Jo Neill - Academia.edu (original) (raw)

Papers by Jo Neill

Research paper thumbnail of Sertindole, 5-HT2A and 5-HT6 Antagonists Improve a Subchronic Phencyclidine-Induced Reversal Learning Deficit in Rats

Research paper thumbnail of Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperidone on weight gain, the oestrous cycle and uterine weight in female rats

European Neuropsychopharmacology, Oct 31, 2004

Research paper thumbnail of Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat

Behavioural Brain Research, Nov 1, 2007

Research paper thumbnail of Pregnancy adversely affects ability to recall previously seen spatial locations

Research paper thumbnail of Repeated Phencyclidine (PCP) Increases Impulsivity in the 5-CHOICE Continuous Performance Test in Rats

Research paper thumbnail of Time-Dependent Changes in Gamma Oscillations and Parvalbumin Immunoreactive Cell Density in the CA2/3 Region of the Rat Hippocampus Following Sub-Chronic Phencyclidine Treatment

Research paper thumbnail of Investigation the Role of Dopamine D1 and 5-HT1A Receptors in the Reversal of Sub-Chronic Phencyclidine Induced Deficits in Cognition and Social Behavior, by the Atypical Antipsychotic Clozapine

Research paper thumbnail of Rising endogenous sex steroids adversely affect performance of certain cognitive tasks across pregnancy

Research paper thumbnail of Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats

Behavioural Brain Research 2010 207 144 50, Feb 11, 2010

Research paper thumbnail of Assessment of cognitive function across pregnancy using CANTAB: A longitudinal study

Brain and Cognition a Journal of Experimental and Clinical Research 2013 84 76 84, Dec 1, 2013

Research paper thumbnail of D? receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test

Psychopharmacology 2012 220 129 41, Mar 1, 2012

Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor ... more Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor system has been reported as one of the most promising targets for improving cognition in patients with schizophrenia, with some evidence suggesting D(1) activation may improve sustained attention. The purpose of this study was twofold: firstly assessing the applicability of using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently validated in mice. Secondly, the effect of systemic administration of a D(1) partial agonist, SKF 38393, on task performance during baseline, and a challenge session consisting of a reduced event-rate was investigated. Animals were trained to perform the 5 C-CPT with performance assessed following systemic SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration. Rats could discriminate between target (requiring a response) and non-target (requiring the inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment impaired performance during the baseline session reducing target detection, yet improved performance during the reduced event-rate challenge session, increasing target detection and improving signal discrimination indicating an SKF 38393-induced enhancement of vigilance. Thus, these data suggest that activation of the D(1) system affected 5 C-CPT performance in a baseline dependent manner. Rats can be trained to perform the 5 C-CPT, appropriately withholding from responding to non-target trials. Systemic administration of SKF 38393 impaired performance during baseline conditions. Following a task-related challenge, which reduced the event rate, activation of the dopamine (DA) D(1) system improved performance by heightening the animals' vigilance levels, quantified using signal detection theory.

Research paper thumbnail of Activation of ?7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia

European Neuropsychopharmacology the Journal of the European College of Neuropsychopharmacology 2011 21 333 43, Apr 1, 2011

Research paper thumbnail of The involvement of distraction in memory deficits induced by NMDAR antagonism: relevance to cognitive deficits in schizophrenia

Behavioural Brain Research 2014 266 188 192, 2014

Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be asses... more Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be assessed by the novel object recognition (NOR) task with robust impairments induced by sub-chronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP). The aim of the present study was to investigate how sub-chronic PCP produces its effects in this task. Forty adult female rats received vehicle or PCP (2mg/kg i.p. twice daily for 7 days followed by 7 days washout). Rats completed a 3-min acquisition trial followed by differential inter-trial-interval (ITI) conditions (1 min in the home cage, 10s in the home cage, 1 min in the NOR test box in the presence of an unfamiliar object or 1 min in the NOR test box completely undisturbed) followed by a 3-min retention trial. Control rats spent significantly more time exploring the novel compared with the familiar object in retention. This effect was abolished in the sub-chronic PCP treated animals following all ITI conditions except in rats left completely undisturbed in the NOR test box for a 1 min ITI. The combined influence of sub-chronic PCP treatment and the effect of distraction provides further support for the validity of the NOR test in mimicking cognitive deficits of relevance to schizophrenia.

Research paper thumbnail of Extrasynaptic GABA A receptor activation reverses recognition memory deficits in an animal model of schizophrenia

Psychopharmacology, 2011

Rationale Schizophrenia is a complex psychiatric disorder comprised of three main classes of sym... more Rationale Schizophrenia is a complex psychiatric disorder comprised of three main classes of symptoms: positive, negative and cognitive symptoms. Currently, no approved treatment exists for the cognitive symptoms. There is thus a great need for research aiming at identifying novel targets for treatment of this indication. Several neurotransmitter systems are affected in schizophrenia patients, including the γ-amino butyric acid (GABAergic) system,

Research paper thumbnail of Pregnancy impairs spatial memory and lowers mood

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2010

Research paper thumbnail of Pay attention to impulsivity: Modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats

European Neuropsychopharmacology, 2014

Research paper thumbnail of Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model

European Neuropsychopharmacology, 2014

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attent... more Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation.

Research paper thumbnail of The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania

Expert Opinion on Drug Discovery, 2013

Research paper thumbnail of The involvement of distraction in memory deficits induced by NMDAR antagonism: Relevance to cognitive deficits in schizophrenia

Behavioural Brain Research, 2014

Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be asses... more Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be assessed by the novel object recognition (NOR) task with robust impairments induced by sub-chronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP). The aim of the present study was to investigate how sub-chronic PCP produces its effects in this task. Forty adult female rats received vehicle or PCP (2mg/kg i.p. twice daily for 7 days followed by 7 days washout). Rats completed a 3-min acquisition trial followed by differential inter-trial-interval (ITI) conditions (1 min in the home cage, 10s in the home cage, 1 min in the NOR test box in the presence of an unfamiliar object or 1 min in the NOR test box completely undisturbed) followed by a 3-min retention trial. Control rats spent significantly more time exploring the novel compared with the familiar object in retention. This effect was abolished in the sub-chronic PCP treated animals following all ITI conditions except in rats left completely undisturbed in the NOR test box for a 1 min ITI. The combined influence of sub-chronic PCP treatment and the effect of distraction provides further support for the validity of the NOR test in mimicking cognitive deficits of relevance to schizophrenia.

Research paper thumbnail of Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents

Behavioural Brain Research, 2014

The novel object recognition test (NOR) test is a two trial cognitive paradigm that assesses reco... more The novel object recognition test (NOR) test is a two trial cognitive paradigm that assesses recognition memory. Recognition memory is disturbed in a range of human disorders and NOR is widely used in rodents for investigating deficits in a variety of animal models of human conditions where cognition is impaired. It possesses several advantages over more complex tasks that involve lengthy training procedures and/or food or water deprivation. It is quick to administer, non-rewarded, provides data quickly, cost effective and most importantly, ethologically relevant as it relies on the animal's natural preference for novelty. A PubMed search revealed over 900 publications in rats and mice using this task over the past 3 years with 34 reviews in the past 10 years, demonstrating its increasing popularity with neuroscientists. Although it is widely used in many disparate areas of research, no articles have systematically examined this to date, which is the subject of our review. We reveal that NOR may be used to study recognition memory deficits that occur in Alzheimer's disease and schizophrenia, where research is extensive, in Parkinson's disease and Autism Spectrum Disorders (ASD) where we observed markedly reduced numbers of publications. In addition, we review the use of NOR to study cognitive deficits induced by traumatic brain injury and cancer chemotherapy, not disorders per se, but situations in which cognitive deficits dramatically reduce the quality of life for those affected, see Fig. 1 for a summary. Our review reveals that, in all these animal models, the NOR test is extremely useful for identification of the cognitive deficits observed, their neural basis, and for testing the efficacy of novel therapeutic agents. Our conclusion is that NOR is of considerable value for cognitive researchers of all disciplines and we anticipate that its use will continue to increase due to its versatility and several other advantages, as detailed in this review.

Research paper thumbnail of Sertindole, 5-HT2A and 5-HT6 Antagonists Improve a Subchronic Phencyclidine-Induced Reversal Learning Deficit in Rats

Research paper thumbnail of Effects of the classical antipsychotic haloperidol and atypical antipsychotic risperidone on weight gain, the oestrous cycle and uterine weight in female rats

European Neuropsychopharmacology, Oct 31, 2004

Research paper thumbnail of Atypical antipsychotics attenuate a sub-chronic PCP-induced cognitive deficit in the novel object recognition task in the rat

Behavioural Brain Research, Nov 1, 2007

Research paper thumbnail of Pregnancy adversely affects ability to recall previously seen spatial locations

Research paper thumbnail of Repeated Phencyclidine (PCP) Increases Impulsivity in the 5-CHOICE Continuous Performance Test in Rats

Research paper thumbnail of Time-Dependent Changes in Gamma Oscillations and Parvalbumin Immunoreactive Cell Density in the CA2/3 Region of the Rat Hippocampus Following Sub-Chronic Phencyclidine Treatment

Research paper thumbnail of Investigation the Role of Dopamine D1 and 5-HT1A Receptors in the Reversal of Sub-Chronic Phencyclidine Induced Deficits in Cognition and Social Behavior, by the Atypical Antipsychotic Clozapine

Research paper thumbnail of Rising endogenous sex steroids adversely affect performance of certain cognitive tasks across pregnancy

Research paper thumbnail of Positive modulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors reverses sub-chronic PCP-induced deficits in the novel object recognition task in rats

Behavioural Brain Research 2010 207 144 50, Feb 11, 2010

Research paper thumbnail of Assessment of cognitive function across pregnancy using CANTAB: A longitudinal study

Brain and Cognition a Journal of Experimental and Clinical Research 2013 84 76 84, Dec 1, 2013

Research paper thumbnail of D? receptor activation improves vigilance in rats as measured by the 5-choice continuous performance test

Psychopharmacology 2012 220 129 41, Mar 1, 2012

Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor ... more Impaired attention/vigilance is putatively core to schizophrenia. The dopaminergic D(1) receptor system has been reported as one of the most promising targets for improving cognition in patients with schizophrenia, with some evidence suggesting D(1) activation may improve sustained attention. The purpose of this study was twofold: firstly assessing the applicability of using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently validated in mice. Secondly, the effect of systemic administration of a D(1) partial agonist, SKF 38393, on task performance during baseline, and a challenge session consisting of a reduced event-rate was investigated. Animals were trained to perform the 5 C-CPT with performance assessed following systemic SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration. Rats could discriminate between target (requiring a response) and non-target (requiring the inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment impaired performance during the baseline session reducing target detection, yet improved performance during the reduced event-rate challenge session, increasing target detection and improving signal discrimination indicating an SKF 38393-induced enhancement of vigilance. Thus, these data suggest that activation of the D(1) system affected 5 C-CPT performance in a baseline dependent manner. Rats can be trained to perform the 5 C-CPT, appropriately withholding from responding to non-target trials. Systemic administration of SKF 38393 impaired performance during baseline conditions. Following a task-related challenge, which reduced the event rate, activation of the dopamine (DA) D(1) system improved performance by heightening the animals' vigilance levels, quantified using signal detection theory.

Research paper thumbnail of Activation of ?7 nicotinic receptors improves phencyclidine-induced deficits in cognitive tasks in rats: implications for therapy of cognitive dysfunction in schizophrenia

European Neuropsychopharmacology the Journal of the European College of Neuropsychopharmacology 2011 21 333 43, Apr 1, 2011

Research paper thumbnail of The involvement of distraction in memory deficits induced by NMDAR antagonism: relevance to cognitive deficits in schizophrenia

Behavioural Brain Research 2014 266 188 192, 2014

Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be asses... more Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be assessed by the novel object recognition (NOR) task with robust impairments induced by sub-chronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP). The aim of the present study was to investigate how sub-chronic PCP produces its effects in this task. Forty adult female rats received vehicle or PCP (2mg/kg i.p. twice daily for 7 days followed by 7 days washout). Rats completed a 3-min acquisition trial followed by differential inter-trial-interval (ITI) conditions (1 min in the home cage, 10s in the home cage, 1 min in the NOR test box in the presence of an unfamiliar object or 1 min in the NOR test box completely undisturbed) followed by a 3-min retention trial. Control rats spent significantly more time exploring the novel compared with the familiar object in retention. This effect was abolished in the sub-chronic PCP treated animals following all ITI conditions except in rats left completely undisturbed in the NOR test box for a 1 min ITI. The combined influence of sub-chronic PCP treatment and the effect of distraction provides further support for the validity of the NOR test in mimicking cognitive deficits of relevance to schizophrenia.

Research paper thumbnail of Extrasynaptic GABA A receptor activation reverses recognition memory deficits in an animal model of schizophrenia

Psychopharmacology, 2011

Rationale Schizophrenia is a complex psychiatric disorder comprised of three main classes of sym... more Rationale Schizophrenia is a complex psychiatric disorder comprised of three main classes of symptoms: positive, negative and cognitive symptoms. Currently, no approved treatment exists for the cognitive symptoms. There is thus a great need for research aiming at identifying novel targets for treatment of this indication. Several neurotransmitter systems are affected in schizophrenia patients, including the γ-amino butyric acid (GABAergic) system,

Research paper thumbnail of Pregnancy impairs spatial memory and lowers mood

Archives of Disease in Childhood - Fetal and Neonatal Edition, 2010

Research paper thumbnail of Pay attention to impulsivity: Modelling low attentive and high impulsive subtypes of adult ADHD in the 5-choice continuous performance task (5C-CPT) in female rats

European Neuropsychopharmacology, 2014

Research paper thumbnail of Putative therapeutic targets for symptom subtypes of adult ADHD: D4 receptor agonism and COMT inhibition improve attention and response inhibition in a novel translational animal model

European Neuropsychopharmacology, 2014

Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attent... more Prefrontal cortical dopamine plays an important role in cognitive control, specifically in attention and response inhibition; the core deficits in ADHD. We have previously shown that methylphenidate and atomoxetine differentially improve these deficits dependent on baseline performance. The present study extends this work to investigate the effects of putative therapeutic targets in our model. A selective dopamine D4 receptor agonist (A-412997) and the catechol-O-methyl-transferase (COMT) inhibitor; tolcapone, were investigated in the combined subtype of adult ADHD (ADHD-C). Adult female rats were trained to criterion in the 5C-CPT (5-Choice Continuous Performance Task) and then separated into subgroups according to baseline levels of sustained attention, vigilance, and response disinhibition. The subgroups included: high-attentive (HA) and low-attentive with high response disinhibition (ADHD-C). The ADHD-C subgroup was selected to represent the combined subtype of adult ADHD. Effects of tolcapone (3.0, 10.0, 15.0mg/kg) and A-412997 (0.1, 0.3, 1.0µmol/kg) were tested by increasing the variable inter-trial-interval (ITI) duration in the 5C-CPT. Tolcapone (15mg/kg) significantly increased sustained attention, vigilance and response inhibition in ADHD-C animals, and impaired attention in HA animals. A-412997 (1.0µmol/kg) significantly increased vigilance and response inhibition in ADHD-C animals only, with no effect in HA animals. This is the first study to use the translational 5C-CPT to model the adult ADHD-C subtype in rats and to study new targets in this model. Both tolcapone and A-412997 increased vigilance and response inhibition in the ADHD-C subgroup. D4 and COMT are emerging as important potential therapeutic targets in adult ADHD that warrant further investigation.

Research paper thumbnail of The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania

Expert Opinion on Drug Discovery, 2013

Research paper thumbnail of The involvement of distraction in memory deficits induced by NMDAR antagonism: Relevance to cognitive deficits in schizophrenia

Behavioural Brain Research, 2014

Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be asses... more Recognition memory, impaired in neuropsychiatric conditions and currently untreated, may be assessed by the novel object recognition (NOR) task with robust impairments induced by sub-chronic treatment with the N-methyl-d-aspartate receptor antagonist phencyclidine (PCP). The aim of the present study was to investigate how sub-chronic PCP produces its effects in this task. Forty adult female rats received vehicle or PCP (2mg/kg i.p. twice daily for 7 days followed by 7 days washout). Rats completed a 3-min acquisition trial followed by differential inter-trial-interval (ITI) conditions (1 min in the home cage, 10s in the home cage, 1 min in the NOR test box in the presence of an unfamiliar object or 1 min in the NOR test box completely undisturbed) followed by a 3-min retention trial. Control rats spent significantly more time exploring the novel compared with the familiar object in retention. This effect was abolished in the sub-chronic PCP treated animals following all ITI conditions except in rats left completely undisturbed in the NOR test box for a 1 min ITI. The combined influence of sub-chronic PCP treatment and the effect of distraction provides further support for the validity of the NOR test in mimicking cognitive deficits of relevance to schizophrenia.

Research paper thumbnail of Assessment of disease-related cognitive impairments using the novel object recognition (NOR) task in rodents

Behavioural Brain Research, 2014

The novel object recognition test (NOR) test is a two trial cognitive paradigm that assesses reco... more The novel object recognition test (NOR) test is a two trial cognitive paradigm that assesses recognition memory. Recognition memory is disturbed in a range of human disorders and NOR is widely used in rodents for investigating deficits in a variety of animal models of human conditions where cognition is impaired. It possesses several advantages over more complex tasks that involve lengthy training procedures and/or food or water deprivation. It is quick to administer, non-rewarded, provides data quickly, cost effective and most importantly, ethologically relevant as it relies on the animal's natural preference for novelty. A PubMed search revealed over 900 publications in rats and mice using this task over the past 3 years with 34 reviews in the past 10 years, demonstrating its increasing popularity with neuroscientists. Although it is widely used in many disparate areas of research, no articles have systematically examined this to date, which is the subject of our review. We reveal that NOR may be used to study recognition memory deficits that occur in Alzheimer's disease and schizophrenia, where research is extensive, in Parkinson's disease and Autism Spectrum Disorders (ASD) where we observed markedly reduced numbers of publications. In addition, we review the use of NOR to study cognitive deficits induced by traumatic brain injury and cancer chemotherapy, not disorders per se, but situations in which cognitive deficits dramatically reduce the quality of life for those affected, see Fig. 1 for a summary. Our review reveals that, in all these animal models, the NOR test is extremely useful for identification of the cognitive deficits observed, their neural basis, and for testing the efficacy of novel therapeutic agents. Our conclusion is that NOR is of considerable value for cognitive researchers of all disciplines and we anticipate that its use will continue to increase due to its versatility and several other advantages, as detailed in this review.