- Email: [email protected]
P.1.g.010 The effects of the atypical antipsychotics aripiprazole and olanzapine on learning and memory in naïve rats
S194
P.1.g. Basic and clinical neuroscience − Neuropharmacology
GnRHa treatment to establish the down-regulated state are needed to elucidate SERT and 5-HT2A binding responses to a combined transient ovarian hormone elevation followed by a decline.
P.1.g.010 The effects of the atypical antipsychotics aripiprazole and olanzapine on learning and memory in na¨ıve rats M. Topolov1 ° , D. Getova1 1 Medical University, Department of Pharmacology, Plovdiv, Bulgaria Purpose: Aripiprazole (ARI) is a new antipsychotic drug, which is an alternative to current antipsychotic drugs that adversely affect cognitive processes [1]. Atypical antipsychotic olanzapine (OLZ) acts as dopamine, serotonin and muscarinic antagonist and these transmitters could account for memory impairment in working memory tasks [2]. Our aim was to assess the impact of ARI and olanzapine on behavioral functions of rats with particular emphasis on memory after multiple dosing. Methods: Male Wistar rats (n = 8), divided in 6 groups were treated intraperitoneally (i.p.) with: 1st saline (controls) 0.1 ml/100 g; 2nd and 3rd with ARI 1 mg/kg and 3 mg/kg respectively; 4th , 5th and 6th with OLZ − 0.5 mg/kg, 1 mg/kg and 2 mg/kg respectively. For active avoidance test rats were trained in an automatic reflex conditioner (shuttle box) with 5 days learning session and on the 12th day a memory retention test. The following parameters were observed: number of avoidances, number of escapes from foot shock and number of inter-trial crossings. For passive avoidance tests step through and step down set up were used. Passive avoidance tests were performed in 2 days learning session, and short (3rd day) and long (9th day) memory retention tests. Criteria for step through test were latency of reactions 180 s staying in the light chamber and for step down test was the maximal latency of reaction 60 s staying on the platform. The statistic evaluation was done by ANOVA. Results: In active avoidance test the control rats significantly increased the number of avoidances on learning and memory retention, compared to the 1st day. Rats with ARI decreased the number of avoidances on learning session and on memory retention test, compared to the controls. Rats with OLZ decreased the number of avoidances on 4th and 5th days on learning session and on memory retention test, compared to the controls. All groups of rats did not change the number of escapes and the number of inter-trial crossings during learning and memory tests. In stepthrough passive avoidance test controls increased the latency time on short and long memory retention tests. Rats with ARI increased the latency time during learning and long memory retention test, compared to the controls. Rats with OLZ increased the latency time on the learning session and on the long memory retention test, compared to the controls. In step-down passive avoidance test controls showed increased latency time on 2nd day of learning, and on memory retention tests, compared to the 1st day. ARI increased the latency time in 2 days of learning session, but did not change it in memory retention tests, compared to the control. OLZ increased the latency time on 1st day of learning, but did not change it during memory tests, compared to the controls. Conclusion: The study reveals that antipsychotic drugs ARI and OLZ impaired learning and memory in active avoidance test, but improved it in both passive avoidance tests, probably due to general improvement of cognitive functioning in the hippocampus and prevent some aspects of attention deficit [3].
References [1] Burda, K., Czubak, A., Kus, K., et al, 2011 Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats. Pharmacological reports 63, 898–907. [2] Ortega-Alvaro, A., Gibert-Rahola, J., Mico, J., 2006 Influence of chronic treatment with olanzapine, clozapine and scopolamine on performance of a learned 8-arm radial maze task in rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry 30, 104–111. [3] Carli M, Calgano E, Mainolfi P et al, 2011 Effects of aripiprazole, olanzapine and haloperidol on a model of cognitive deficit in schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex. Psychopharmacology, 214: 639–652.
P.1.g.011 Effect of chronic fluoxetine treatment on subthalamic nucleus and catalepsy in the rat L. Ugedo1 ° , T. Morera-Herreras1 , J.A. Ruiz-Ortega1 , I. Vidaurrazaga1 , C. Miguelez1 , A. Aristieta1 1 University of the Basque Country, Dept. of Pharmacology, Leioa − Bizkaia, Spain So far, several reports have highlighted the interaction between the serotonergic system and motor behavior in humans. Indeed, chronic treatment with selective serotonin reuptake inhibitors, such as fluoxetine, can induce extrapyramidal side effects (e.g., tardive dyskinesia or parkinsonism), akathisia and/or dystonia. These side effects have been suggested to occur because chronic serotonin transporter blockage alters the functionality of the basal ganglia circuits whose nuclei coordinate motor function. Within the basal ganglia, the subthalamic nucleus (STN) is the only glutamatergic structure and participates in motor, associative and limbic functions. In the rat, the STN receives serotonergic input from the dorsal raphe nucleus, expresses serotonergic receptors and in consequence, its activity has been proved to be controlled at least in part by serotonin. The purpose of this study was to evaluate the possible impact of fluoxetine chronic treatment on motor behavior and STN activity using electrophysiological and behavioral approaches in rats. To that end, animals were treated with saline or fluoxetine (10 mg/kg) for 14 days. On the course of the chronic treatment, motor balance, coordination and cataleptic behavior were evaluated using the rotarod and catalepsy test. Both tests were performed on days 1st , 5th , 9th and 14th after the beginning of the treatment. On the same testing session, three evaluations were carried out, just before, 30 and 60 min after saline or fluoxetine administration. Twenty-four hours after the last fluoxetine or saline administration and using in vivo single-cell extracellular recordings, STN activity was evaluated in basal conditions and after a challenge with accumulated doses of fluoxetine. Additionally, changes in the sensitivity of 5-HT1A and 5-HT2C in the STN after fluoxetinechronic administration were also studied. We observed that a challenge of fluoxetine did not change the spontaneous activity of STN neurons from animals treated with saline but increased STN neuron activity of chronic fluoxetine treated rats. We also found that chronic fluoxetine treatment did not modify the basal activity of STN neurons or the response to local application of 5-HT1A and 5-HT2C receptor agonists in the STN. This suggests that chronic fluoxetine treatment does not change the sensitivity of postsynaptic 5-HT1A and 5-HT2C receptors in STN neurons. At the behavioral level, we found that chronic fluoxetine treatment did not impair motor coordination and balance in rats, although it induced marked catalepsy. We also observed that fluoxetine had an anorexigenic effect of the treated rats.
P.1.g. Basic and clinical neuroscience − Neuropharmacology
GnRHa treatment to establish the down-regulated state are needed to elucidate SERT and 5-HT2A binding responses to a combined transient ovarian hormone elevation followed by a decline.
P.1.g.010 The effects of the atypical antipsychotics aripiprazole and olanzapine on learning and memory in na¨ıve rats M. Topolov1 ° , D. Getova1 1 Medical University, Department of Pharmacology, Plovdiv, Bulgaria Purpose: Aripiprazole (ARI) is a new antipsychotic drug, which is an alternative to current antipsychotic drugs that adversely affect cognitive processes [1]. Atypical antipsychotic olanzapine (OLZ) acts as dopamine, serotonin and muscarinic antagonist and these transmitters could account for memory impairment in working memory tasks [2]. Our aim was to assess the impact of ARI and olanzapine on behavioral functions of rats with particular emphasis on memory after multiple dosing. Methods: Male Wistar rats (n = 8), divided in 6 groups were treated intraperitoneally (i.p.) with: 1st saline (controls) 0.1 ml/100 g; 2nd and 3rd with ARI 1 mg/kg and 3 mg/kg respectively; 4th , 5th and 6th with OLZ − 0.5 mg/kg, 1 mg/kg and 2 mg/kg respectively. For active avoidance test rats were trained in an automatic reflex conditioner (shuttle box) with 5 days learning session and on the 12th day a memory retention test. The following parameters were observed: number of avoidances, number of escapes from foot shock and number of inter-trial crossings. For passive avoidance tests step through and step down set up were used. Passive avoidance tests were performed in 2 days learning session, and short (3rd day) and long (9th day) memory retention tests. Criteria for step through test were latency of reactions 180 s staying in the light chamber and for step down test was the maximal latency of reaction 60 s staying on the platform. The statistic evaluation was done by ANOVA. Results: In active avoidance test the control rats significantly increased the number of avoidances on learning and memory retention, compared to the 1st day. Rats with ARI decreased the number of avoidances on learning session and on memory retention test, compared to the controls. Rats with OLZ decreased the number of avoidances on 4th and 5th days on learning session and on memory retention test, compared to the controls. All groups of rats did not change the number of escapes and the number of inter-trial crossings during learning and memory tests. In stepthrough passive avoidance test controls increased the latency time on short and long memory retention tests. Rats with ARI increased the latency time during learning and long memory retention test, compared to the controls. Rats with OLZ increased the latency time on the learning session and on the long memory retention test, compared to the controls. In step-down passive avoidance test controls showed increased latency time on 2nd day of learning, and on memory retention tests, compared to the 1st day. ARI increased the latency time in 2 days of learning session, but did not change it in memory retention tests, compared to the control. OLZ increased the latency time on 1st day of learning, but did not change it during memory tests, compared to the controls. Conclusion: The study reveals that antipsychotic drugs ARI and OLZ impaired learning and memory in active avoidance test, but improved it in both passive avoidance tests, probably due to general improvement of cognitive functioning in the hippocampus and prevent some aspects of attention deficit [3].
References [1] Burda, K., Czubak, A., Kus, K., et al, 2011 Influence of aripiprazole on the antidepressant, anxiolytic and cognitive functions of rats. Pharmacological reports 63, 898–907. [2] Ortega-Alvaro, A., Gibert-Rahola, J., Mico, J., 2006 Influence of chronic treatment with olanzapine, clozapine and scopolamine on performance of a learned 8-arm radial maze task in rats. Progress in Neuro-Psychopharmacology & Biological Psychiatry 30, 104–111. [3] Carli M, Calgano E, Mainolfi P et al, 2011 Effects of aripiprazole, olanzapine and haloperidol on a model of cognitive deficit in schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex. Psychopharmacology, 214: 639–652.
P.1.g.011 Effect of chronic fluoxetine treatment on subthalamic nucleus and catalepsy in the rat L. Ugedo1 ° , T. Morera-Herreras1 , J.A. Ruiz-Ortega1 , I. Vidaurrazaga1 , C. Miguelez1 , A. Aristieta1 1 University of the Basque Country, Dept. of Pharmacology, Leioa − Bizkaia, Spain So far, several reports have highlighted the interaction between the serotonergic system and motor behavior in humans. Indeed, chronic treatment with selective serotonin reuptake inhibitors, such as fluoxetine, can induce extrapyramidal side effects (e.g., tardive dyskinesia or parkinsonism), akathisia and/or dystonia. These side effects have been suggested to occur because chronic serotonin transporter blockage alters the functionality of the basal ganglia circuits whose nuclei coordinate motor function. Within the basal ganglia, the subthalamic nucleus (STN) is the only glutamatergic structure and participates in motor, associative and limbic functions. In the rat, the STN receives serotonergic input from the dorsal raphe nucleus, expresses serotonergic receptors and in consequence, its activity has been proved to be controlled at least in part by serotonin. The purpose of this study was to evaluate the possible impact of fluoxetine chronic treatment on motor behavior and STN activity using electrophysiological and behavioral approaches in rats. To that end, animals were treated with saline or fluoxetine (10 mg/kg) for 14 days. On the course of the chronic treatment, motor balance, coordination and cataleptic behavior were evaluated using the rotarod and catalepsy test. Both tests were performed on days 1st , 5th , 9th and 14th after the beginning of the treatment. On the same testing session, three evaluations were carried out, just before, 30 and 60 min after saline or fluoxetine administration. Twenty-four hours after the last fluoxetine or saline administration and using in vivo single-cell extracellular recordings, STN activity was evaluated in basal conditions and after a challenge with accumulated doses of fluoxetine. Additionally, changes in the sensitivity of 5-HT1A and 5-HT2C in the STN after fluoxetinechronic administration were also studied. We observed that a challenge of fluoxetine did not change the spontaneous activity of STN neurons from animals treated with saline but increased STN neuron activity of chronic fluoxetine treated rats. We also found that chronic fluoxetine treatment did not modify the basal activity of STN neurons or the response to local application of 5-HT1A and 5-HT2C receptor agonists in the STN. This suggests that chronic fluoxetine treatment does not change the sensitivity of postsynaptic 5-HT1A and 5-HT2C receptors in STN neurons. At the behavioral level, we found that chronic fluoxetine treatment did not impair motor coordination and balance in rats, although it induced marked catalepsy. We also observed that fluoxetine had an anorexigenic effect of the treated rats.