Impaired Retrieval Research Articles

Hippocampal \xb5-opioid receptors on GABAergic neurons mediate stress-induced impairment of memory retrieval

Stressful life events induce abnormalities in emotional and cognitive behaviour. The endogenous opioid system plays an essential role in stress adaptation and coping strategies. In particular, the µ-opioid receptor (μR), one of the major opioid receptors, strongly influences memory processing in that alterations in μR signalling are associated with various neuropsychiatric disorders. However, it remains unclear whether μR signalling contributes to memory impairments induced by acute stress. Here, we utilized pharmacological methods and cell-type-selective/non-cell-type-selective μR depletion approaches combined with behavioural tests, biochemical analyses, and in vitro electrophysiological recordings to investigate the role of hippocampal μR signalling in memory-retrieval impairment induced by acute elevated platform (EP) stress in mice. Biochemical and molecular analyses revealed that hippocampal μRs were significantly activated during acute stress. Blockage of hippocampal μRs, non-selective deletion of μRs or selective deletion of μRs on GABAergic neurons (μRGABA) reversed EP-stress-induced impairment of memory retrieval, with no effect on the elevation of serum corticosterone after stress. Electrophysiological results demonstrated that stress depressed hippocampal GABAergic synaptic transmission to CA1 pyramidal neurons, thereby leading to excitation/inhibition (E/I) imbalance in a μRGABA-dependent manner. Pharmaceutically enhancing hippocampal GABAA receptor-mediated inhibitory currents in stressed mice restored their memory retrieval, whereas inhibiting those currents in the unstressed mice mimicked the stress-induced impairment of memory retrieval. Our findings reveal a novel pathway in which endogenous opioids recruited by acute stress predominantly activate μRGABA to depress GABAergic inhibitory effects on CA1 pyramidal neurons, which subsequently alters the E/I balance in the hippocampus and results in impairment of memory retrieval.

Total sleep deprivation impairs fear memory retrieval by decreasing the basolateral amygdala activity

It is well known that sleep deprivation impairs fear memory processes, but little is known about the underlying mechanisms or circuits. The aim of this study was to evaluate the effects of total sleep deprivation (24 h) on contextual fear memory acquisition, consolidation, and retrieval, as well as c-Fos activity in the hippocampus and amygdala. Fear memory recall was associated with an increase in the number of c-Fos-positive cells in the hippocampal CA1 and CA3 regions and the basolateral amygdala (BLA). Total sleep deprivation before to the acquisition and during consolidation of memory impaired retrieval and blocked the associated c-Fos activity in the hippocampus and amygdala. In contrast, total sleep deprivation before memory recall also impaired retrieval, but selectively prevented the increase of c-Fos activity in the amygdala (but not in the hippocampus). Our data indicate that sleep is essential not only for acquisition and consolidation but also for the retrieval of fear memories. They also suggest a differential susceptibility of specific memory-related neural circuits (hippocampus and BLA) to the absence of sleep.

Autobiographical memory in epileptic patients after temporal lobe resection or bitemporal hippocampal sclerosis.

The human hippocampus is believed to be a crucial node in the neural network supporting autobiographical memory retrieval. Structural mesial temporal damage associated with temporal lobe epilepsy (TLE) provides an opportunity to systematically investigate and better understand the local and distal functional consequences of mesial temporal damage in the engagement of the autobiographical memory network. We examined 19 TLE patients (49.21 ± 11.55years; 12 females) with unilateral mesial TLE (MTLE; 12 with anterior temporal lobe resection: 6 right MTLE, 6 left MTLE) or bilateral mesial TLE (7 BMTLE) and 18 matched healthy subjects. We used functional MRI (fMRI) with an adapted autobiographical memory paradigm and a specific neuropsychological test (Autobiographical Memory Interview, AMI). While engaged in the fMRI autobiographical memory paradigm, all groups activated a large fronto-temporo-parietal network. However, while this network was left lateralized for healthy participants and right MTLE patients, left MTLE and patients with BMTLE also showed strong activation in right temporal and frontal regions. Moreover, BMTLE and left MTLE patients also showed significant mild deficits in episodic autobiographical memory performance measured with the AMI test. The right temporal and extra-temporal fMRI activation, along with the impairment in autobiographical memory retrieval found in left MTLE and BMTLE patients suggest that alternate brain areas-other than the hippocampus-may also support this process, possibly due to neuroplastic effects.

The relationship between word retrieval, drawing, and semantics in people with aphasia

ABSTRACTBackground: Word retrieval impairments in aphasia can affect a person’s ability to communicate his or her needs and ideas. Treatment for these deficits typically focuses on restorative and/or compensatory strategies. While traditionally used as a compensatory strategy, emerging evidence suggests that drawing may also have restorative effects on word retrieval by providing an alternate route to accessing the semantic system. However, the current understanding of this theoretical relationship between the semantic system, drawing, and word retrieval abilities is limited.Aims: The study purpose was to examine the relationship among naming, drawing, and semantic feature generation. Additionally, we examined the influence of drawing quality and content, as well as different performances based on aphasia severity.Methods & Procedures: Ten participants with chronic aphasia completed a series of sequenced tasks measuring confrontation naming accuracy before and after drawing and a semantic feature cueing task for target nouns.Outcomes & Results: Participants significantly increased confrontation naming accuracy when they named targets after completing semantic feature cueing then drawing. Additionally, there were moderate negative relationships between semantic content present in participant drawings and drawing quality with the amount of semantic features participants produced.Conclusions: Drawing, combined with a semantic cue task may result in more accurate naming as compared to confrontation naming alone; however, future research is needed to better understand this relationship.

Remembering or knowing how we felt: Depression and anxiety symptoms predict retrieval processes during emotional self-report.

Researchers and clinicians routinely rely on patients' retrospective emotional self-reports to guide diagnosis and treatment, despite evidence of impaired autobiographical memory and retrieval of emotional information in depression and anxiety. To clarify the nature and specificity of these impairments, we conducted two large online data collections (Study 1, N = 1,983; Study 2, N = 900) examining whether depression and/or anxiety symptoms would uniquely predict the use of self-reported episodic (i.e., remembering) and/or semantic (i.e., knowing) retrieval when rating one's positive and negative emotional experiences over different time frames. Participants were randomly assigned to one of six time frames (ranging from at this moment to last few years) and were asked to rate how intensely they felt each of four emotions, anxious, sad, calm, and happy, over that period. Following each rating, they were asked several follow-up prompts assessing their perceived reliance on episodic and/or semantic information to rate how they felt, using procedures adapted from the traditional "remember/know" paradigm (Tulving, 1985). Across both studies, depression and anxiety symptoms each uniquely predicted increased likelihood of remembering across emotion types, and decreased likelihood of knowing how one felt when rating positive emotion types. Implications for the theory and treatment of emotion-related memory disturbances in depression and anxiety, and for dual-process theories of memory retrieval more generally, are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Chronic phencyclidine treatment impairs spatial working memory in rhesus monkeys.

Phencyclidine (PCP) could induce schizophrenia (Sz) like behavior in both humans and animals, therefore, has been widely utilized to establish Sz animal models. It induced cognitive deficits, the core symptom of Sz, mainly through influencing frontal dopaminergic function. Nonhuman primate (NHP) studies demonstrated impaired object retrieval detour (ORD) and spatial delayed response (SDR) task performance by acute or chronic PCP treatment. However, NHP investigations, continually monitoring SDR performance before, during and after PCP treatment, are lacking. Present study investigated the long-term influence of chronic PCP treatment on SDR performance and the possible increase of SDR deficit severity and duration by the incremental dosing procedure in rhesus monkeys. SDR task was performed repeatedly up to eight weeks after constant dosing procedure (i.m., 0.3 mg/kg, day 12-25), during which drug effects on locomotor activity and blood cortisol concentration were assessed. Incremental dosing procedure (starting dose 0.3 mg/kg, day 6-19) began five months later. Constant dosing procedure induced differential level of hyperactivity across testing days, without significant influence on blood cortisol concentration. It reduced SDR performance, until occurrence of the first and worst impairment on day 15 and 23 respectively. The impaired performance recovered to pretreatment level over one week after drug cessation. In contrast, incremental dosing procedure impaired SDR performance on the first treatment day, which recovered within treatment period. Results suggested increase of SDR deficit severity by repeated PCP administrations, whereas the incremental dosing procedure did not increase SDR deficit severity and duration.

Misremembrance of Things Past: Depression Is Associated With Difficulties in the Recollection of Both Specific and Categoric Autobiographical Memories.

Impaired retrieval of specific, autobiographical memories of personally experienced events is characteristic of major depressive disorder (MDD). However, findings in subclinical samples suggest that the reduced specificity phenomenon may reflect a broader impairment in the deliberate retrieval of all autobiographical memory types. This experiment (N = 68) explored this possibility by requiring individuals with and without MDD to complete a cued-recall task that required retrieval of specific, single-incident memories to a block of cues; retrieval of categoric, general memories to a block of cues; and to alternate between retrieval of specific and general memories for a block of cues. Results demonstrated that relative to never-depressed controls, individuals with MDD experience reduced recall of both specific (d = 0.48) and general memories (d = 1.00) along with reduced flexibility in alternating between specific and general memories (d = 0.90). Findings support further development of autobiographical memory–based interventions that target a range of retrieval deficits rather than specificity alone.

Frontal lobe dysfunction underlies the differential word retrieval impairment in adolescents with high-functioning autism.

There is substantial evidence of word retrieval impairment as indicated by poor performance on the category fluency test in autism spectrum disorder (ASD). However, little is known about the neural mechanisms underlying this impairment. Functional neuroimaging studies have shown that the lateral frontal cortex plays a key role in flexible word retrieval. Thus, we examined whether individuals with ASD exhibited altered frontal processing during the category fluency test using functional near-infrared spectroscopy (fNIRS). Twenty-two adolescents with high-functioning ASD (20 males) and 22 typically developing (TD) adolescents (16 males) aged 11-18 years were recruited. All underwent a category fluency paradigm, which required production of animal or means of transportation words for 1 min each although their frontal hemodynamic changes were recorded with fNIRS. We found that adolescents with ASD produced fewer animal but not transportation words (group-by-category interaction: P = 0.003), suggesting differential word retrieval impairment. In addition, unlike TD adolescents who exhibited activation primarily in lateral frontal regions during word production, adolescents with ASD had comparable activation across lateral and medial frontal regions. More importantly, this lack of lateral-medial distinction of activation, which was associated with poor word retrieval, differed significantly between groups only in the animal category (group-by-category interaction: P = 0.018). Thus, our findings implicate frontal lobe dysfunction in the impairment of differential word retrieval in adolescents with ASD. The relatively greater involvement of the medial frontopolar cortex might reflect the use of nonspecialized brain regions to compensate for the category-dependent difficulties with word retrieval in ASD. Autism Res 2019, 12: 600-613. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using an optical imaging tool, we found that adolescents with autism had difficulties with producing semantically related words and exhibited frontal lobe dysfunction. Nonetheless, poor word production and altered brain processing was only seen when these adolescents were asked to produce words from a category of living things but not nonliving things (i.e., animals but not means of transportation). Category-dependent word retrieval problems and frontal lobe dysfunction might be two features of this disorder.

An oral presentation causes stress and memory impairments

Laboratory experiments revealed the stress hormone cortisol to decrease memory retrieval of emotional material, but a translation to real-life settings is missing so far. In this study, 51 students encoded a list of neutral, positive, and negative words as well as two neutral, biographical notes one day before attendance at a seminar at the university. In the stress condition, students gave a graded oral presentation, whereas they just attended the same seminar in the control condition immediately before retrieval took place. Measures of state anxiety, salivary cortisol and alpha-amylase confirmed the oral presentation to constitute a potent stressor. Importantly, stress significantly impaired retrieval of negative words, but not retrieval of the biographical notes. These results indicate that a real-life stressor decreases memory retrieval for negative items. In contrast, delayed memory retrieval of neutral information and interrelated details of biographical notes seems to be less prone to stress effects. These results have critical implications for educational settings.

Acute Stress Facilitates LTD Induction at Glutamatergic Synapses in the Hippocampal CA1 Region by Activating μ-Opioid Receptors on GABAergic Neurons

Acute stress impairs recall memory through the facilitation of long-term depression (LTD) of hippocampal synaptic transmission. The endogenous opioid system (EOS) plays essential roles in stress-related emotional and physiological responses. Specifically, behavioral studies have shown that the impairment of memory retrieval induced by stressful events involves the activation of opioid receptors. However, it is unclear whether signaling mediated by μ-opioid receptors (μRs), one of the three major opioid receptors, participates in acute stress-related hippocampal LTD facilitation. Here, we examined the effects of a single elevated platform (EP) stress exposure on excitatory synaptic transmission and plasticity at the Schaffer collateral-commissural (SC) to CA1 synapses by recording electrically evoked field excitatory postsynaptic potentials and population spikes of hippocampal pyramidal neurons in anesthetized adult mice. EP stress exposure attenuated GABAergic feedforward and feedback inhibition of CA1 pyramidal neurons and facilitated low-frequency stimulation (LFS)-induced long-term depression (LTD) at SC-CA1 glutamatergic synapses. These effects were reproduced by exogenously activating μRs in unstressed mice. The specific deletion of μRs on GABAergic neurons (μRGABA) not only prevented the EP stress-induced memory impairment but also reversed the EP stress-induced attenuation of GABAergic inhibition and facilitation of LFS-LTD. Our results suggest that acute stress endogenously activates μRGABA to attenuate hippocampal GABAergic signaling, thereby facilitating LTD induction at excitatory synapses and eliciting memory impairments.

Muscarinic activity in hippocampus and entorhinal cortex is crucial for spatial and fear memory retrieval.

Hippocampus and entorhinal cortex are key players of learning and memory. Despite their established role in memory processes, the contribution of muscarinic receptor activity in these brain regions during memory retrieval remains elusive. This study was aimed to assess the role of hippocampal CA1 and medial entorhinal cortex muscarinic receptors in memory retrieval. Mice were implanted with bilateral cannulas in the hippocampus CA1 and medial entorhinal cortex. After recovery they were trained for Morris water maze test, novel object recognition test and contextual fear conditioning. Scopolamine was infused 10 min prior to retrieval test. Pre-test scopolamine infusion in hippocampal CA1 and medial entorhinal cortex significantly reduced overall exploration of objects (p<0.001). Similarly, pre-retrieval inactivation dorsal hippocampal CA1 and medial entorhinal cortex muscarinic activity caused significant impairment of spatial and fear memories retrieval (p<0.05). These findings showed vital role of muscarinic activity in retrieving hippocampal and entorhinal cortex dependent memories and suggest a possible target for treating retrograde amnesia.

Are we good judges of our stress? A study of the association between subjective reports of stress and physiological stress markers

Laboratory experiments revealed the stress hormone cortisol to decrease memory retrieval of emotional material, but a translation to real-life settings is missing so far. In this study, 51 students encoded a list of neutral, positive, and negative words as well as two neutral, biographical notes one day before attendance at a seminar at the university. In the stress condition, students gave a graded oral presentation, whereas they just attended the same seminar in the control condition immediately before retrieval took place. Measures of state anxiety, salivary cortisol and alpha-amylase confirmed the oral presentation to constitute a potent stressor. Importantly, stress significantly impaired retrieval of negative words, but not retrieval of the biographical notes. These results indicate that a real-life stressor decreases memory retrieval for negative items. In contrast, delayed memory retrieval of neutral information and interrelated details of biographical notes seems to be less prone to stress effects. These results have critical implications for educational settings.

GORAB scaffolds COPI at the trans-Golgi for efficient enzyme recycling and correct protein glycosylation

COPI is a key mediator of protein trafficking within the secretory pathway. COPI is recruited to the membrane primarily through binding to Arf GTPases, upon which it undergoes assembly to form coated transport intermediates responsible for trafficking numerous proteins, including Golgi-resident enzymes. Here, we identify GORAB, the protein mutated in the skin and bone disorder gerodermia osteodysplastica, as a component of the COPI machinery. GORAB forms stable domains at the trans-Golgi that, via interactions with the COPI-binding protein Scyl1, promote COPI recruitment to these domains. Pathogenic GORAB mutations perturb Scyl1 binding or GORAB assembly into domains, indicating the importance of these interactions. Loss of GORAB causes impairment of COPI-mediated retrieval of trans-Golgi enzymes, resulting in a deficit in glycosylation of secretory cargo proteins. Our results therefore identify GORAB as a COPI scaffolding factor, and support the view that defective protein glycosylation is a major disease mechanism in gerodermia osteodysplastica.

Grammatical Morphology in Aphasia: Evidence from Cantonese Classifiers

Grammatical Morphology in Aphasia: Evidence from Cantonese Classifiers

The effect of facilitation of lexical retrieval on verb phrase production in Primary Progressive Aphasia.

The effect of facilitation of lexical retrieval on verb phrase production in Primary Progressive Aphasia.

Measuring word retrieval in narrative discourse: core lexicon in aphasia.

Discourse analysis procedures are time consuming and impractical in a clinical setting. Critical to clinicians are simple and informative discourse measures that require minimal time and labour to complete. Many studies, however, have overlooked difficulties that clinicians face. We recently developed core lexicon lists for nouns, verbs, adjectives and adverbs for two narrative discourse tasks with healthy control groups. Core lexicon lists consist of important lexical items required to produce coherently meaningful discourse in response to discourse tasks. Measuring core lexicon is useful for quantifying word retrieval impairments at the discourse level in clinical populations. To apply an age-based core lexicon list for nouns, verbs, adjectives and adverbs for the wordless picture books Good Dog Carl (1985) and Picnic (1984) and to determine how well the lists measured linguistic impairments in persons with aphasia (PWA). Lemma forms were extracted from 470 control participants who were divided into seven age groups. Twenty-five core lexicons were identified for four word classes (nouns, verbs, adjectives and adverbs) among the seven age groups. The nouns, verbs, adjectives and adverbs for each PWA (N = 11) were then compared with the core lexicon for their respective age group. Per cent agreement was computed by comparing the number of total items within each list to the number of items that PWA produced. A Spearman's correlation coefficient was computed between the WAB-R AQ and the per cent agreement for each word type for PWA. The percentage of agreement for each word type among the age cohorts ranged between 56% and 96%. Of the four word types, core verbs significantly correlated with the WAB AQs for both discourse tasks. A post-hoc analysis found significant differences between fluent and non-fluent aphasia for core verbs. Core lexicon analysis appears to be a practical way to capture impairments in word retrieval at the discourse level. Core verbs may be a better indicator to understand holistic language performances for PWA. Use of the core lexicon checklist can serve as an option to reconcile ecological validity with clinical usability.

Noun–verb naming dissociation in neurosurgical patients

ABSTRACTBackground: Dissociated impairment of noun and verb retrieval has been frequently reported after vascular brain lesions: selective damage of either grammatical class allowed to test models of lexical processing and of its neuroanatomical foundation. However, vascular lesions are often quite large and do not involve brain structures uniformly. Neurosurgical lesions do not undergo such apparent limitation, being usually smaller and better distributed across the cerebral cortex.Aims: We explored the neuroanatomical correlates of noun–verb naming processing and dissociations by means of the voxel-based lesion symptom mapping (VLSM) procedure and the subtraction of lesion volume of interests (VOIs) approach in a series of 99 neurosurgical patients.Methods and Procedures: The VOIs and behavioral data for noun and verb naming were analyzed in a VLSM procedure. The verb (or noun) naming performance was included as a covariate control variable, which allowed testing effects on noun (or verb) naming, controlling for the verb (or noun) naming performance. The total lesion volume was also included as a covariate to avoid spurious effects.Outcomes and Results: Eighteen patients showed a significant dissociation between noun and verb naming: seven patients showed disproportionate impairment in naming nouns, and eleven patients with disproportionate impairment in naming verbs. In addition, there were 27 undifferentiated patients, i.e. performing abnormally on nouns and/or verbs, but non-dissociating between the two word classes.VLSM in combination with the subtraction of lesion mask analyses revealed that verb naming impairments were related with lesions in the middle frontal gyrus, precentral gyrus, parietal and rolandic operculum, supplementary motor area, and the inferior parietal (supramarginal and angular gyri), whereas noun naming impairments were associated with basal temporo-occipital lesions. Furthermore, data indicate that noun and verb naming deficits also depend on a disconnection phenomenon: at subcortical level, noun naming impairments are related to damage to parts of the sagittal stratum (including the inferior fronto-occipital fasciculus and the inferior longitudinal fasciculus), the splenium of the corpus callosum, the posterior thalamic radiations (plus optic radiations), the retrorolandic part of the internal capsule, the tapetum and the fornix. On the contrary, verb naming impairments are related to damage to parts of the superior and posterior corona radiata, and of the anterior and posterior limb of the internal capsule.Conclusions: Summing up, results point to verb-specific areas in the superior frontal as well as the inferior parietal cortex, and noun-specific basal temporo-occipital and subcortical neural circuitries.

The role of CA1 CB1 receptors on lithium-induced spatial memory impairment in rats.

Lithium, a glycogen synthase kinase-3β (GSK-3β) inhibitor, prevents cannabinoid withdrawal syndrome, but there is limited data exploring the interaction between lithium and cannabinoid system on memory processes. The present study aimed to test the interaction between dorsal hippocampal (CA1 region) cannabinoid system and lithium on spatial memory in rats. Spatial memory was assessed in Morris Water Maze (MWM) apparatus by a single training session of eight trials. The results showed that pre-training intra-CA1 microinjection of ACPA, the cannabinoid type 1 receptor (CB1r) agonist, at doses of 0.001, 0.01 or 1 µg/rat, or AM251, the cannabinoid type 1 receptor (CB1r) antagonist, at doses of 1, 10 or 100 ng/rat, increased escape latency and traveled distance to the platform, suggesting a spatial learning impairment, whereas intraperitoneal administration of lithium (0.5, 1 or 5 mg/kg) had no effect on spatial learning. Also, rats that received lithium plus a lower dose of ACPA (0.001 µg/rat) or AM251 (1 ng/rat) had successful performance in the MWM. In the probe test, the results showed that pre-training administration of lithium (5 mg/kg) and ACPA (0.01 or 1 µg/rat) but not AM251 (at all doses used) impaired spatial memory retrieval. Also, lower dose of ACPA (0.001 µg/rat) or AM251 (1 ng/rat) potentiated the effect of ineffective doses of lithium (0.5 and 1 mg/kg) on spatial memory retrieval, while restored the effect of effective dose of lithium (5 mg/kg). In conclusion, cannabinoids may have a dual effect on lithium-induced spatial memory impairment in rats.

Hypercholesterolemia impairs contextual fear conditioning memory formation in female mice: evidence for cholinergic dysfunction.

The present study evaluated the effects of hypercholesterolemia in response to conditioned aversive stimuli in mice. Specifically, (a) young (3 months old) and aged (24 months old) female C57Bl/6 mice were fed daily for 4 weeks with a standard rodent diet or an enriched cholesterol diet (ECD) and then subjected to the contextual fear conditioning test. In another experimental set, 3-month-old C576Bl/6 female mice, fed daily during the 4 weeks with the standard rodent diet or ECD, were subjected to the contextual fear conditioning test and received vehicle or scopolamine (0.37 mg/kg; intraperitoneally) immediately after the training session. (b) 12-month-old C576Bl/6 and low-density lipoprotein receptor knockout mice (LDLr) female mice were subjected to the contextual fear conditioning test. In another experimental set, they were subjected to the contextual fear conditioning test and received vehicle or donepezil (3.0 mg/kg; intraperitoneally) immediately after the training session. The present results show that (a) the ECD specifically impaired retrieval of contextual fear memory in aged mice; (b) an ineffective dose of scopolamine impaired fear memory consolidation in young mice fed the ECD; (c) LDLr mice presented impaired contextual fear memory retrieval; and (d) boosting cholinergic neurotransmission with a single donepezil administration at the consolidation window led to improved fear memory consolidation in LDLr mice. These findings suggest that high levels of cholesterol induced by either an ECD or a genetic deletion of LDLr decreased freezing behavior on the contextual fear conditioning test, which seemed to involve dysfunction of the cholinergic system.

Potential learning and memory disruptors and enhancers in a simple, 1-day operant task in mice.

The objective of this study was to develop a rapid, 1-day learning and memory assay in mice that is sensitive to the effects of compounds that could impair or enhance acquisition and retrieval. Swiss-Webster, male mice were placed in experimental chambers for a 1-h acquisition session with an intermittent, audible tone. If a nose-poke response occurred during the tone, an Ensure water solution was presented. After 1 h, the mice returned to the chambers for 2 h. Drugs were injected before or after sessions to determine the effects on acquisition and/or retrieval. Mice injected with saline learned a nose-poke response as measured by decreased latencies to earn 10 reinforcers, increased reinforced response rates, and decreased nonreinforced response rates. Scopolamine and acetazolamide impaired retrieval of the nose-poke response, whereas ketamine only modestly impaired retrieval. Doses of 8-OH-DPAT or the novel carbonic anhydrase activator, MAI27, either had no effect or impaired some measures of responding. Neither 8-OH-DPAT nor MAI27 were able to prevent the modest impairments produced by ketamine. The simple, 1-day operant task is a rapid assay that can be used as an initial screen to test the effects of learning and memory disruptors and potentially enhancers.