Active Allothetic Place Avoidance Research Articles

Strategies discovery in the active allothetic place avoidance task

The Active Allothetic Place Avoidance task is an alternative setup to Morris Water Maze that allows studying spatial memory in a dynamic world in the presence of conflicting information. In this task, a rat, freely moving on a rotating circular arena, has to avoid a sector defined within the room frame where shocks are presented. While for Morris Water Maze several studies have identified animal strategies which specifically affect performance, there were no such studies for the Active Allothetic Place Avoidance task. Using standard machine learning methods, we were able to reveal for the first time, to the best of our knowledge, explainable strategies that the animals employ in this task and demonstrate that they can provide a high-level interpretation for performance differences between an animal group treated with silver nanoparticles (AgNPs) and the control group.

Combination of dasatinib and quercetin improves cognitive abilities in aged male Wistar rats, alleviates inflammation and changes hippocampal synaptic plasticity and histone H3 methylation profile.

Aging is associated with cognitive decline and accumulation of senescent cells in various tissues and organs. Senolytic agents such as dasatinib and quercetin (D+Q) in combination have been shown to target senescent cells and ameliorate symptoms of aging-related disorders in mouse models. However, the mechanisms by which senolytics improve cognitive impairments have not been fully elucidated particularly in species other than mice. To study the effect of senolytics on aging-related multifactorial cognitive dysfunctions we tested the spatial memory of male Wistar rats in an active allothetic place avoidance task. Here we report that 8 weeks treatment with D+Q alleviated learning deficits and memory impairment observed in aged animals. Furthermore, treatment with D+Q resulted in a reduction of the peripheral inflammation measured by the levels of serum inflammatory mediators (including members of senescent cell secretome) in aged rats. Significant improvements in cognitive abilities observed in aged rats upon treatment with D+Q were associated with changes in the dendritic spine morphology of the apical dendritic tree from the hippocampal CA1 neurons and changes in the level of histone H3 trimethylation at lysine 9 and 27 in the hippocampus. The beneficial effects of D+Q on learning and memory in aged rats were long-lasting and persisted at least 5 weeks after the cessation of the drugs administration. Our results expand and provide new insights to the existing knowledge associated with effects of senolytics on alleviating age-related associated cognitive dysfunctions.

Silver Nanoparticles Impair Cognitive Functions and Modify the Hippocampal Level of Neurotransmitters in a Coating-Dependent Manner.

Due to their potent antibacterial properties, silver nanoparticles (AgNPs) are widely used in industry and medicine. However, they can cross the brain–blood barrier, posing a risk to the brain and its functions. In our previous study, we demonstrated that oral administration of bovine serum albumin (BSA)-coated AgNPs caused an impairment in spatial memory in a dose-independent manner. In this study, we evaluated the effects of AgNPs coating material on cognition, spatial memory functioning, and neurotransmitter levels in rat hippocampus. AgNPs coated with BSA (AgNPs(BSA)), polyethylene glycol (AgNPs(PEG)), or citrate (AgNPs(Cit)) or silver ions (Ag+) were orally administered at a dose of 0.5 mg/kg b.w. to male Wistar rats for a period of 28 days, while the control (Ctrl) rats received 0.2 mL of water. The acquisition and maintenance of spatial memory related to place avoidance were assessed using the active allothetic place avoidance task, in which rats from AgNPs(BSA), AgNPs(PEG), and Ag+ groups performed worse than the Ctrl rats. In the retrieval test assessing long-term memory, only rats from AgNPs(Cit) and Ctrl groups showed memory maintenance. The analysis of neurotransmitter levels indicated that the ratio between serotonin and dopamine concentration was disturbed in the AgNPs(BSA) rats. Furthermore, treatment with AgNPs or Ag+ resulted in the induction of peripheral inflammation, which was reflected by the alterations in the levels of serum inflammatory mediators. In conclusion, depending on the coating material used for their stabilization, AgNPs induced changes in memory functioning and concentration of neurotransmitters.

Effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on MK-801-induced schizophrenia models.

The adipokinetic and red pigment-concentrating hormone (AKH/RPCH) family of peptides controls fat, carbohydrate, and protein metabolism in insects. In our previous study, we showed that AKH possesses antidepressant, anxiolytic, and analgesic effects, causes hyperlocomotion, and exerts neuroprotective effects and increased brain neurotrophic factors in mice. The aim of this study was to investigate the effects of Anax imperator AKH (Ani-AKH), Libellula auripennis AKH (Lia-AKH), and Phormia-Terra hypertrehalosemic hormone (Pht-HrTH) on MK-801-induced memory deterioration in the active allothetic place avoidance test (AAPA) and MK-801-induced sensorimotor gating deficit in the prepulse inhibition test (PPI). In the AAPA task, Long-Evans rats were treated with Ani-AKH (2mg/kg), Lia-AKH (2mg/kg), Pht-HrTH (2mg/kg), MK-801 (0.15mg/kg), and the combination of MK-801 with the hormones subchronically. In the prepulse inhibition test, Wistar albino rats were treated with Ani-AKH (1mg/kg), Lia-AKH (1mg/kg), Pht-HrTH (1mg/kg), MK-801 (0.1mg/kg), or the combination of MK-801 with hormones acutely before the test. In our study, Ani-AKH (2mg/kg), Lia-AKH (2mg/kg), and Pht-HrTH (2mg/kg) reversed MK-801 (0.15mg/kg)-induced cognitive memory impairment effects in the AAPA task. Lia-AKH (1mg/kg) significantly potentiated the MK-801-induced PPI disruption, while Ani-AKH (1mg/kg) partially potentiated the impairment caused by MK-801, and Pht-HrTH did not modify the effect of MK-801. In conclusion, AKH had no effect in sensorimotor gating deficits in the PPI test in schizophrenia model while AKH improved memory in the schizophrenia model of MK-801.

A Rat Model of Alzheimer's Disease Based on Abeta42 and Pro-oxidative Substances Exhibits Cognitive Deficit and Alterations in Glutamatergic and Cholinergic Neurotransmitter Systems.

Alzheimer’s disease (AD) is one of the most serious human, medical, and socioeconomic burdens. Here we tested the hypothesis that a rat model of AD (Samaritan; Taconic Pharmaceuticals, USA) based on the application of amyloid beta42 (Abeta42) and the pro-oxidative substances ferrous sulfate heptahydrate and L-buthionine-(S, R)-sulfoximine, will exhibit cognitive deficits and disruption of the glutamatergic and cholinergic systems in the brain. Behavioral methods included the Morris water maze (MWM; long-term memory version) and the active allothetic place avoidance (AAPA) task (acquisition and reversal), testing spatial memory and different aspects of hippocampal function. Neurochemical methods included testing of the NR1/NR2A/NR2B subunits of NMDA receptors in the frontal cortex and CHT1 transporters in the hippocampus, in both cases in the right and left hemisphere separately. Our results show that Samaritan rats™ exhibit marked impairment in both the MWM and active place avoidance tasks, suggesting a deficit of spatial learning and memory. Moreover, Samaritan rats exhibited significant changes in NR2A expression and CHT1 activity compared to controls rats, mimicking the situation in patients with early stage AD. Taken together, our results corroborate the hypothesis that Samaritan rats are a promising model of AD in its early stages.

Spatial Memory Using Active Allothetic Place Avoidance in Adult Rats After Isoflurane Anesthesia

We described a paradigm of active allothetic place avoidance (AAPA) as a measure of spatial memory in adult rats. We hypothesized that, pending successful AAPA training, treatment with isoflurane would trigger spatial memory deficits. Fifteen of 20 adult rats were successfully trained and randomly allocated to control and isoflurane treatment groups. An additional 7 animals were used to demonstrate hemodynamic stability during general anesthesia. After training, experimental animals received a 2-hour isoflurane anesthetic. General endotracheal anesthesia was maintained at an isoflurane concentration of 1.8% to 2%. After intervention, retention of training was tested on postanesthesia days 1, 3, and 7. Animals treated with isoflurane displayed selected spatial memory changes up to postanesthesia day 7. There were 2 findings of decreased active avoidance behavior in rats receiving isoflurane: a significant (P=0.029) reduction in maximum path of avoidance in the isoflurane-treated rats compared with controls, and a significant (P=0.038) increase in total path length in the controls. No other measured AAPA parameters achieved statistical significance. Control animals demonstrated increased active avoidance behavior in the AAPA task compared with isoflurane-treated animals. Animals exposed to 2-hour isoflurane general anesthetic had a reduction in the maximum path of avoidance measure up to 7 days postanesthesia, whereas gross spatial parameters such as number of entrances into the shock zone were not significantly different between groups. The AAPA model may prove useful in ascertaining the learning and memory deficits of postoperative cognitive dysfunction.

Cellular and behavioural effects of a new steroidal inhibitor of the N-methyl- d-aspartate receptor 3α5β-pregnanolone glutamate

Preclinical studies have demonstrated a considerable role for N-methyl- d-aspartate (NMDA) receptors in excitotoxicity and the concurrent neuroprotective effect of NMDA receptor antagonists. Because NMDA receptors are one of the most widespread receptors in the central nervous system, application of their antagonist often leads to serious side effects ranging from motor impairment to induction of schizophrenic-like psychosis. Therefore, we have initiated development and testing of a novel synthetic NMDA receptor antagonist derived from naturally occurring neurosteroids. 20-oxo-5β-pregnan-3α-yl- l-glutamyl-1-ester (3α5βP-Glu) is a novel synthetic steroidal inhibitor of the NMDA receptor. Our results show that 3α5βP-Glu preferentially inhibits tonically activated NMDA receptors, is able to cross the blood brain barrier, does not induce psychotomimetic symptoms (such as hyperlocomotion and sensorimotor gating deficit) and reduced an excitotoxic damage of brain tissue and subsequent behavioural impairment in rats. In particular, 3α5βP-Glu significantly ameliorated neuronal damage in the dentate gyrus and subiculum, and improved behavioural performance in active allothetic place avoidance tasks (AAPA, also known as the carousel maze) after bilateral NMDA-induced lesions to the hippocampi. These findings provide a possible new therapeutic approach for the treatment of diseases induced by NMDA receptor overactivation.

The difference in effect of mGlu2/3 and mGlu5 receptor agonists on cognitive impairment induced by MK-801

The manipulation of glutamate neurotransmission could represent a potential strategy for the pharmacotherapy of schizophrenic symptoms. Preclinical studies suggest that two subtypes of metabotropic glutamate (mGlu) receptors such as mGlu2/3 and mGlu5 receptors have the potential to ameliorate deficits in schizophrenia. In our study we evaluated the role of a non-specific mGlu receptor agonist ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid; 1S,3R-ACPD), mGlu5 receptor agonist or positive modulators ((RS)-2-Chloro-5-hydroxyphenylglycine;CHPG; [(3-Fluoro-phenyl)methylene]hydrazone-3-fluorobenzaldehyde; DFB; 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; CDPPB) and a mGlu2/3 receptor agonist (2,2,2-Trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyrdinylmethyl)ethanesulfonamide hydrochloride; LY-487379) on performance in a cognitive task (Active Allothetic Place Avoidance) after sub-chronic administration of 5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imine; MK-801 . The Active Allothetic Place Avoidance task is suitable for assessing the executive function and attention of animals and was previously validated for testing the effect of anti-psychotics. Application of the mGlu2/3 receptor agonist had no effect on cognitive impairment induced by MK-801. However, the mGlu5 receptor agonists ameliorated cognitive impairment induced by MK-801 without affecting locomotion. In conclusion, the mGlu5 receptor agonists could be effective in the treatment of cognitive deficits in patients with schizophrenia. However, the pro-cognitive effect of the agonist of mGlu2/3 receptors was not demonstrated in the present study.

Combined administration of alpha1-adrenoceptor antagonist prazosin and beta-blocker propranolol impairs spatial avoidance learning on a dry arena

Spatial learning is a widely studied type of animal behavior often considered as a model of higher human cognitive functions. Noradrenergic receptors play a modulatory role in many nerve functions, including vigilance, attention, reward, learning and memory. The present study aimed at studying the effects of separate or combined systemic administration of the alpha1-adrenergic antagonist prazosin (1 and 2 mg/kg) and beta-blocker propranolol (5 and 20 mg/kg) on the hippocampus-dependent learning in the active allothetic place avoidance (AAPA) task. Both centrally active drugs impaired spatial learning when administered together, exerting no effect in separate applications. Locomotion was impaired only in a combined application of higher doses of both drugs (2 mg/kg prazosin and 20 mg/kg propranolol). These results suggest an in vivo interaction between these two types of receptors in spatial navigation regulation.

The effect of a full agonist/antagonist of the D1 receptor on locomotor activity, sensorimotor gating and cognitive function in dizocilpine-treated rats

Cognitive impairment has been found across all subtypes of schizophrenia. The location and function of dopamine-1 receptors (D1Rs) make them attractive targets for the treatment of cognitive impairment in schizophrenia. Here we investigate the systemic effect of a D1R agonist (A77636) and antagonist (SCH 23390) on hyperlocomotor activity and cognitive deficit induced by an NMDA receptor antagonist (MK-801). Wistar rats (250-300 g) received A77636 (0.1, 0.5 or 1 mg/kg) or SCH 23390 (0.02 or 0.05 mg/kg) with MK-801 (0.1 mg/kg) or saline for 4 d. On day 4 we assessed the prepulse inhibition of the acoustic startle response, locomotor activity in a novel arena and active allothetic place avoidance (spatial memory task) 15 min after the last injection. Systematic administration of the D1R agonist at 0.1 mg/kg ameliorates cognitive dysfunction in our model of schizophrenia, but increases stereotypy and locomotor activity (model of psychotic symptoms) at higher doses (0.5 or 1 mg/kg). Administration of the D1R antagonist had no effect on cognitive function, but decreased hyperlocomotion induced by MK-801. Thus, based on our results, over-activation of D1Rs may exacerbate psychotic symptoms in patients with schizophrenia.

A dose–response study of the effects of pre-test administration of beta-adrenergic receptor antagonist propranolol on the learning of active place avoidance, a spatial cognition task, in rats

The involvement of various neurotransmitter receptors in the brain in the regulation of spatial behavior is a focus of interest for many cognitive neuroscientists. Active allothetic place avoidance (AAPA) task have been demonstrated to require spatial mapping and cognitive coordination and is highly dependent upon hippocampus. The present study was designed to evaluate the role of beta-adrenergic receptors in the modulation of locomotor and spatial behavior in this task. Four doses of centrally active beta-adrenergic antagonist propranolol (5, 20, 25 and 30 mg/kg) were administered intraperitoneally 30 min prior to testing in the place avoidance task. Four daily sessions were pursued, each lasting 20 min. A dose of 25 mg/kg was found to induce a deficit in spatial behavior (measured by number of entrances into the shock sector) without altering locomotion; lower doses were without effect. The highest dose (30 mg/kg) impaired both locomotion and avoidance behavior. The results suggest that beta-adrenoceptors are involved in the regulation of behavior in the place avoidance task and that it is possible to dissociate the effect of propranolol on the spatial performance and locomotion in the AAPA using dose-selection.

Effect of alpha1-adrenergic antagonist prazosin on behavioral alterations induced by MK-801 in a spatial memory task in Long-Evans rats

Animal models of neuropsychiatric disorders are current topics in behavioral neuroscience. Application of non-competitive antagonists of NMDA receptors (such as MK-801) was proposed as a model of schizophrenia, as it leads to specific behavioral alterations, which are partly analogous to human psychotic symptoms. This study examined an animal model of schizophrenia induced by a systemic application of MK-801 (0.15 and 0.20 mg/kg) into rats tested in the active allothetic place avoidance (AAPA) task. Previous studies suggested that MK-801 may interact in vivo with other neurotransmitter systems, including noradrenergic system. Our experiments therefore evaluated the hypothesis that both locomotor stimulation and deficit in avoidance behavior in AAPA task induced by this drug would be reversible by application of alpha(1)-adrenergic antagonist prazosin (1 and 2 mg/kg). The results showed that both doses of prazosin partially reversed hyperlocomotion induced by higher doses of MK-801 and an avoidance deficit measured as number of entrances into the shock sector. Interestingly, no effect of prazosin on the MK-801-induced decrease of maximum time between two entrances (another measure of cognitive performance) was observed. These results support previous data showing that prazosin can compensate for the hyperlocomotion induced by MK-801 and newly show that this partial reduction sustains even in the forced locomotor conditions, which are involved in the AAPA task. The study also shows that certain parameters of avoidance efficiency may be closely related to locomotor activity, whereas other measures of cognition may more selectively reflect cognitive changes.

P.1.c.001 An ethopharmacological assessment of the effects of (R, S)-2-chloro-5-hydroxyphenylglycine (CHPG) on agonistic interactions in male mice

The manipulation of glutamate neurotransmission could represent a potential strategy for the pharmacotherapy of schizophrenic symptoms. Preclinical studies suggest that two subtypes of metabotropic glutamate (mGlu) receptors such as mGlu2/3 and mGlu5 receptors have the potential to ameliorate deficits in schizophrenia. In our study we evaluated the role of a non-specific mGlu receptor agonist ((1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid; 1S,3R-ACPD), mGlu5 receptor agonist or positive modulators ((RS)-2-Chloro-5-hydroxyphenylglycine;CHPG; [(3-Fluoro-phenyl)methylene]hydrazone-3-fluorobenzaldehyde; DFB; 3-Cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide; CDPPB) and a mGlu2/3 receptor agonist (2,2,2-Trifluoro-N-[4-(2-methoxyphenoxy)phenyl]-N-(3-pyrdinylmethyl)ethanesulfonamide hydrochloride; LY-487379) on performance in a cognitive task (Active Allothetic Place Avoidance) after sub-chronic administration of 5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclo-hepten-5,10-imine; MK-801 . The Active Allothetic Place Avoidance task is suitable for assessing the executive function and attention of animals and was previously validated for testing the effect of anti-psychotics. Application of the mGlu2/3 receptor agonist had no effect on cognitive impairment induced by MK-801. However, the mGlu5 receptor agonists ameliorated cognitive impairment induced by MK-801 without affecting locomotion. In conclusion, the mGlu5 receptor agonists could be effective in the treatment of cognitive deficits in patients with schizophrenia. However, the pro-cognitive effect of the agonist of mGlu2/3 receptors was not demonstrated in the present study.

Effect of co-application of Alpha1-Adrenergic antagonist and D2 antagonist on locomotion and behavior of rats in a place avoidance task

Study of a neurotransmitter substrate of spatial navigation is one of the most investigated topics in cognitive neurosciences. Active allothetic place avoidance (AAPA) task is a spatial behavioral paradigm allowing simultaneous assessment of changes in spatial behavior and locomotion of experimental animals. In the present study, we investigated the involvement of alpha1-adreneregic and dopamine D2 receptors in the locomotor activity and the spatial efficiency in the AAPA task. We administered specific receptor antagonists prazosin (1 and 2 mg/kg) and sulpiride (10 and 30 mg/kg) either separately, or co-applied them together. Results show that co-application of both drugs affects locomotion and behavior of rats at the doses, which cause minor or no impairments when injected independently. Such a potentiation of effect suggests that both types of receptors act synergistically to regulate the locomotion in the AAPA task. However future experiments are required to elucidate whether the behavioral deficit occurs as a result of decreased locomotion, or evolves as a stand - alone phenomenon. The presented experiments also support the usefulness of the AAPA task in the study of animal cognition.

Risperidone and ritanserin but not haloperidol block effect of dizocilpine on the active allothetic place avoidance task

Spatial working memory or short-term place memory is impaired in schizophrenia. The efficiency of antipsychotic drugs, particularly of typical antipsychotics, on cognitive deficit in schizophrenia remains disputable. Inhibition of serotonin (5-HT) 2A/2C receptors is important for cognitive improvement in schizophrenic patients treated with antipsychotics. The aim of the present work was to establish the effect of the 5-HT2A/2C receptor antagonist ritanserin (2.5 or 5 mg/kg), the dopamine D2 antagonist haloperidol (0.1 or 1 mg/kg), and the atypical antipsychotic risperidone (0.1 mg/kg or 1 mg/kg), which is an antagonist of both 5-HT2A/2C and D2 receptors, on cognitive deficit induced by subchronic administration of dizocilpine (MK-801, 0.1 mg/kg). We used the active allothetic place avoidance (AAPA) task, requiring the rat to differentiate between relevant and irrelevant stimuli, in a way similar to disruption of information processing disturbed in schizophrenic patients. Our results show that treatment with 5-HT2A/2C receptor antagonists, regardless of their effect on D2 receptors, blocked the cognitive impairment produced by MK-801. Haloperidol did not sufficiently reduce the deficit in AAPA induced by MK-801. Interestingly, administration of risperidone and haloperidol alone, but not ritanserin, impaired the AAPA performance in intact rats. Ritanserin and risperidone actually improve cognition independently of their effect on locomotor activity in an animal model of schizophrenia-like behavior. This finding is in accordance with the assumption that some antipsychotics are primarily effective against cognitive dysfunction in schizophrenia.

Role of alpha1- and alpha2-adrenoceptors in the regulation of locomotion and spatial behavior in the active place avoidance task: A dose–response study

Studies on the neurotransmitter substrate of locomotion and place navigation occupy a central position in behavioral neuroscience. Active allothetic place avoidance (AAPA) is a task, in which animals are trained to avoid a room frame defined stable sector on a continuously rotating arena. The aim of the present study was to test the effect of the blockage of alpha1- and alpha2-adrenoceptors, using specific antagonists prazosin and idazoxan, on the locomotor activity and spatial behavior in the AAPA task. Both prazosin and idazoxan at the highest doses (4 and 6 mg/kg, respectively) were found to decrease the locomotor activity in the AAPA and they also impaired navigational performance. The results suggest that antagonizing alpha-adrenoceptors with systemically administered drugs affects locomotor activity together with avoidance behavior and does not cause a purely cognitive deficit in the AAPA task.

Dopamine D2 receptors and alpha1-adrenoceptors synergistically modulate locomotion and behavior of rats in a place avoidance task

The processing of spatial information is the focus of interest for many cognitive neuroscientists. Approximately 10 years ago, a novel behavioral paradigm called active allothetic place avoidance (AAPA) was designed allowing the simultaneous assessment of locomotor and spatial behavior. The present study describes the effect of the combined treatment of Long-Evans rats with alpha1-adrenergic and D2 antagonists prazosin (1 mg/kg and 2 mg/kg) and sulpiride (10 mg/kg and 30 mg/kg) on locomotion and avoidance behavior in the AAPA task. Results show that co-application of both drugs leads to disturbances in locomotion and avoidance in rats at the doses, which caused no impairments when administered independently. This finding suggests that both types of receptors act synergistically to regulate locomotion and possibly spatial behavior.

Manipulation of D2 receptors with quinpirole and sulpiride affects locomotor activity before spatial behavior of rats in an active place avoidance task

Dopamine-mediated neurotransmission is widely studied with respect to motivation, motor activity and cognitive processes. The aim of the present study was to evaluate the role of D2 receptors in the behavior of rats in the active allothetic place avoidance (AAPA) task. D2 receptor agonist quinpirole and antagonist sulpiride were administered intraperitoneally 20 min prior to behavioral testing. Administration of quinpirole led to dose-dependent increase of locomotion; the spatial efficiency was spared across the dose range studied (0.05–1.0 mg/kg). In contrast, sulpiride decreased locomotor activity at a dose not influencing spatial efficiency (60 mg/kg); the highest dose of sulpiride (100 mg/kg) caused a deficit in both locomotor and spatial behaviors. The results suggest a relatively lesser importance of D2 receptors for spatial efficiency in the AAPA task, with a predominant influence of D2 receptor ligands on motor activity.

Active allothetic place avoidance task: evaluation of new and promising behavioral approach to testing spatial cognitive abilities of rodents.

Active allothetic place avoidance task: evaluation of new and promising behavioral approach to testing spatial cognitive abilities of rodents.

Further study of the effects of dopaminergic D1 drugs on place avoidance behavior using pretraining: Some negative evidence

Dopaminergic neurotransmission is considered to modulate cognitive processes, including spatial memory. The aim of this study was to further evaluate the role of the D1 receptor system in an active allothetic place avoidance (AAPA) task using pretrained rats. Our previous results showed enhanced AAPA learning after systemic injections of low doses of D1 agonist A77636, and the impairment of AAPA acquisition by D1 blocker SCH23390 [Stuchlik A, Vales K. Effect of dopamine D1 receptor antagonist SCH23390 and agonist A77636 on active allothetic place avoidance, a spatial cognition task. Behav Brain Res 2006;172(2):250–255]. In the present study, we used the intact-pretraining paradigm, in which animals were trained to the task prior to the injections and subsequently retrieval and reacquisition of AAPA while under the effects of the drugs was tested. Results showed that the intact pretraining partly eliminated the effects of A77636 and SCH23390 on AAPA performance, but a higher dose of SCH23390 caused a motor deficit in the retrieval session. We conclude that in the previous study, D1-active drugs may have had influence upon the non-spatial aspects of the AAPA.