Most cited article - PubMed ID 11040412
Passive and active place avoidance as a tool of spatial memory research in rats
The active place avoidance task is a dry-arena task used to assess spatial navigation and memory in rodents. In this task, a subject is put on a rotating circular arena and avoids an invisible sector that is stable in relation to the room. Rotation of the arena means that the subject's avoidance must be active, otherwise the subject will be moved in the to-be-avoided sector by the rotation of the arena and a slight electric shock will be administered. The present experiment explored the effect of variable arena rotation speed on the ability to avoid the to-be-avoided sector. Subjects in a group with variable arena rotation speed learned to avoid the sector with the same speed and attained the same avoidance ability as rats in a group with a stable arena rotation speed. Only a slight difference in preferred position within the room was found between the two groups. No difference was found between the two groups in the dark phase, where subjects could not use orientation cues in the room. Only one rat was able to learn the avoidance of the to-be-avoided sector in this phase. The results of the experiment suggest that idiothetic orientation and interval timing are not crucial for learning avoidance of the to-be-avoided sector. However, idiothetic orientation might be sufficient for avoiding the sector in the dark.
- Keywords
- Inertial idiothetic navigation, Interval timing, Rats, Spatial navigation, Substratal idiothetic navigation,
- Publication type
- Journal Article MeSH
The involvement of the serotonin system in the pathophysiology of schizophrenia has been elucidated by experiments with hallucinogens. Application of a hallucinogen to humans leads to changes in perception, cognition, emotions, and induction of psychotic-like symptoms that resemble symptoms of schizophrenia. In rodent studies, their acute administration affects sensorimotor gating, locomotor activity, social behavior, and cognition including working memory, the phenotypes are considered as an animal model of schizophrenia. The complexity and singularity of human cognition raises questions about the validity of animal models utilizing agonists of 5-HT2A receptors. The present study thus investigated the effect of psilocin on memory acquisition, reinforced retrieval, and memory consolidation in rats. Psilocin is a main metabolite of psilocybin acting as an agonist at 5-HT2A receptors with a contribution of 5-HT2C and 5-HT1A receptors. First, we tested the effect of psilocin on the acquisition of a Carousel maze, a spatial task requiring navigation using distal cues, attention, and cognitive coordination. Psilocin significantly impaired the acquisition of the Carousel maze at both doses (1 and 4 mg/kg). The higher dose of psilocin blocked the learning processes even in an additional session when the rats received only saline. Next, we examined the effect of psilocin on reinforced retrieval and consolidation in the Morris water maze (MWM). The dose of 4 mg/kg disrupted reinforced retrieval in the MWM. However, the application of a lower dose was without any significant effect. Finally, neither the low nor high dose of psilocin injected post-training caused a deficit in memory consolidation in the MWM. Taken together, the psilocin dose dependently impaired the acquisition of the Carousel maze and reinforced retrieval in MWM; however, it had no effect on memory consolidation.
- Keywords
- Carousel maze, Morris water maze, allocentric navigation, hallucinogenic alkaloids, learning, memory, psilocin, spatial memory,
- Publication type
- Journal Article MeSH
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.
- MeSH
- Time Factors MeSH
- Behavior, Animal drug effects MeSH
- Dizocilpine Maleate pharmacology MeSH
- Haloperidol pharmacology MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Risperidone pharmacology MeSH
- Ritanserin pharmacology MeSH
- Avoidance Learning drug effects MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Dizocilpine Maleate MeSH
- Haloperidol MeSH
- Risperidone MeSH
- Ritanserin MeSH
Hippocampal activity is thought to encode spatial representations in a distributed associative network. This idea predicts that partial hippocampal lesions would spare acquisition and impair retrieval of a place response as long as enough connections remained intact to encode associations. Water maze experiments supported the predictions, but the prediction of impaired retrieval was not supported when tetrodotoxin (TTX) was injected into one hippocampus and rats were tested in a place avoidance task on a rotating arena with shallow water. The rotation dissociated relevant distal stimuli from irrelevant self-motion stimuli. To explain the discrepancy, we hypothesized that the segregation of relevant and irrelevant stimuli and stimuli association into representations are distinct hippocampus-dependent operations, and whereas associative representation is more sensitive to disruption during retrieval than learning, stimulus segregation is more sensitive to disruption during learning than during retrieval. The following predictions were tested: (1) the TTX injection would spare learning but (2) impair retrieval of a place response in the water maze, which has a high associative representational demand but a low demand for segregation; (3) the injection would impair learning but (4) spare retrieval of place avoidance in the rotating arena filled with water, which has a high demand for stimulus segregation but a low associative representational demand. All four predictions were confirmed. The hypothesis also explains the pattern of sparing and impairment after the TTX injection in other place avoidance task variants, leading us to conclude that stimulus separation and association representation are dissociable functions of the hippocampus.
- MeSH
- Analysis of Variance MeSH
- Anesthetics, Local toxicity MeSH
- Maze Learning drug effects physiology MeSH
- Time Factors MeSH
- Behavior, Animal MeSH
- Hippocampus drug effects injuries physiology MeSH
- Rats MeSH
- Memory Disorders chemically induced physiopathology MeSH
- Rats, Long-Evans MeSH
- Mental Recall drug effects physiology MeSH
- Tetrodotoxin toxicity MeSH
- Avoidance Learning drug effects physiology MeSH
- Escape Reaction drug effects physiology MeSH
- Space Perception drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Anesthetics, Local MeSH
- Tetrodotoxin MeSH
The present study describes a task testing the ability of rats to trigger operant behavior by their relative spatial position to inaccessible rotating objects. Rats were placed in a Skinner box with a transparent front wall through which they could observe one or two adjacent objects fixed on a slowly rotating arena (d = 1 m) surrounded by an immobile black cylinder. The direction of arena rotation was alternated at a sequence of different time intervals. Rats were reinforced for the first bar-press that was emitted when a radius separating the two adjacent objects or dividing a single object into two halves (pointing radius) entered a 60 degrees sector of its circular trajectory defined with respect to the stationary Skinner box (reward sector). Well trained rats emitted 62.1 +/- 3.6% of responses in a 60 degrees sector preceding the reward sector and in the first 30 degrees of the reward sector. Response rate increased only when the pointing radius was approaching the reward sector, regardless of the time elapsed from the last reward. In the extinction session, when no reward was delivered, rats responded during the whole passage of the pointing radius through the former reward sector and spontaneously decreased responding after the pointing radius left this area. This finding suggests that rats perceived the reward sector as a continuous single region. The same results were obtained when the Skinner box with the rat was orbiting around the immobile scene. It is concluded that rats can recognize and anticipate their position relative to movable objects.
- MeSH
- Behavior, Animal * MeSH
- Rats MeSH
- Reward MeSH
- Conditioning, Operant * MeSH
- Rats, Long-Evans MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH