Perseverative Responses Research Articles

Sertindole restores attentional performance and suppresses glutamate release induced by the NMDA receptor antagonist CPP

Blockade of N-methyl-d-aspartic acid (NMDA) receptors in the rat medial prefrontal cortex (mPFC) impairs performance in the five-choice serial reaction time task (5-CSRTT) and increases glutamate (GLU) release. Recent research suggests that excessive GLU release may be critical for attention deficits. We tested this hypothesis by investigating the effects of the atypical antipsychotics sertindole and clozapine on 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP)-induced performance deficits in the 5-CSRTT and on the CPP-induced GLU release in the mPFC. The 5-CSRTT, a test of divided and sustained visual attention providing indices of attentional functioning (accuracy of visual discrimination), response control (anticipatory and perseverative responses) and intracortical microdialysis in conscious rats were used to investigate the effects of sertindole and clozapine. Low doses of sertindole (0.02-0.32mg/kg) prevented CPP-induced accuracy deficits, anticipatory over-responding and the rise in GLU release. In contrast, doses ranging from 0.6 to 2.5mg/kg had no effect or even enhanced the effect of CPP on anticipatory responding. Similarly, 2.5mg/kg sertindole was unable to reverse CPP-induced rise in GLU release. Clozapine (2.5mg/kg) prevented accuracy deficits and the increase in anticipatory responding and abolished the rise in GLU release induced by CPP. These findings show that the ameliorating effects of sertindole and clozapine on NMDA receptor dependent attention deficit is associated with suppression in GLU release in the mPFC. This supports the proposal that suppression in GLU release might be a target for the development of novel drugs aimed at counteracting some aspects of cognitive deficits of schizophrenia.

Effects of aripiprazole, olanzapine, and haloperidol in a model of cognitive deficit of schizophrenia in rats: relationship with glutamate release in the medial prefrontal cortex

Disruption in cognition is characteristic of psychiatric illnesses such as schizophrenia. Studies of drugs that improve cognition might provide a better insight into the mechanisms underlying cognitive deficits. We compared the effects of the antipsychotic drugs aripiprazole, olanzapine, and haloperidol on performance deficit in a test of divided and sustained visual attention, the five-choice serial reaction time task (5-CSRTT), which provides information on attentional functioning (accuracy of visual discrimination), response control (measured by anticipatory and perseverative responses) and speed. The cognitive deficit was induced by infusion of the competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) in the rat medial prefrontal cortex (mPFC). In vivo microdialysis was used to compare the effects of aripiprazole, olanzapine and haloperidol on CPP-induced glutamate (GLU) and serotonin (5-HT) release in the mPFC of conscious rats. Oral aripiprazole (1.0 and 3.0mg/kg) and olanzapine (0.3 and 1.0mg/kg), but not haloperidol (0.1mg/kg), abolished the CPP-induced accuracy deficit and GLU release. Haloperidol and aripiprazole, but not olanzapine, reduced perseverative over-responding, while anticipatory responding was best controlled by olanzapine. However, these effects were not associated with changes in GLU release. No association was found between the effects of these antipsychotics on CPP-induced attentional performance deficits in the 5-CSRTT and 5-HT efflux. The data confirm that excessive GLU release in the mPFC is associated with attentional deficits. Thus, suppression of GLU release may be a target for the development of novel antipsychotic drugs with greater effect on some aspects of cognitive deficits.

주의력결핍 과잉행동장애, 불안장애 아동의 실행기능 비교

Objectives：The purpose of this study was to investigate the deficits in executive function in children with ADHD and anxiety disorder, and further, to characterize executive function deficits among the two groups. Methods：Subjects consisted of 60 children between the ages of 5 and 14 (16 Normal, 24 ADHD, 20 Anxiety Dis-order). Neuropsychological tests (KEDI-WISC, CCTT, STROOP, WCST, ROCF) for assessing cognitive and executive function were individually administered to all subjects. Results：There were no significant differences in FSIQ or PIQ among the three groups. However, the ADHD group tended to score lower on the VIQ and subtest of similarity, vocabulary, and digit span tests. The three groups did not significantly differ with respect to CCTT test results. On the STROOP test, the ADHD group showed poor performance on the word, color, and color-word subtests. The three groups did not exhibit significant differences in WCST test results； however, the anxiety group performed poorly belonging to below 25 percentile rank on perseverative response. On the ROCF test, the ADHD group performed poorly with respect to their organization score and in particular, regarding copy and immediate recall. The anxiety group also performed poorly with regard to organization；however, this was limited only to immediate recall. Conclusion：Children with ADHD displayed poor inhibition and organizational abilities compared to children with anxiety and normal controls. Further, children with anxiety disorder exhibited low cognitive flexibility and voluntary problem-solving abilities compared to ADHD children and normal controls. Based on these results, we suggest that the characteristics of executive dysfunction in ADHD and anxiety disorder in children are different. KEY WORDS：Executive Function·ADHD·Anxiety Disorder.

Sub-optimal performance in the 5-choice serial reaction time task in rats was sensitive to methylphenidate, atomoxetine and d-amphetamine, but unaffected by the COMT inhibitor tolcapone

Prefrontal cortical dopamine (DA) and norepinephrine (NE) are implicated in multiple aspects of cognitive function assessed via the 5-choice serial reaction time task (5-CSRTT) in rodents. The present studies assessed the effects of the NE reuptake inhibitor atomoxetine (0.5–2.0 mg/kg), the mixed DA/NE reuptake inhibitor methylphenidate (0.1–2.0 mg/kg), the catecholamine releaser d-amphetamine (0.1–1.0 mg/kg) and the catecholamine-o-methyl-transferase (COMT) inhibitor tolcapone (3.0–30.0 mg/kg) in rats that exhibited sub-optimal performance (reduced accuracy: <70% correct) in the 5-CSRTT. Increased ITI durations were associated with increased premature responding. Decreased ITI durations resulted in increased percent omissions, increased perseverative responses and increased response latencies, but had no effects on magazine latencies or percent correct. Atomoxetine decreased premature responding at prolonged ITI durations and methylphenidate decreased percent omissions at low doses (0.1 and 0.5 mg/kg). By contrast, d-amphetamine increased premature and perseverative responding in a dose-dependent manner (0.3–1.0 mg/kg). Finally, tolcapone had no effects on sub-optimal performance in the variable ITI 5-CSRTT. These results suggest minimal potential of tolcapone as a therapeutic agent for ADHD and implicate cortical NE, not DA, in impulsive action.

Poor creativity in frontotemporal dementia: A window into the neural bases of the creative mind

BackgroundThe prefrontal cortex (PFC) supports functions critical for creative thinking. Damage to the PFC is expected to impair creativity. Yet, previous works suggested the emergence of artistic talent in patients with frontotemporal lobar degeneration (FTLD), which was interpreted as increased creativity. ObjectiveWe designed a study in patients with frontal variant (fv) of FTLD in order to verify whether: (1) creativity is impaired after frontal degeneration, (2) poor creativity is associated with frontal dysfunctions, and (3) poor creativity is related to hypoperfusion in specific PFC regions. Materials and methodsThree groups of subjects were enrolled in the study: fvFTLD patients (n=17), non-demented Parkinson's disease (PD) patients (n=12) and healthy controls (n=17). Participants performed a standardized test of creativity, the Torrance Test of Creative Thinking (TTCT) and tests assessing frontal functions. Brain perfusion was correlated to fvFTLD patients’ performance in the TTCT. ResultsPatients with fvFTLD were strongly impaired in all dimensions of the TTCT, compared to PD patients and controls. Disinhibited and perseverative responses were observed only in fvFTLD patients, leading to “pseudo-creative” responses. Poor creativity was positively correlated with several frontal tests. Poor creativity was also correlated with prefrontal hypoperfusion, particularly in the frontal pole. ConclusionsPoor creativity is associated with fvFTLD. The results also suggest that the integrity of the PFC (in particular frontopolar) is strongly associated with creative thinking. The emergence of artistic talent in patients with fvFTLD is explained by the release of involuntary behaviors, rather than by the development of creative thinking.

Effects of acute pramipexole on preference for gambling-like schedules of reinforcement in rats

Pramipexole and other direct dopamine agonist medications have been implicated in the development of impulsive behavior such as pathological gambling among those taking the drug to control symptoms of Parkinson's disease or restless leg syndrome. Few laboratory studies examining pramipexole's effects on gambling-like behavior have been conducted. The present study used a rodent model approximating some aspects of human gambling to examine within-subject effects of acute pramipexole (0.03, 0.1, 0.18, and 0.3mg/kg) on rat's choices to earn food reinforcement by completing variable-ratio (VR; i.e., gambling-like) or fixed-ratio (FR) response requirements. In a condition in which the VR alternative was rarely selected, all but the lowest dose of pramipexole significantly increased choice of the VR alternative (an average of 15% above saline). The same doses did not affect choice significantly in a control condition designed to evaluate the involvement of nonspecific drug effects. Pramipexole increased latencies to initiate trials (+9.12s) and to begin response runs on forced-choice trials (VR = +0.21s; FR = +0.88s), but did not affect measures of response perseveration (conditional probabilities of "staying"). The findings are consistent with clinical reports linking pramipexole to the expression of increased gambling in humans. Results are discussed in the context of neurobehavioral evidence suggesting that dopamine agonists increase sensitivity to reward delay and disrupt appropriate feedback from negative outcomes.

G06 Verbal learning and memory in preclinical Huntington's disease

BackgroundHuntington's disease (HD) is associated with progressive cognitive impairments.AimsThe aim of this ongoing study was to examine verbal episodic learning and memory in preclinical HD.MethodsParticipants were recruited from the predictive...

Variation in the Nicotinic Acetylcholine Receptor Gene Cluster CHRNA5–CHRNA3–CHRNB4 and Its Interaction with Recent Tobacco Use Influence Cognitive Flexibility

Variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster have been associated with nicotine dependence (ND) and ND-related traits. To evaluate a potential underlying mechanism for this association, we investigated the effects of 10 variants in this gene cluster and their interactive effects as a result of recent smoking on cognitive flexibility, a possible mediator of genetic effects in smokers. Cognitive flexibility of 466 European Americans (EAs; 360 current smokers) and 805 African Americans (AAs; 635 current smokers) was assessed using the Wisconsin Card Sorting Test. The main effects of variants and haplotypes and their interaction with recent smoking on cognitive flexibility were examined using multivariate analysis of variance and the haplotype analysis program HAPSTAT. In EAs, the major alleles of five variants (CHRNA5-rs3841324-22 bp-insertion-allele, CHRNA5-rs615470-C-allele, CHRNA3-rs6495307-C-allele, CHRNA3-rs2869546-T-allele, and CHRNB4-rs11637890-C-allele) were associated with significantly greater perseverative responses (P=0.003-0.017) and perseverative errors (P=0.004-0.026; recessive effect). Among EAs homozygous for the major alleles of each of these five variants, current smokers made fewer perseverative responses and perseverative errors than did past smokers. Significant interactive effects of four variants (rs3841324, rs615470, rs6495307, and rs2869546) and current smoking on cognitive flexibility were observed (perseverative responses (P=0.010-0.044); perseverative errors (P=0.017-0.050)). However, in AAs, 10 variants in this gene cluster showed no apparent effects on cognitive flexibility. These findings suggest that variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster influences cognitive flexibility differentially in AAs and EAs and that current smoking moderates this effect. These findings could account in part for differences in ND risk associated with these variants in AAs and EAs.

Deep brain stimulation of the nucleus accumbens shell increases impulsive behavior and tissue levels of dopamine and serotonin

The nucleus accumbens (NAc) is gaining interest as a target for deep brain stimulation (DBS) in refractory neuropsychiatric disorders with impulsivity as core symptom. The nucleus accumbens is composed of two subterritories, core and shell, which have different anatomical connections. In animal models, it has been shown that DBS of the NAc changes impulsive action. Here, we tested the hypothesis that a change in impulsive action by DBS of the NAc is associated with changes in dopamine levels. Rats received stimulating electrodes either in the NAc core or shell, and underwent behavioral testing in a reaction time task. In addition, in a second experiment, the effect of DBS of the NAc core and shell on extracellular dopamine and serotonin levels was assessed in the NAc and medial prefrontal cortex. Control subjects received sham surgery. We have found that DBS of the NAc shell stimulation induced more impulsive action but less perseverative checking. These effects were associated with increased levels of dopamine and serotonin in the NAc, but not in the medial prefrontal cortex. DBS of the NAc core had no effect on impulsive action, but decreased perseverative responses indicative of a better impulse control. In these subjects, no effects were found on neurotransmitter levels. Our data point out that DBS of the NAc shell has negative effects on impulsive action which is accompanied by increases of dopamine and serotonin levels in the NAc, whereas DBS of the NAc core has beneficial behavioral effects.

Dopamine agonists increase perseverative instrumental responses but do not restore habit formation in a rat model of Parkinsonism

Dopamine (DA) deafferentation of the dorsolateral striatum has been shown to prevent habit development, leaving instrumental behavior under action–outcome control that is persistently sensitive to modification of the motivational value of the reward. The present experiment further explored the basis of this dysfunction by examining the ability of intrastriatal DA agonist injections (D1 SKF 38393 or D2/D3 Quinpirole) during overtraining of a signaled instrumental task to restore habit formation in rats subjected to bilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal dopaminergic pathway. Overtraining was followed by a test of goal sensitivity by satiety-specific devaluation of the reward. The results confirmed the impaired shift in performance from action to habit in control lesioned rats. However, lesioned rats repeatedly injected with quinpirole D2/D3 agonist showed an increase in non-rewarded instrumental responses (intertrials periods) during overtraining, suggesting the development of perseverative behavior. Following the procedure of devaluation, quinpirole D2/D3 agonist treatment, and to a lesser extent SKF 38393 D1 agonist, caused the persistence of sensitivity to reward devaluation, indicating clear goal-directed behavior despite extended training. This absence of restoration of habit formation by DA agonist treatment is discussed in the light of DA agonist effects in Parkinson patients.

The eyes have it: An exploration of eye movements in action disorganisation syndrome

We examined eye movements in a patient, FK, who has action disorganisation syndrome (ADS), as he performed the everyday task of making a cup of tea. We compared his eye movements with those of a person with Alzheimer's disease and with healthy volunteers. Despite showing very disorganised behaviour many aspects of FK's eye movements were relatively normal. However, unlike normal participants FK made no advance glances to objects that were about to be used, and he made increased numbers of fixations to irrelevant objects during the task. There were also differences in the durations of his eye movements during correct actions and during his perseverative and task-addition responses. We discuss the implications for understanding ADS and the cognitive processes required for correctly performing everyday tasks.

Mental Rotation of Hands in HIV Infection: Neuropsychological Evidence of Dysfunction in Fronto-Striato-Parietal Networks

Mental Rotation of Hands in HIV Infection: Neuropsychological Evidence of Dysfunction in Fronto-Striato-Parietal Networks

“Like déjà vu all over again”: Patterns of perseveration in two people with jargon aphasia

Background: It has been argued that perseveration type corresponds to the level of breakdown, so that total perseveration (repetition of a whole word) involves reactivation of a previous word at the lexical level when the target word is insufficiently activated. A blended perseveration (repetition of part of a previous response) results from a failure of target activation at the phoneme level (e.g., Martin & Dell, 2007). This is challenged by the occurrence of nonword total perseverations, as these cannot be lexical retrievals (Hirsh, 1998). A further problem is the occurrence of long intervals between perseverations and their sources. Some authors have invoked semantic relationships to explain these intervals (e.g., Martin, Roach, Brecher, & Lowery, 1998). Aims: This study examines the perseveration of two individuals with jargon aphasia and explores the proposal that while some perseveration may result from reactivation of recent responses as described above, others are built around default phonology, resulting in stereotypical errors. Methods & Procedures: Tests of naming, reading, and repetition were administered. Responses were analysed to determine: the extent of perseveration; the occurrence of long intervals between perseverations and their sources; patterns of phoneme use; the occurrence of nonword total perseverations. Outcomes & Results: Both individuals produced large numbers of perseverative responses. Perseverative responses following lengthy intervals could not be explained by semantic relationships. For each participant certain consonants were favoured and evidence was found of an interaction between the occurrence of perseveration and these favoured consonants. The possibility that word and nonword total perseverations arose from different sources was rejected because no difference was found in the use of the favoured phonemes in the two types. Conclusions: The findings support the theory of two mechanisms for perseveration. The first is local, occurring when residual activation overrides incoming activation. This is confined to a single utterance and appears closely after the original occurrence. The second type is global, occurring across different contexts over time. It originates from default phonology when incoming activation is unavailable at the phoneme level. Both total and blended perseverations may result from this mechanism. Word total perseverations may be favoured because of feedback from the phoneme level to the lexical level. Ideas for future research and implications for intervention are discussed.

Learning from feedback: Spacing and the delay–retention effect.

Most modern research on the effects of feedback during learning has assumed that feedback is an error correction mechanism. Recent studies of feedback-timing effects have suggested that feedback might also strengthen initially correct responses. In an experiment involving cued recall of trivia facts, we directly tested several theories of feedback-timing effects and also examined the effects of restudy and retest trials following immediate and delayed feedback. Results were not consistent with theories assuming that the only function of feedback is to correct initial errors but instead supported a theoretical account assuming that delaying feedback strengthens initially correct responses due to the spacing of encoding opportunities: Delaying feedback increased the probability of correct response perseveration on the final retention test but had minimal effects on error correction or error perseveration probabilities. In a 2nd experiment, the effects of varying the lags between study, test, and feedback trials during learning provided further support for the spacing hypothesis. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Blockade of serotonin 2A receptors prevents PCP-induced attentional performance deficit and CREB phosphorylation in the dorsal striatum of DBA/2 mice

Functional opposition between N-methyl-D-aspartate and 5-HT(2A) receptors may be a neural mechanism supporting cognitive functions. These systems converge on an intracellular signaling pathway that involves protein kinase A-dependent phosphorylation of different proteins including cyclic adenosine monophosphate response element binding (CREB). Thus, we tested whether selective 5-HT(2A) receptor antagonist, M100907, might abolish phencyclidine (PCP)-induced attentional performance deficit by preventing its effects on transduction mechanisms leading to CREB phosphorylation. Using the five-choice serial reaction time task, the ability of subcutaneous injections of 2.5 and 10 microg/kg of M100907 to abolish the effects of an intraperitoneal injection of 1.5 mg/kg PCP on attentional performance as measured by accuracy (percentage of correct responses) and anticipatory and perseverative responding was assessed in DBA/2 mice. The effects of PCP, M100907, and their combination on S(133)-CREB and T(34)-DARPP32 phosphorylation in the dorsal striatum and prefrontal cortex (PFC) of behaviorally naïve mice were examined using Western blotting technique. PCP reduced accuracy and increased anticipatory and perseverative responses as well as it increased S(133)-CREB phosphorylation in the dorsal striatum but not in the PFC. Ten microg/kg M100907 abolished the PCP-induced attentional performance deficits and the increase in S(133)-CREB but not T(34)-DARPP32 phosphorylation. By itself, M100907 had no effect on attentional performance or phospho-S(133)-CREB and phospho-T(34)-DARPP32. Interestingly, the effect of PCP on phospho-S(133)-CREB but not on phospho-T(34)-DARPP32 was dependent on endogenous 5-HT. The data indicate that blockade of 5-HT(2A) receptors may exert beneficial effects on cognitive deficits through a mechanism linked to striatal S(133)-CREB phosphorylation.

Wisconsin Card Sorting Test performance and impulsivity in patients with temporal lobe epilepsy: Suicidal risk and suicide attempts

Objective: The goal of the study described here was to determine if executive dysfunction and impulsivity are related to risk for suicide and suicide attempts in patients with temporal lobe epilepsy. Method: Forty-two patients with temporal lobe epilepsy were recruited. A detailed medical history, neurological examination, serial EEGs, Mini-International Neuropsychiatric Interview, executive function, and MRI were assessed. Multiple regression analysis was carried out to examine predictive associations between clinical variables and Wisconsin Card Sorting Test measures. Results: Patients’ scores on the Risk for Suicide Scale ( n = 24) were greater than 7, which means they had the highest relative risk for suicide attempts. Family history of psychiatric disease, current major depressive episode, left temporal lobe epilepsy, and perseverative responses and total errors on the Wisconsin Card Sorting Test increased by 6.3 and 7.5 suicide risk and suicide attempts, respectively. Executive dysfunction (specifically perseverative responses and more total errors) contributed greatly to suicide risk. Conclusion: Executive performance has a major impact on suicide risk and suicide attempts in patients with temporal lobe epilepsy.

Individual differences in cognitive control: The role of psychoticism and working memory in set‐shifting

Set-shifting refers to a process of cognitive control which is shown through flexible behavioural adaptation to changes in task parameters or demands, such as the switching of an explicit rule (extra-dimensional rule shifting) or the reversal of a reinforcement-contingency (reversal-learning). Set-shifting deficits are widely documented in specific neuropsychological disorders, but seldom investigated in relation to normally-occurring individual differences. In a sample of healthy adults (N=78, 28% male), we demonstrate that Working Memory and trait Psychoticism have independent involvement in extra-dimensional rule shifting as measured using an analogue of the Wisconsin Card Sorting Test. Only Psychoticism, however, was involved in reversal-learning, as assessed using a recent modification of the Iowa Gambling Task. Individual differences in extra-dimensional rule shifting were explained in terms of rule abstraction speed, while individual differences in reversal-learning were explained in terms of response perseveration. These results clarify component processes in different forms of set-shifting, and highlight the role of individual differences, especially personality, in cognitive control.

Genetic and Environmental Influences on the Wisconsin Card Sorting Test Performance in Healthy Adolescents: A Twin/Sibling Study

This study aimed to estimate the relative contributions from genetic and environmental factors to the Wisconsin Card Sorting Test (WCST) performance, a widely used measurement for assessing frontal lobe function. Participants included 350 pairs of twins (257 MZ and 93 DZ) and 47 same-sex sib-pairs, aged 12-16 years, systematically recruited from junior high schools in Taipei. A computerized version of the WCST was administered for each participant and its nine indexes were used for subsequent analysis. Univariate analysis in structural equation modeling was performed for each WCST index using Mx program. The ACE model for each WCST index indicated no significant genetic influence, whereas the shared environmental influence ranged from 30 to 38% for four indexes (Perseverative Errors, Perseverative Responses, Categories Achieved, and Conceptual Level Responses). We concluded that WCST performance might be an indicator more for environmental insult than for genetic influences on frontal lobe function.

“Pre-semantic” cognition revisited: Critical differences between semantic aphasia and semantic dementia

Patients with semantic dementia show a specific pattern of impairment on both verbal and non-verbal "pre-semantic" tasks, e.g., reading aloud, past tense generation, spelling to dictation, lexical decision, object decision, colour decision and delayed picture copying. All seven tasks are characterised by poorer performance for items that are atypical of the domain and "regularization errors" (irregular/atypical items are produced as if they were domain-typical). The emergence of this pattern across diverse tasks in the same patients indicates that semantic memory plays a key role in all of these types of "pre-semantic" processing. However, this claim remains controversial because semantically impaired patients sometimes fail to show an influence of regularity. This study demonstrates that (a) the location of brain damage and (b) the underlying nature of the semantic deficit affect the likelihood of observing the expected relationship between poor comprehension and regularity effects. We compared the effect of multimodal semantic impairment in the context of semantic dementia and stroke aphasia on the seven "pre-semantic" tasks listed above. In all of these tasks, the semantic aphasia patients were less sensitive to typicality than the semantic dementia patients, even though the two groups obtained comparable scores on semantic tests. The semantic aphasia group also made fewer regularization errors and many more unrelated and perseverative responses. We propose that these group differences reflect the different locus for the semantic impairment in the two conditions: patients with semantic dementia have degraded semantic representations, whereas semantic aphasia patients show deregulated semantic cognition with concomitant executive deficits. These findings suggest a reinterpretation of single-case studies of comprehension-impaired aphasic patients who fail to show the expected effect of regularity on "pre-semantic" tasks. Consequently, such cases do not demonstrate the independence of these tasks from semantic memory.

Chronic prenatal ethanol exposure increases disinhibition and perseverative responding in the adult guinea pig

Cognitive and behavioural deficits, including increased impulsivity and perseveration, are associated with chronic prenatal ethanol exposure (CPEE) in humans. We tested whether these same deficits occur in the guinea pig after CPEE treatment. Pregnant guinea pigs received oral administration of ethanol (4 g/kg maternal body weight/day), or isocaloric-sucrose/pair-feeding throughout gestation. Young adult offspring were trained in lever-pressing paradigms to work for a sucrose-pellet food reward. CPEE increased No-Go, but not Go, responses in the Go/No-Go paradigm, indicative of a disinhibition deficit in these animals. Perseverative responses in the Cued Alternation task were also increased in CPEE offspring. These data show that CPEE induces behavioural deficits in the guinea pig that are remarkably similar to the executive function deficits that follow prenatal ethanol exposure in humans.