerged: one for greater impairments in response speed (SRT, SEM) and one for greater impairments in information processing (CRT, SDST). Lorazepam and olanzapine impeded memory performance, whereas mirtazapine did not. With the use of standardized scores it proved possible to differentiate between the size of the effects of the drugs on the sedation and memory tests. To accurately assess the level and nature of sedation and to differentiate sedation from memory impairments different types of sedation measures are required. Besides studying the subjective effects, it is recommended to also test psychomotor responses and information processing speed.

Topics: Adult; Affect; Antipsychotic Agents; Arousal; Benzodiazepines; Choice Behavior; Cross-Over Studies; Double-Blind Method; Female; Haloperidol; Histamine H1 Antagonists; Humans; Hypnotics and Sedatives; Lorazepam; Male; Memory; Memory Disorders; Mianserin; Mirtazapine; Olanzapine; Psychological Tests; Psychomotor Performance; Reaction Time; Reference Values; Saccades; Surveys and Questionnaires; Verbal Learning

Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val(108/158)Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug.. Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks.. There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale.. These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Catechol O-Methyltransferase; Dopamine; Female; Genotype; Humans; Longitudinal Studies; Magnetic Resonance Imaging; Male; Memory Disorders; Methionine; Neuropsychological Tests; Olanzapine; Polymorphism, Genetic; Prefrontal Cortex; Prospective Studies; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Valine

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

Topics: Animals; Antipsychotic Agents; Autism Spectrum Disorder; Autistic Disorder; Behavior, Animal; Disease Models, Animal; Female; Humans; Male; Memory Disorders; Neurons; Olanzapine; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Social Behavior; Valproic Acid

Effects of sertraline, haloperidol or olanzapine administration on ketamine-induced behaviours in mice were examined. The aim was to ascertain the degree of reversal of such behaviours by sertraline, and compare its effectiveness to haloperidol and olanzapine. Ten-week old mice (N = 120) were equally divided into main groups; 1 (open-field, radial-arm maze and elevated plus maze {EPM} tests), and 2 (social interaction test). Mice in each main group were assigned into six groups of ten (n = 10) each. Group 1 received intraperitoneal (i.p) injection of vehicle, while groups 2-6 received i.p ketamine at 15 mg/kg daily for 10 days. From day 11 to 24, mice in group 1 (vehicle) were given distilled water (i.p at 2 ml/kg and oral at 10 ml/kg), group 2 (ketamine control) received daily i.p ketamine and oral distilled water; while animals in groups 3-6 received daily i.p. ketamine and oral haloperidol (4 mg/kg), olanzapine (2 mg/kg), or one of two doses of sertraline (SERT) (2.5 or 5 mg/kg), respectively. Treatments were administered daily, and behaviours assessed on days 11 and 24. Results showed that repeated ketamine administration caused hyperlocomotion, increased self-grooming, memory loss and social withdrawal. Administration of sertraline (both doses), haloperidol, and olanzapine reversed ketamine-induced behavioural changes. However, in the EPM, sertraline and olanzapine were anxiolytic, while haloperidol was anxiogenic. Sertraline's effect on behaviours tested was comparable to olanzapine and better than haloperidol. In conclusion, this study shows that sertraline's ability to counteract ketamine-induced behavioural changes in mice is comparable to known antipsychotics.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Anxiety; Behavior, Animal; Benzodiazepines; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Exploratory Behavior; Grooming; Haloperidol; Interpersonal Relations; Ketamine; Male; Memory Disorders; Memory, Short-Term; Mice; Motor Activity; Olanzapine; Sertraline

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).

Topics: Animals; Antipsychotic Agents; Aripiprazole; Behavior, Animal; Benzodiazepines; Female; Gestational Age; Male; Maze Learning; Memory Disorders; Motor Activity; Olanzapine; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Wistar; Smoking; Social Environment

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).. 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.. 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.. 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).

Topics: Animals; Antidepressive Agents; Aripiprazole; Benzodiazepines; Brain-Derived Neurotrophic Factor; Depression; Environment; Female; Hippocampus; Male; Maze Learning; Memory Disorders; Olanzapine; Piperazines; Pregnancy; Quinolones; Rats; Rats, Wistar; Spatial Memory

Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28-49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABA(A) receptors with open Cl(-) channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and neurobiological responses to other therapeutic- or illicit psychotropic drugs.

Topics: Age Factors; Animals; Antipsychotic Agents; Benzodiazepines; Dendritic Spines; Dentate Gyrus; Dopamine; Extinction, Psychological; Male; Memory Disorders; Memory, Short-Term; Nucleus Accumbens; Olanzapine; Prefrontal Cortex; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, GABA-A; Serotonin; Time

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.. 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).. 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).. 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.

Topics: Animals; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Behavior, Animal; Benzodiazepines; Cognition Disorders; Depression; Disease Models, Animal; Drug Administration Schedule; Female; Male; Maze Learning; Memory Disorders; Olanzapine; Piperazines; Pregnancy; Prenatal Exposure Delayed Effects; Quinolones; Rats; Rats, Wistar; Schizophrenia; Stress, Psychological; Time Factors

We investigated the effects of the second generation antipsychotics olanzapine, sertindole and clozapine on visual recognition memory using the novel object recognition (NOR) test in naive and MK-801-treated animals. The effects of drug treatment on locomotion and anxiety were also determined using the open field test. Male Balb-c mice were treated with olanzapine (0.2, 0.4 and 0.6 mg/kg; i.p.), sertindole (0.63, 1.3 and 2.5mg/kg; s.c.) or clozapine (0.5 and 1mg/kg; i.p.), and cognitive deficits were induced by MK-801 (0.2mg/kg; i.p.) administration. Olanzapine treatment decreased the ratio index in the NOR test, whereas sertindole and clozapine had no effect in naive mice. MK-801-induced cognitive impairment was reversed by treatment with olanzapine, sertindole or clozapine. While olanzapine, sertindole and clozapine had no effect on the anxiety of naive mice as determined by the open field test, MK-801 significantly increased the total distance traveled, time spent in the center zone and the velocity of the animals. MK-801-induced effects on locomotion and anxiety in the open field test were reversed by olanzapine, sertindole or clozapine treatment. The results of the present study demonstrated that olanzapine, sertindole and clozapine improved cognition in MK-801 treated mice, and indicate that these drugs have a potential to improve cognition in schizophrenia.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Imidazoles; Indoles; Learning; Male; Memory Disorders; Mice; Mice, Inbred BALB C; Motor Activity; Olanzapine; Recognition, Psychology; Visual Perception

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.

Topics: Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Dose-Response Relationship, Drug; Male; Maze Learning; Memory; Memory Disorders; Mice; Mice, Inbred BALB C; Olanzapine

Topics: Adult; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Drug Therapy, Combination; Humans; Male; Memory Disorders; Olanzapine; Piperazines; Psychotic Disorders; Quinolones; Treatment Outcome

Even though memory dysfunction is not considered to be a diagnostic criterion for schizophrenia, results of a neuropsychological research indicate significant damage in mnestic functioning, especially in verbal memory (Saykin et al. 1991). This type of a disorder is recorded in patients with a first episode of schizophrenia, as well as in chronic patients (Saykin et al. 1994). These researches show that this deficit is not influenced by neuroleptics. Paulsen and associates suggest that the deficit of verbal learning in schizophrenia is related to difficulties in encoding retrieving information without significant storage (rapid forgetting) problems (Paulsen at al. 1995). We will present a case of a 36 - year old male who is suffering from a paranoid schizophrenia.

Topics: Antipsychotic Agents; Attention; Benzodiazepines; Follow-Up Studies; Humans; Long-Term Care; Male; Memory Disorders; Olanzapine; Retention, Psychology; Schizophrenia, Paranoid; Social Behavior; Verbal Behavior; Wechsler Scales; Young Adult

Cannabis is the most widely used illicit substance. Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive impairment that closely resembles the impairment observed in schizophrenic patients. THC has also been known to impair spatial memory in rats tested in the eight-arm radial maze. We previously reported that microinjection of THC (20 microg/side) into the rat dorsal hippocampus impaired spatial memory and that i.p. injection of THC (6 mg/kg) decreased the extracellular levels of acetylcholine (ACh) in the dorsal hippocampus. In the present study, we compared the effects of olanzapine, an atypical antipsychotic, with those of haloperidol, a typical neuroleptic, on the impairments of spatial memory and decreased ACh levels induced by THC (6 mg/kg, i.p.) in rats. We found that olanzapine (0.1 mg/kg, i.p.) reversed the THC-induced memory deficits and decrease in extracellular ACh levels, whereas haloperidol (0.03-0.3 mg, i.p.) had no effect. These results suggest that olanzapine may improve the THC-induced impairment of spatial memory, partly by enhancing ACh release in the dorsal hippocampus. Therefore, olanzapine could attenuate the acute short-term and working memory deficits induced by cannabis.

Topics: Acetylcholine; Animals; Antipsychotic Agents; Behavior, Animal; Benzodiazepines; Cognition Disorders; Dronabinol; Extracellular Space; Hallucinogens; Haloperidol; Hippocampus; Humans; Male; Marijuana Abuse; Maze Learning; Memory Disorders; Microdialysis; Olanzapine; Rats; Rats, Wistar

A novel series of arylsulfonamides was prepared either by automated parallel or by traditional solution-phase synthesis. Several members of this compound library were identified as high-affinity dopamine D3 and D2 receptor ligands. The most interesting representative, compound 2, showed potent antipsychotic behaviour coupled with a beneficial cognitive and EPS profile.

Topics: Animals; Antipsychotic Agents; Apomorphine; Avoidance Learning; Binding, Competitive; Biological Availability; Brain; Catalepsy; Cognition; Humans; Indicators and Reagents; Male; Maze Learning; Memory Disorders; Quantitative Structure-Activity Relationship; Rats; Rats, Wistar; Receptors, Dopamine D2; Receptors, Dopamine D3; Stereotyped Behavior; Sulfonamides

It is hypothesized that olanzapine, an atypical antipsychotic drug, has beneficial effects on cognitive impairment and neuropathological changes in treating neurodegenerative diseases. In the present study, we investigated the effects of chronic administration of olanzapine on the spatial memory impairment and hippocampal cell death induced by the direct injection of okadaic acid (OA), a potent neurotoxin, into the rat hippocampus. After being pretreated with olanzapine (0.5 or 2 mg/kg/day, i.p.) for 2 weeks, the rats were unilaterally microinjected with OA (100 ng) into the hippocampus, and then were continuously administrated with olanzapine for an additional week The rats were trained on a spatial memory task in an eight-arm radial maze before OA administration, and tested on the same task 18 h after the last olanzapine injection. After the behavioral test, the rats were killed for Nissl staining and terminal deoxynucleutidyl transferase-mediated biotinylated UTP nick end labeling staining. OA significantly induced spatial memory impairment, and caused pyramidal cell loss in the CAI and apoptotic cell death in the hippocampus. Olanzapine significantly attenuated OA-induced spatial memory impairment and the OA-induced neuropathological changes in the hippocampus. These findings suggest that olanzapine may have therapeutic effects in treatment of cognitive impairment and neuropathological changes of schizophrenia and other neurodegenerative diseases.

Topics: Analysis of Variance; Animals; Behavior, Animal; Benzodiazepines; Cell Count; Cell Death; Dose-Response Relationship, Drug; Drug Interactions; Hippocampus; In Situ Nick-End Labeling; Male; Maze Learning; Memory Disorders; Microinjections; Motor Activity; Okadaic Acid; Olanzapine; Rats; Rats, Sprague-Dawley; Selective Serotonin Reuptake Inhibitors; Spatial Behavior; Statistics as Topic

Cognitive dysfunction is increasingly considered to be the strongest clinical predictor of poor long-term outcome in schizophrenia. Associations have been found between the severity of cognitive deficits and social dysfunction, impairments in independent living, occupational limitations, and disturbances in quality of life (QOL).. In this cross-sectional study, the relationships of cognitive deficits and treatment outcomes in terms of QOL, needs, and psychosocial functioning were examined in 60 outpatients with schizophrenia who had a duration of illness over 2 years and had been treated with either clozapine or olanzapine for at least 6 months.. The present study suggests that cognitive functioning might be a predictor of work functioning/independent living outcome in stabilized patients with schizophrenia: deficits of visual memory and working memory were negatively associated with occupational functioning, and older patients lived independently and/or in a stable partnership more often. The patients' assessments of QOL and needs for care did not show any significant associations with cognitive functioning.. These findings suggest that cognitive functioning is a key determinant of work functioning/independent living for stable outpatients with schizophrenia.

Topics: Adult; Age Factors; Antipsychotic Agents; Benzodiazepines; Clozapine; Cognition; Cognition Disorders; Comorbidity; Cross-Sectional Studies; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Olanzapine; Outpatients; Predictive Value of Tests; Quality of Life; Schizophrenia; Schizophrenic Psychology; Treatment Outcome