Exploratory Behavior In Rats Research Articles

Effects of reward and punishment on exploratory behavior in rats

Effects of reward and punishment on exploratory behavior in rats

Hormonal and cognitive factors associated with the exploratory behavior of rats submitted to repeated sessions of the elevated plus-maze.

rats submitted to the elevated plus-maze (EPM) display a characteristic increase in open arm exploration and reduced risk assessment behaviors (RABs) after the administration of anxiolytic drugs. Upon re-exposure to the maze, however, the traditional measures of the EPM become resistant to these drugs. This intriguing phenomenon was initially observed for the benzodiazepine chlordiazepoxide and referred as one-trial tolerance (OTT). In this review, we summarized hormonal, cognitive and neuroanatomical data obtained from rats submitted to the test/retest protocol in the EPM. The re-exposure to the EPM is characterized by more prominent RABs and a distinct Fos protein distribution in the brain, particularly in limbic structures involved with the cognitive aspects of fear, such as the ventral regions of the medial prefrontal cortex (mPFC) and amygdala. Interestingly, naive rats treated with midazolam had a significant decrease in the number of Fos-positive neurons in the anterior cingulate cortex, area 1 (Cg1), anterior and dorsal premammillary nuclei of hypothalamus. On the other hand, midazolam caused a significant decrease in the number of Fos-positive neurons in the mPFC, amygdala, dorsomedial nucleus of hypothalamus and raphe nuclei in maze-experienced rats. Cg1 was the only structure targeted by the benzodiazepine in both sessions. Systemically administered midazolam before test or retest sessions reduced the RABs and plasma corticosterone levels in rats submitted to both sessions. Similar behavioral results were obtained with intra-Cg1 infusions of midazolam. The results reviewed here support the view of the crucial role of the RABs in the development of the OTT and point to this mPFC area as an important locus for the anxiolytic-like action of benzodiazepines in rodents. Keywords: elevated plus-maze, retest session, benzodiazepines, corticosterone, Fos expression, anterior cingulate cortex.

PKMζ inactivation induces spatial familiarity

Spatial familiarization consists of a decrease in the exploratory activity over time after exposure to a place. Here, we show that a 30-min exposure to an open field led to a pronounced decrease in the exploratory behavior of rats, generating context familiarity. This behavioral output is associated with a selective decrease in hippocampal PKMzeta levels. A short 5-min exposure did not induce spatial familiarity or a decrease in PKMzeta, while inactivation of hippocampal PKMzeta by the specific inhibitor ZIP was sufficient to induce spatial familiarity, suggesting that the decrease in PKMzeta is involved in setting a given context as a familiar place.

Exploratory Behavior in Rats Postnatally Exposed to Cocaine and Housed in an Enriched Environment

Exposure to cocaine in early periods of postnatal life is usually associated with changes in development of neurotransmitter systems and structure of the central nervous system. Such changes are most likely correlated with behavioral alterations. Environmental enrichment conditions (EC) in early stages is a factor that affects structural and behavioral development. The purpose of this study is to examine the effects of EC on rats postnatally exposed to cocaine on exploratory behavior. Wistar rats were assigned to four groups-Group 1: pups exposed to cocaine hydrochloride (15 mg/kg body weight/day) s.c., in two daily doses, from postnatal day (PND) 1 to 28 and reared in EC; Group 2: pups exposed to cocaine as previously described and reared in a standard environmental conditions (SC); Group 3: pups saline-injected and reared in EC; and Group 4: pups saline-injected and reared in SC. On PND 21, 24, and 28, groups of four rats (to reduce anxiety) were placed for 10 minutes into an arena with several objects. The following exploratory behavioral categories were examined: object interaction, exploration, manipulation, approximation, and total time of object contact. Animals from Group 2 showed decreased object interaction and total contact on PND 21. Control offspring reared in EE showed decreases in exploratory behavior at all ages analyzed compared with the control SE group, while cocaine-exposed animals reared in EC showed decreased object interaction, object approximation, and total exploratory behavior. The results in this group suggest that EC improved information acquisition and memory processes in animals postnatally exposed to cocaine.

Modification of the effects of 5-methoxy-N,N-dimethyltryptamine on exploratory behavior in rats by monoamine oxidase inhibitors

The hallucinogenic tea known as ayahuasca is made from a combination of psychoactive plants that contribute the active components N,N-dimethyltryptamine (DMT) and 5-methoxy-DMT (5-MeO-DMT), as well as the monoamine oxidase (MAO) inhibitors (MAOIs) harmine and harmaline for oral activity. The present study examined the effects of 5-MeO-DMT in combination with MAOIs in rats using the behavioral pattern monitor, which enables analyses of patterns of locomotor activity and exploration. Interaction studies using the serotonin (5-HT)(1A) antagonist WAY-100635 (1.0 mg/kg) and the 5-HT(2A) antagonist MDL 11,939 (1.0 mg/kg) were also performed to assess the respective contributions of these receptors to the behavioral effects of 5-MeO-DMT in MAOI-treated animals. 5-MeO-DMT (0.01, 0.1, and 1.0 mg/kg) decreased locomotor activity and investigatory behavior. In rats pretreated with a behaviorally inactive dose of harmaline (0.1 mg/kg), 1.0 mg/kg 5-MeO-DMT had biphasic effects on locomotor activity, initially reducing locomotion and then increasing activity as time progressed. The ability of harmaline to shift 5-MeO-DMT to a biphasic locomotor pattern was shared by the selective MAO(A) inhibitor clorgyline, whereas the selective MAO(B) inhibitor (-)-deprenyl was ineffective. The late hyperactivity induced by the combination of 1.0 mg/kg 5-MeO-DMT and 0.3 mg/kg clorgyline was blocked by pretreatment with MDL 11,939. Pretreatment with WAY-100635 failed to attenuate either the early hypoactivity or the late hyperactivity. The ability of harmaline to modify the behavioral effects of 5-MeO-DMT is mediated by the inhibition of MAO(A). Furthermore, 5-HT(2A) receptors are responsible for the late hyperactivity induced by 5-MeO-DMT in the presence of MAO(A) inhibitors.

The exploratory behaviour of rats in the hole-board apparatus: Is head-dipping a valid measure of neophilia?

The exploratory behaviour of laboratory rodents is of interest within a number of areas of behavioural pharmacology. However, how best to measure exploratory behaviour in rodents remains a contentious issue. Many unconditioned tests, such as the open field, potentially confound general locomotor activity with exploration. The hole-board apparatus appears to avoid this confound, as head-dipping into holes in the floor is assumed to be a valid measure of the subject's attraction towards novelty (neophilia). This study aimed to investigate whether head-dipping should be considered a valid measure of neophilia by comparing performance of adult male and female Lister hooded rats on the hole-board task (a) over repeated sessions and (b) when novel objects were absent or present underneath the holes. The results show that head-dipping initially decreased across repeated exposures, while time spent in the aversive central area increased. No change in head-dipping was seen in response to objects being placed underneath the holes. Rather than being a measure of neophilia, these results support the hypothesis that head-dipping represents an escape response, which declines as the subject becomes less fearful. These results are compared with previous studies of repeated exposure to other novel environments.

Thigmotactic responses in an open-field

The goal of the present study was to investigate the role of thigmotaxis (the tendency to remain close to vertical surfaces) in rat exploratory behavior in an open-field. Thigmotaxis was investigated in a parametric way, using 24 experimentally adult naive male Wistar rats (210-230 g). Exploratory behavior was studied in an open-field (N = 12) in 5-min sessions and behavior was analyzed in terms of where it occurred: in areas surrounded by two, one, or no walls. Another group of rats (N = 12) was studied in an open-field with blocks placed near two of the corners so as to make these corner areas surrounded by three walls. The floor of the open-fields was divided into 20-cm squares in order to locate the exact place of occurrence of each behavior. The following behaviors were recorded: entries into the squares, rearings, and groomings. In both types of open-field the rats chose to remain longer in the squares surrounded by the largest possible number of walls. In one of the open-fields, the mean time (seconds) spent in squares surrounded by two walls was longer than the time spent in squares surrounded by one or no walls (37.2, 7.7, and 1.8 s, respectively). In the other open-field, the mean time spent in squares surrounded by three walls was longer than the time spent in squares surrounded by two, one or no walls (41.7, 20.4, 7.0, and 2.6 s, respectively). Other measures presented a similar profile. These results indicate that rats are sensitive to the number of walls in an environment and prefer to remain close to them.

Preference for the light compartment of a light/dark cage does not affect rat exploratory behavior in the elevated plus-maze.

The are few reports on the relationship between elevated plus-maze and effects of maintenance conditions in the days prior to the test. Previously, we have demonstrated that being forcibly in total dark or in light for four days does not alter exploratory behavior in the plus-maze. The present study aimed at recording illumination level preferences in rats using a box with light and dark compartments (or another with two light compartments) and the behavioral effect of this choice on the plus-maze. The rats allowed to express their preference to remain in one particular level of illumination tended to stay initially in the dark compartment and gradually preferred to remain in the light compartment. When tested in the elevated plus-maze there were no effects in comparison to controls kept in commercial cages.

Recruiting Extrasynaptic NMDA Receptors Augments Synaptic Signaling

N-Methyl-d-aspartate receptor (NMDAR) activation may promote cell survival or initiate cell death, with the outcome dependent on whether synaptic or extrasynaptic receptors are activated. Similarly, this differential activation has been proposed to govern the direction of plasticity. However, the physiological parameters necessary to activate extrasynaptic NMDARs in brain slices remain unknown. Using the irreversible use-dependent NMDAR antagonist MK-801 to isolate extrasynaptic NMDARs, we have tested the ability of short-stimulation trains from 5 to 400 Hz to activate these receptors on CA1 hippocampal slice pyramidal neurons. Frequencies as low as 25 Hz engage extrasynaptic NMDARs, with maximal activation at frequencies between 100 and 200 Hz. Since similar bursts of synaptic input occur during exploratory behavior in rats, our results demonstrate that "extrasynaptic" NMDARs regularly participate in synaptic transmission. Further, 175-Hz-stimulation trains activate all available synaptic and extrasynaptic dendritic NMDARs, suggesting these NMDARs act as synaptic receptors as needed, transiently increasing synaptic strength. Thus extrasynaptic NMDARs play a vital role in synaptic physiology, calling into question their status as "extrasynaptic."

Multivariate analysis of the modifications induced by an environmental acoustic cue on rat exploratory behavior

The aim of the present paper is to study by means of a multivariate analysis the modifications induced by an environmental acoustic cue on the structure of rat exploratory behavior. Adult male Wistar rats were observed during the exploration of a soundproof observation box. Each rat was acoustically stimulated after 150 s from the beginning of the experimental session, lasting 300 s, and recorded through a digital videocamera. A frame by frame analysis was thereafter carried out using a professional video-recording system. Thirteen behavioral patterns were selected: immobility, immobile-sniffing, walking, rearing, climbing, chewing, paw-licking, face-grooming, body-grooming, head-turning, tuning, oriented-sniffing, focusing. Both descriptive and multivariate analyses (cluster, stochastic, adjusted residuals) were carried out. Through descriptive statistical analysis, latencies and per cent distribution of each pattern were studied. A multivariate cluster analysis revealed the presence of three main behavioral clusters, an additional one being identified following acoustic stimulation. Multivariate stochastic analysis showed that all the patterns converged on immobile-sniffing which could represent a key component in behavioral switching processes related to environmental exploration. Moreover, through adjusted residuals, the degree of relationship among different patterns was shown according to statistic Z-distribution. Our data assign new ethological meanings to different behavioral patterns. Notably, head-turning is suggested to be considered as a generic directional search and tuning as a subtle activity of stimulus localization.

How do global and local geometries shape exploratory behavior in rats?

The present study examines how rats process object information in relation to other objects as well as to the global shape of an enclosure. Rats were introduced into either a round or a square arena with various arrays of freestanding portable corners (objects) that differed in spacing, orientation, and number. We found that the time spent at the objects was substantially higher in the round compared with the square arena. Rats in the square arena distributed their time evenly between arena perimeter and objects; however, they visited the objects more frequently than the perimeter. Rats tested in either round or square arena favored staying at the interior of the object regardless of its orientation in the arena. Finally, only geometric changes in the object array affected the rats’ level of activity. These findings demonstrate that the rats were able to detect the geometry of the enclosure, the array, and the objects. We suggest that the context of the global enclosure geometry affects the meaning of landmarks (objects) for the observer, which in turn results in a different distribution of activity. Specifically, an object's local geometry served mainly in the context of a safe place in the round arena, as manifested in extended duration of stay at the objects, however in the square arena served mainly as a place of interest, as manifested in the frequent visits, but without their staying there. Thus, the geometries of the enclosure, the object array, and the discrete objects, together shape exploratory behavior in rats.

A model for the rat exploratory behavior in the elevated plus-maze

A model for the rat exploratory behavior in the elevated plus-maze

The point of entry contributes to the organization of exploratory behavior of rats on an open field: An example of spontaneous episodic memory

The exploratory behavior of rats on an open field is organized in that animals spend disproportionate amounts of time at certain locations, termed home bases, which serve as centers for excursions. Although home bases are preferentially formed near distinctive cues, including visual cues, animals also visit and pause and move slowly, or linger, at many other locations in a test environment. In order to further examine the organization of exploratory behavior, the present study examined the influence of the point of entry on animals placed on an open field table that was illuminated either by room light or infrared light (a wavelength in which they cannot see) and near which, or on which, distinctive cues were placed. The main findings were that in both room light and infrared light tests, rats visited and lingered at the point of entry significantly more often than comparative control locations. Although the rats also visited and lingered in the vicinity of salient visual cues, the point of entry still remained a focus of visits. Finally, the preference for the point of entry increased as a function of salience of the cues marking that location. That the point of entry influences the organization of exploratory behavior is discussed in relation to the idea that the exploratory behavior of the rat is directed toward optimizing security as well as forming a spatial representation of the environment.

Screen for genes in periaqueductal grey of male Wistar rats related to reduced exploratory activity in the elevated plus-maze

Aim of a present study was to find genes in the periaqueductal grey (PAG) related to the exploratory behavior in rats. Male Wistar rats were divided according to their exploratory behavior in the elevated plus-maze model of anxiety into two groups: high (non-anxious) and low (anxious) exploratory activity. Differential expression of genes was analyzed using the cDNA representational difference analysis (RDA). Q-RT-PCR was used to confirm most prominent changes and functional annotation of the identified genes was performed to establish pathways related to exploratory behavior of rats. We found different genetic activation related to the exploratory activity of rats. Rats with low exploratory activity showed increase in the intracellular signal transduction and in GABA, vasopressin and adrenergic receptor activities. Functional annotation confirmed significant induction of cAMP system and GTPases in rats with anxious-type behavior. On the other hand, rats with high exploratory activity in the elevated plus-maze (non-anxious type of behavior) had increased activity of genes forming “behavioral fear response” system. These changes were specific to PAG, because they were not found in the cerebellum. In addition, plasma corticosterone levels were significantly higher in rats with non-anxious behavior compared to anxious behavior. Our results show that non-anxious behavior is related to activation of “fear response system” and more intense activation of HPA axis. Possibly it means that this system helps animals to cope with the threatening circumstances. More detailed analysis of this potential “fear response system” is necessary in the further studies for understanding its role in the regulation of emotional behavior.

The effects of acute and chronic administration of corticosterone on rat behavior in two models of fear responses, plasma corticosterone concentration, and c-Fos expression in the brain structures

The aim of this paper was to examine changes in rat emotional behavior, and to find the brain structures, which are involved in the mediation of behavioral effects, related to the repeated administration of glucocorticoids. The effects of acute and chronic pretreatment of rats with two doses of corticosterone (5 and 20 mg/kg) were analyzed in two models of fear responses: neophobia-like behavior in the open field test, and freezing reaction in the conditioned fear test. Behavioral effects of repeated glucocorticoid administration were compared to changes in blood total corticosterone concentration, and expression of immediate early gene (c-Fos) in brain structures. It was found that acute administration of corticosterone (90 min before tests) enhanced rat exploratory behavior, and decreased freezing reaction. On the other hand, repeated administration of corticosterone (for 25 days, the final injection 90 min before contextual fear conditioning training) decreased plasma corticosterone concentration, inhibited exploratory behavior, enhanced freezing responses on retest and produced a complex pattern of changes in c-Fos expression, stimulated by exposure of rats to the aversively conditioned context. Aversive context induced c-Fos in the magnocellular neurons of the hypothalamic paraventricular nucleus (mPVN), dentate gyrus (DG), cingulate cortex area 1 (Cg1), and primary motor cortex (M1). In rats chronically treated with corticosterone this effect was attenuated in the mPVN and DG, enhanced in the M1, and additionally observed in the CA1, CA2 layers of the hippocampus, and in the central nucleus of amygdala (CeA), in comparison to control animals not subjected to contextual fear test. In sum, the present data suggest that chronic corticosterone treatment enhances the activity of primary motor cortex and CeA with subsequent improvement of memory of aversive events, and simultaneously stimulates a negative feedback mechanism operating in PVN with ensuing decrease in blood corticosterone concentration.

The exploratory behavior of rats in an open environment optimizes security

When given a locomotor/exploratory test in the laboratory, rats form one or more home bases, operationally defined as places where they spend a disproportionate period of their time and from which they make excursions. Because exploratory tests in the laboratory necessarily restrict the animals’ movements, the cause of exploration (e.g., fear, curiosity, innate disposition) and the extent to which organization is imposed by the restriction of the testing environment has not been fully examined. In the present study, rats received exploratory tests in environments in which restrictions were remote; in a parking lot or on a playing field. Each rat began a test in one of three conditions: in a small refuge, within a transparent open home cage, or beside a landmark. In the parking lot, the rats failed to leave the small refuge, made excursions from the home cage, and left the landmark, usually at a gallop, and made no movements of returning. On the playing field they remained in the small refuge, left and returned to the open home cage, and were more likely to permanently leave the landmark at a gallop. Rats that displayed a strong preference for the landmark over three test sessions in a laboratory, also immediately left the same landmark when tested on the playing field. The pattern of behavior, in which the rats failed to explore from a secure starting position and were increasingly likely to run away as security decreased, suggests that a primary function of locomotor behavior in a novel environment is to optimize security. The results are discussed in relation to the advantages of investigating the influence of neural processes on exploration in terms optimization theory versus motivational theory.

Midazolam inhibits neophobia-induced Fos expression in the rat hippocampus

The effect of midazolam on expression of c-Fos protein was examined in the rat hippocampus, following the open field test of neophobia. It was found that pretreatment of rats with midazolam, at the dose of 0.5 mg/kg, enhanced rat exploratory behavior, and inhibited neophobia related stimulation of c-Fos in the CA-1 and CA-3 areas of the hippocampus. The presented results provide new immunocytochemical data on the involvement of hippocampus in emotional processes related to neophobia, and indicate a possible site of action of benzodiazepines.

Effect of different illumination levels on rat behavior in the elevated plus-maze

The present study addressed the role of environmental light intensity on the exploratory behavior of rats in the elevated plus-maze, with the specific goal of determining the light intensity threshold for triggering the aversion to the open arms. Male Wistar-derived rats were tested in the elevated plus-maze under different illumination levels: 0, 1, 3, 10, 30, 100 and 300 lx. Exploratory behavior occurring in the open arms (e.g., entries and time spent in these arms) was more intense under 0 and 1 lx than under the other illumination levels, which did not differ among themselves; on the other hand, locomotor behavior (as indicated by frequency of entries and distance run in the closed arms) was not altered under all illumination conditions. The data indicated that vision is important in triggering aversion to the open arms of the elevated plus-maze. They also indicated that the threshold of such aversion was found between 1 and 3 lx environmental illumination and that the phenomena is not intensity-dependent but rather of an all-or-none type. It should be emphasized that these conclusions only stand for unfamiliar environments. The role of light in familiar environments is currently under investigation in our laboratory.

Effect of CCK1 and CCK2 receptor blockade on amphetamine-stimulated exploratory behavior and sensitization to amphetamine

Interactions between dopaminergic neurotransmission and cholecystokinin (CCK) in the CNS may be important in the pathogenesis of psychotic disorders and substance abuse. In this study, the effect of coadministration of the selective CCK receptor antagonists devazepide and L-365,260 (for selectively blocking CCK1 and CCK2 receptors, respectively), on the effect of amphetamine on the rat exploratory behavior, and on sensitization of locomotor response to amphetamine, were studied. Amphetamine (0.5 mg/kg) increased exploratory activity in the exploration box for 5 consecutive testing days, while devazepide (10 μg/kg) blocked and L-365,260 (10 μg/kg) enhanced amphetamine-induced stimulation of activity. Devazepide coadministration prevented the development of sensitization to amphetamine, while coadministration of L-365,260 with amphetamine potentiated the locomotor effect of a challenge dose of amphetamine. These results suggest that endogenous CCK, released during exploratory activity, shapes behavioral responses to amphetamine by acting on both receptor subtypes, and modulates the development of sensitization to amphetamine.

Responses of dorsal subicular neurons of rats during object exploration in an extended environment.

The subiculum receives a direct projection from the perirhinal cortex, a cortical area whose neurons are responsive to the novelty or familiarity of objects encountered in the environment. We made recordings of subicular neuronal activity while male adult Wistar rats conducted object exploration tasks, which have been previously shown to cause changes in the exploratory behaviour of rats and which are dependent upon the integrity of structures within the hippocampal formation. In the current study, the exploratory behaviour of the rats was also modified in a manner consistent with them perceiving the novelty and familiarity of the objects used as part of the apparatus. Subicular cell firing, however, appeared to correlate best not with object novelty or familiarity, but with the concurrent location and speed of the rats within the task environment. These findings are discussed in light of previously reported 'object-responsive' subicular firing correlates.