Most cited article - PubMed ID 9705006
Rodent navigation after dissociation of the allocentric and idiothetic representations of space
Chronic sensitization to serotonin 1A and 7 receptors agonist 8-OH-DPAT induces compulsive checking and perseverative behavior. As such, it has been used to model obsessive-compulsive disorder (OCD)-like behavior in mice and rats. In this study, we tested spatial learning in the 8-OH-DPAT model of OCD and the effect of co-administration of memantine and riluzole-glutamate-modulating agents that have been shown to be effective in several clinical trials. Rats were tested in the active place avoidance task in the Carousel maze, where they learned to avoid the visually imperceptible shock sector. All rats were subcutaneously injected with 8-OH-DPAT (0.25 mg/kg) or saline (control group) during habituation. During acquisition, they were pretreated with riluzole (1 mg/kg), memantine (1 mg/kg), or saline solution 30 min before each session and injected with 8-OH-DPAT ("OH" groups) or saline ("saline" groups) right before the experiment. We found that repeated application of 8-OH-DPAT during both habituation and acquisition significantly increased locomotion, but it impaired the ability to avoid the shock sector. However, the application of 8-OH-DPAT in habituation had no impact on the learning process if discontinued in acquisition. Similarly, memantine and riluzole did not affect the measured parameters in the "saline" groups, but in the "OH" groups, they significantly increased locomotion. In addition, riluzole increased the number of entrances and decreased the maximum time avoided of the shock sector. We conclude that monotherapy with glutamate-modulating agents does not reduce but exacerbates cognitive symptoms in the animal model of OCD.
- Keywords
- 8-OH-DPAT, memantine, memory, obsessive-compulsive disorder, riluzole, spatial learning,
- MeSH
- 8-Hydroxy-2-(di-n-propylamino)tetralin adverse effects pharmacology MeSH
- Behavior, Animal drug effects MeSH
- Rats MeSH
- Memantine pharmacology MeSH
- Disease Models, Animal MeSH
- Obsessive-Compulsive Disorder * chemically induced drug therapy physiopathology MeSH
- Memory drug effects MeSH
- Rats, Long-Evans MeSH
- Spatial Learning drug effects MeSH
- Riluzole pharmacology 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
- 8-Hydroxy-2-(di-n-propylamino)tetralin MeSH
- Memantine MeSH
- Riluzole MeSH
Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks. However, many of these results may be potentially confounded by disruptions of functions other than spatial learning and memory. Although studies with selective antimuscarinics point to mutually opposite effects of M1 and M2 receptors, their particular contribution to spatial cognition is still poorly understood, partly due to a lack of truly selective agents. Furthermore, constitutive knock-outs do not always support results from selective antagonists. For modeling impaired spatial cognition, the scopolamine-induced amnesia model still maintains some limited validity, but there is an apparent need for more targeted approaches such as local intracerebral administration of antagonists, as well as novel techniques such as optogenetics focused on cholinergic neurons and chemogenetics aimed at cells expressing metabotropic mAChRs.
- Keywords
- acetylcholine, behavior, biperiden, learning, memory, receptor, rodents, scopolamine,
- Publication type
- Journal Article MeSH
- Review MeSH
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 spatial orientation of vertebrates is implemented by two complementary mechanisms: allothesis, processing the information about spatial relationships between the animal and perceptible landmarks, and idiothesis, processing the substratal and inertial information produced by the animal's active or passive movement through the environment. Both systems allow the animal to compute its position with respect to perceptible landmarks and to the already traversed portion of the path. In the present study, we examined the properties of substratal idiothesis deprived of relevant exteroceptive information. Rats searching for food pellets in an arena formed by a movable inner disk and a peripheral immobile belt were trained in darkness to avoid a 60 degrees sector; rats that entered this sector received a mild foot shock. The punished sector was defined in the substratal idiothetic frame, and the rats had to determine the location of the shock sector with the use of substratal idiothesis only, because all putative intramaze cues were made irrelevant by angular displacements of the disk relative to the belt. Striking impairment of place avoidance by this "shuffling procedure" indicates that effective substratal idiothesis must be updated by exteroceptive intramaze cues.
Spatial memory of animals is usually tested in navigation tasks that do not allow recognition and recall processes to be separated from the mechanisms of goal-directed locomotion. In the present study, place recognition was examined in rats (n = 7) confined in an operant chamber mounted on the periphery of a slowly rotating disk (diameter 1 m, angular velocity 9 degrees /s). The animals were passively transported over a circular trajectory and were rewarded for bar pressing when they passed across a 60 degrees -wide segment of the path. This segment was recognizable with reference to room landmarks visible from the operant box. Responding defined in the coordinate system of the room increased when the chamber entered the 60 degrees -wide approach zone, culminated at the entrance into the reward sector, was decreased inside it by eating the available reward, and rapidly declined to zero at the exit from this zone. When reward was discontinued, the skewed response distribution changed into a symmetric one with a maximum in the center of the reward sector. With advancing extinction, the response peak in the reward sector decreased in most rats proportionally to the overall decline of bar pressing. The rewarded and nonrewarded response patterns indicate that passively transported rats can recognize their position in the environment with an accuracy comparable to that of actively navigating animals and that location-driven operant responding can serve as a useful tool in the analysis of the underlying neural mechanisms.
- MeSH
- Behavior, Animal physiology MeSH
- Rats MeSH
- Orientation physiology MeSH
- Rats, Long-Evans MeSH
- Food Deprivation MeSH
- Spatial Behavior physiology MeSH
- Rotation * MeSH
- Pattern Recognition, Visual physiology MeSH
- Learning physiology MeSH
- Environment Design MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Foraging rats learned to avoid footshock that was present in a part of a circular arena that was either stable or rotating slowly in a lighted room. The rotation dissociated spatial information in the separate reference frames of the room and arena. After learning to avoid the shocked region in either condition, in the absence of shock, memory for this place was expressed by simultaneous avoidance of an area defined in the reference frame of the room as well as of an area defined in the reference frame of the rotating arena. Spatial memories in these distinct reference frames were acquired, retrieved, and extinguished autonomously.
- MeSH
- Time Factors MeSH
- Behavior, Animal physiology MeSH
- Rats, Inbred Strains MeSH
- Rats MeSH
- Memory physiology MeSH
- Spatial Behavior physiology MeSH
- Light MeSH
- Avoidance Learning MeSH
- Visual Perception MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
