Risperidone and the 5-HT2A Receptor Antagonist M100907 Improve Probabilistic Reversal Learning in BTBR T?+?tf/J Mice / Dionisio A. AMODEO in Autism Research, 7-5 (October 2014)  

Public ISBD [article]  inAutism Research > 7-5 (October 2014) . - p.555-567 Titre : Risperidone and the 5-HT2A Receptor Antagonist M100907 Improve Probabilistic Reversal Learning in BTBR T?+?tf/J Mice Type de document : Texte imprimé et/ou numérique Auteurs : Dionisio A. AMODEO, Auteur ; Joshua H. JONES, Auteur ; John A. SWEENEY, Auteur ; Michael E. RAGOZZINO, Auteur Article en page(s) : p.555-567 Langues : Anglais (eng) Mots-clés : autism  cognitive flexibility  BTBR  reversal learning  serotonin  risperidone Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with restricted interests and repetitive behaviors (RRBs). RRBs can severely limit daily living and be particularly stressful to family members. To date, there are limited options for treating this feature in ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in ASD, but less is known about whether it is effective in treating “higher order” RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor targets in which only a subset may be procognitive and others induce cognitive impairment. 5HT2A receptor blockade represents one promising and more targeted approach, as various preclinical studies have shown that 5HT2A receptor antagonists improve cognition. The present study investigated whether risperidone and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal learning performance in the BTBR T?+?tf/J (BTBR) mouse model of autism. The effects of these treatments were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, similar to one in which ASD individuals exhibit impairments, both risperidone (0.125?mg) and M100907 (0.01 and 0.1?mg) improved reversal learning in BTBR mice. Risperidone (0.125?mg) impaired reversal learning in B6 mice. Improvement in probabilistic reversal learning performance resulted from treatments enhancing the maintenance of the newly correct choice pattern. Because risperidone can lead to unwanted side effects, treatment with a specific 5HT2A receptor antagonist may improve cognitive flexibility in individuals with ASD while also minimizing unwanted side effects. Autism Res 2014, 7: 555–567. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1395 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=241 [article] Risperidone and the 5-HT2A Receptor Antagonist M100907 Improve Probabilistic Reversal Learning in BTBR T?+?tf/J Mice [Texte imprimé et/ou numérique] / Dionisio A. AMODEO, Auteur ; Joshua H. JONES, Auteur ; John A. SWEENEY, Auteur ; Michael E. RAGOZZINO, Auteur . - p.555-567. Langues : Anglais (eng) in Autism Research > 7-5 (October 2014) . - p.555-567 Mots-clés : autism  cognitive flexibility  BTBR  reversal learning  serotonin  risperidone Index. décimale : PER Périodiques Résumé : Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social interactions with restricted interests and repetitive behaviors (RRBs). RRBs can severely limit daily living and be particularly stressful to family members. To date, there are limited options for treating this feature in ASD. Risperidone, an atypical antipsychotic, is approved to treat irritability in ASD, but less is known about whether it is effective in treating “higher order” RRBs, for example cognitive inflexibility. Risperidone also has multiple receptor targets in which only a subset may be procognitive and others induce cognitive impairment. 5HT2A receptor blockade represents one promising and more targeted approach, as various preclinical studies have shown that 5HT2A receptor antagonists improve cognition. The present study investigated whether risperidone and/or M100907, a 5HT2A receptor antagonist, improved probabilistic reversal learning performance in the BTBR T?+?tf/J (BTBR) mouse model of autism. The effects of these treatments were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, similar to one in which ASD individuals exhibit impairments, both risperidone (0.125?mg) and M100907 (0.01 and 0.1?mg) improved reversal learning in BTBR mice. Risperidone (0.125?mg) impaired reversal learning in B6 mice. Improvement in probabilistic reversal learning performance resulted from treatments enhancing the maintenance of the newly correct choice pattern. Because risperidone can lead to unwanted side effects, treatment with a specific 5HT2A receptor antagonist may improve cognitive flexibility in individuals with ASD while also minimizing unwanted side effects. Autism Res 2014, 7: 555–567. © 2014 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1395 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=241

The adenosine A2A receptor agonist, CGS 21680, attenuates a probabilistic reversal learning deficit and elevated grooming behavior in BTBR mice / Dionisio A. AMODEO in Autism Research, 11-2 (February 2018)  

Public ISBD [article]  inAutism Research > 11-2 (February 2018) . - p.223-233 Titre : The adenosine A2A receptor agonist, CGS 21680, attenuates a probabilistic reversal learning deficit and elevated grooming behavior in BTBR mice Type de document : Texte imprimé et/ou numérique Auteurs : Dionisio A. AMODEO, Auteur ; Laura CUEVAS, Auteur ; Jeffrey T. DUNN, Auteur ; John A. SWEENEY, Auteur ; Michael E. RAGOZZINO, Auteur Année de publication : 2018 Article en page(s) : p.223-233 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Restricted interests and repetitive behaviors (RRBs) are a defining feature of autism spectrum disorder (ASD). To date there are limited options for treating this core symptomology. Treatments that stimulate adenosine A2A receptors may represent a promising approach for reducing RRBs in ASD. This is because A2A receptors are expressed on striatal neurons of the basal ganglia indirect pathway. Under activation of this pathway has been associated with RRBs while activation of A2A receptors leads to increased activity of the indirect basal ganglia pathway. The present studies investigated whether acute, systemic treatment with CGS21680, an A2A receptor agonist attenuates elevated self?grooming and a probabilistic reversal learning deficit in the BTBR T+ Itpr3tf/J (BTBR) mouse model of idiopathic autism. The effects of this treatment were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, comparable to one in which ASD individuals exhibit deficits, CGS 21680 (0.005 and 0.01mg/kg) attenuated a reversal learning deficit in BTBR mice. Enhancement in probabilistic reversal learning performance resulted from CGS 21680 improving the consistent maintenance of new adaptive behavioral choice patterns after reversal. CGS 21680 at 0.01 mg, but not 0.005 mg, also reduced self?grooming behavior in BTBR mice. CGS 21680 did not affect self?grooming or reversal learning in B6 mice. These findings demonstrate that A2A receptor agonists may be a promising receptor target in the treatment of RRBs in ASD. Autism Res 2018, 11: 223–233. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The present experiments determined whether the drug, CGS 21680, that facilitates activation of adenosine A2A receptors in the brain, would reduce repetitive and inflexible behaviors in the BTBR mouse model of idiopathic autism. CGS 21680 treatment in BTBR mice reduced repetitive and inflexible behaviors. In the control C57BL/6J (B6) mouse strain, CGS 21680 did not affect performance. These findings suggest that stimulation of brain adenosine A2A receptors may be a promising therapeutic strategy in ASD. En ligne : https://doi.org/10.1002/aur.1901 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334 [article] The adenosine A2A receptor agonist, CGS 21680, attenuates a probabilistic reversal learning deficit and elevated grooming behavior in BTBR mice [Texte imprimé et/ou numérique] / Dionisio A. AMODEO, Auteur ; Laura CUEVAS, Auteur ; Jeffrey T. DUNN, Auteur ; John A. SWEENEY, Auteur ; Michael E. RAGOZZINO, Auteur . - 2018 . - p.223-233. Langues : Anglais (eng) in Autism Research > 11-2 (February 2018) . - p.223-233 Index. décimale : PER Périodiques Résumé : Restricted interests and repetitive behaviors (RRBs) are a defining feature of autism spectrum disorder (ASD). To date there are limited options for treating this core symptomology. Treatments that stimulate adenosine A2A receptors may represent a promising approach for reducing RRBs in ASD. This is because A2A receptors are expressed on striatal neurons of the basal ganglia indirect pathway. Under activation of this pathway has been associated with RRBs while activation of A2A receptors leads to increased activity of the indirect basal ganglia pathway. The present studies investigated whether acute, systemic treatment with CGS21680, an A2A receptor agonist attenuates elevated self?grooming and a probabilistic reversal learning deficit in the BTBR T+ Itpr3tf/J (BTBR) mouse model of idiopathic autism. The effects of this treatment were also investigated in C57BL/6J (B6) mice as a comparison strain. Using a spatial reversal learning test with 80/20 probabilistic feedback, comparable to one in which ASD individuals exhibit deficits, CGS 21680 (0.005 and 0.01mg/kg) attenuated a reversal learning deficit in BTBR mice. Enhancement in probabilistic reversal learning performance resulted from CGS 21680 improving the consistent maintenance of new adaptive behavioral choice patterns after reversal. CGS 21680 at 0.01 mg, but not 0.005 mg, also reduced self?grooming behavior in BTBR mice. CGS 21680 did not affect self?grooming or reversal learning in B6 mice. These findings demonstrate that A2A receptor agonists may be a promising receptor target in the treatment of RRBs in ASD. Autism Res 2018, 11: 223–233. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lay Summary The present experiments determined whether the drug, CGS 21680, that facilitates activation of adenosine A2A receptors in the brain, would reduce repetitive and inflexible behaviors in the BTBR mouse model of idiopathic autism. CGS 21680 treatment in BTBR mice reduced repetitive and inflexible behaviors. In the control C57BL/6J (B6) mouse strain, CGS 21680 did not affect performance. These findings suggest that stimulation of brain adenosine A2A receptors may be a promising therapeutic strategy in ASD. En ligne : https://doi.org/10.1002/aur.1901 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=334

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