Postsurgical enrichment aids adult hemidecorticate rats on a spatial navigation task

The effect of environmental enrichment on normal rats, rats that received hemidecortication at birth, and rats that received hemidecortication when adult was studied in the Morris water task, which is a spatial navigation task requiring the use of distal cues for successful performance. Enrichment was achieved by housing the rats for 90 days in a large outdoor compound that was designed to model a natural environment. Adult hemidecorticated lab-raised rats were severely impaired in the acquisition of the task but neonatally hemidecorticated rats, although also impaired, showed significant sparing. Postsurgical, but not presurgical, enrichment of adult hemidecorticated rats significantly enhanced their recovery. Enrichment had little effect on neonatally decorticated rats or on normal rats. Although there were no gross anatomical changes associated with enrichment, the paradigm provides both a robust phenomena and a cortically dependent task that is ideal for investigating the processes in the remaining intact hemisphere that must support recovery.     

The significance of crossed and uncrossed projections for the acquisition and retrieval of visual engrams in hooded and albino rats

Summary Occlusion of one eye and functional hemidecortication by cortical spreading depression (CSD) were used to examine the relative importance of crossed and uncrossed visual projections for pattern discrimination learning in hooded and albino rats. Whereas functionally hemidecorticate albino rats were unable to learn in 200 trials a horizontal-vertical discrimination when using the eye contralateral to the depressed hemisphere, hooded rats needed under similar conditions three times as many trials to criterion (167) than when using opposite eye and hemisphere (59). An engram established in intact animals with both eyes could be retrieved in functionally hemidecorticate rats of both strains even with the eye ipsilateral to the intact hemicortex, but retraining required about twice as many trials as when using the contralateral eye. Retrieval of monocularly acquired engrams was less efficient under similar conditions. Pattern discrimination formed through crossed or uncrossed visual projections during monocular occlusion and contralateral or ipsilateral CSD was completely lateralized, since relearning with naive eye and hemisphere proceeded at the same rate as the original learning. On the contrary, a black-white discrimination trained with the eye contralateral to the depressed hemisphere could be partly retrieved by the untrained eye and hemisphere. It is concluded that the ipsilateral visual projection is more effective in hooded than in albino rats and that it can be more efficiently used for retrieval than for acquisition.This research was partly supported by the Foundations' Fund for Research in Psychiatry, Grant G69-453.     

Enrichment versus exercise effects on motor impairments following cortical removals in rats

Groups of rats were exposed to an enriched environment, given access to an activity wheel, or individually housed in wire mesh cages, impoverished. Rats were exposed in groups of four to the enriched environment or placed individually in the activity wheel for 2 h per day for 25 days preoperatively. Within each exposure group, rats sustained bilateral removals of sensorimotor cortex, or were sham-operated controls. Animals were trained preoperatively to locomote across a narrow elevated runway. Postoperatively, locomotor testing was initiated 17 days after surgery throughout which time all animals were maintained under impoverished conditions. Locomotor deficits following cortical damage were a function of preoperative exposure: enriched rats were least impaired; impoverished rats were most impaired. Rats allowed running wheel activity initially showed the same marked deficits as impoverished animals but recovered more rapidly. The opportunity for physical exercise afforded wheel animals preoperatively may have enhanced motor capabilities that aided recovery. However, physical activity alone did not yield the same protective effects from initial impairment as enrichment. Greater elaboration of neural structures associated with perceptual-motor enrichment probably accounted for the initial sparing of the enriched group.     

Behavioral variability in SHR and WKY rats as a function of rearing environment and reinforcement contingency.

The spontaneously hypertensive rat (SHR) may model aspects of human attention deficit hyperactivity disorder (ADHD). For example, just as responses by children with ADHD tend to be variable, so too SHRs often respond more variably than do Wistar-Kyoto (WKY) control rats. The present study asked whether behavioral variability in the SHR strain is influenced by rearing environment, a question related to hypotheses concerning the etiology of human ADHD. Some rats from each strain were reared in an enriched environment (housed socially), and others were reared in an impoverished environment (housed in isolation). Four groups--enriched SHR, impoverished SHR, enriched WKY, and impoverished WKY--were studied under two reinforcement contingencies, one in which reinforcement was independent of response variability and the other in which reinforcement depended upon high variability. The main finding was that rearing environment did not influence response variability (enriched and impoverished subjects responded similarly throughout). However, rearing environment affected body weight (enriched subjects weighted more than impoverished subjects) and response rate (impoverished subjects generally responded faster than enriched subjects). In addition, SHRs tended to respond variably throughout the experiment, whereas WKYs were more sensitive to the variability contingencies. Thus, behavioral variability was affected by genetic strain and by reinforcement contingency but not by the environment in which the subjects were reared.     

The effect of conspecifics on corticoadrenal response of rats to a novel environment

The effect of housing conditions and the presence of a conspecific on corticoadrenal response to a novel environment was studied in male Sprague-Dawley rats. The response to a novel environment was the same in rats housed in groups and rats housed alone for 20 days before testing, suggesting that isolation during adulthood did not affect corticoadrenal response to a novel environment. The presence of a nonfamiliar rat (proceeding from another home cage) did not modify corticoadrenal response to the novel environment but the presence of a rat proceeding from the same home cage induced a higher corticoadrenal response to this stressful stimuli. These results can be explained considering that rats exhibit greater emotional reactivity, as measured by adrenal function, in situations which combine familiar (the other rat) and novel (the box) elements than those completely unfamiliar.     

The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry

To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long-Evans rats sustaining a serotonin depletion (150 microg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: -23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC.     

Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment

The effects of aging and of housing in an enriched environment on performance in an 8-arm radial maze were evaluated in young adult (7-8 months) and old (30-33 months) male Brown-Norway rats, using a procedure in which the rats were confined for 8 s to the central platform of the maze between consecutive choices. Although the old rats attained a level of performance which was clearly above change, they were shown to perform worse than the young rats. No performance differences were found between differentially housed rats of the same age group. In a second experiment recovery cycles of visual evoked potentials were determined in the same rats by using paired flashes with an interstimulus time of 400, 300, 200, or 100 ms. Recovery was consistently smaller in the old rats as compared to the young ones. No correlation could be demonstrated, however, between radial maze performance or housing condition and recovery functions of the visual evoked potentials. This finding indicates that a decline in visual sensitivity cannot readily explain the impaired radial maze performance of old rats. Evidence which suggests that age-related hippocampal changes play a major role in the radial maze performance deficit is discussed.     

Stress and emotional memory: a matter of timing

Stressful events activate the amygdala and a network of associated brain regions. Studies in both humans and rodents indicate that noradrenaline has a prominent role in this activation. Noradrenaline induces a hypervigilant state that helps to remember the event. This mnemonic effect is enhanced when the situation is so stressful that substantial amounts of corticosteroids are released and reach the amygdala. The combination of the two hormones leads to optimal strengthening of contacts and thus memory. Yet, rises in corticosteroid levels that are not precisely synchronized with noradrenaline release do not act synergistically but rather prevent or suppress the effect of noradrenaline. This dynamic interaction illustrates the adaptive and potentially protective capacity of corticosteroids regarding traumatic memories.     

Effects of ethanol withdrawal on muricidal behavior

When naive rats of our colony were individually housed for 1 month with free access to laboratory chow and water as drinking fluid, 6% exhibited muricidal behavior. When naive rats of the same colony were similarly housed but received ethanol 20% in water as the sole source of drinking fluid (ll.5 g ethanol/kg/day), the percentage of killer rats was the same. However, when the rats were housed in similar conditions and submitted to a 1-day ethanol withdrawal, the percentage of muricidal rats increased to 25%. Ethanol intake in the same conditions as described above did not change muricidal behavior of spontaneous killers and did not induce killing behavior in nonkiller animals. GABA-mimetic agents administered IP blocked ethanol withdrawal-induced killing behavior as well as spontaneous muricidal activity.     

Effect of postweaning social experience on response of Siberian hamsters (Phodopus sungorus sungorus) toward young

Between 18 and 50 days of age, Siberian hamsters were housed either with same-sex littermates, opposite-sex littermates, opposite-sex littermates and parents, or opposite-sex littermates, parents, and a younger litter. When adults, these animals were presented with two 3-8-day-old pups for 8 hr, and their responses were recorded. Rearing conditions did not affect behavior of females. Males housed with female littermates in the absence of a younger litter showed fewer pup attacks and more nesting with pups than did males housed only with other males. Thus, housing with females in the early postweaning period may influence males' later (adult) responses toward pups. Only among hamsters housed with same-sex littermates did males and females differ in their response to pups, a result emphasizing that sex differences in behavior may depend on early social rearing.     

Social mediation of puberty: an adaptive female strategy?

Females of two hamster species with contrasting degrees of gregariousness were tested for social influences on the timing of sexual maturation. When female dwarf hamsters (Phodopus sungorus campbelli), a gregarious species, were housed with an adult male at weaning, they began estrous cycles significantly earlier than when they were housed alone or with their family. Females housed with one or two female siblings at weaning matured significantly later than did all other females. Once mature, females housed with familiar males conceived later than did females housed with unfamiliar males. Rearing conditions also affected body weight; those housed with female siblings grew more slowly and attained a lower weight at 8 weeks of age than did females in all other groups. In contrast, when weanling female golden hamsters (Mesocricetus auratus), a solitary species, were housed with either an adult male, two female siblings, or alone, they did not differ in their rate of sexual maturation or growth. It is suggested that the degree to which social factors can accelerate or delay puberty is an adaptive characteristic and may be correlated with the degree of gregariousness of a species.     

Signalled and unsignalled avoidance impairments following noradrenaline depletion with DSP4: An hypothesis incorporating and associative and a non-associative factor

Four experiments were performed to investigate the effect of a single prior administration of the selective noradrenaline neurotoxin, DSP4 (50 md/kg, i.p.), upon signalled and unisgnalled variations of the two-way active avoidance procedure. Noradrenaline depletio following DSP4 caused a significant impairment in the acquisition but not in the retention of signalled avoidance. Two unsignalled discrete trial avoidance procedures were used, one of which the 50/10 procedure, was designed to be considerably more difficult than the other, the 50/40 procedure. DSP4- treated rats were found to be impaired on the difficult 50/10 task but not on the 50/40 task. It was also shown that the DSP4 group in the 50/10 experiment made fewer crossings that did not result in shock postponement ('nonreinforced' or intertrial crossings) while in the 50/40 experiment the DSP4 group in the 50/10 experiment made fewer crossings that did not result in shock postponement ('nonreinforced' or 'intertrial' crossings) while in the 50/40 experiment the DSPS group made more 'intertrial' crossings. Response latencies were not significantly altered as a result of the treatment in both instances. The results of the present experiments in conjunction with much accumulate evidence from several other investigations were assimilated in order to develop an hypothesis to account for the consistent signalled two-way avoidance deficits resulting from DSP4 administration. This hypothesis incorporates two main components: (1) It may be that DSP4-treated rats are unable to develop the correct coping behaviour required in the stressful task confronting it, i.e. they fail to make the appropriate crossing (running) respose whether an escape or an avoidance response; (2) It is possible that DSP4-treated rats may fail to associate adequately a successful avoidance response with either the tone that signals shock or the postponement of shock.     

Lean and mean rats: Some effects of acute changes in the food supply upon territorial aggression

In experiment 1, individually housed rats subjected to short-term food restriction displayed more territorial aggression toward conspecific intruders than controls maintained on a free-feeding diet. In experiment 2, small groups of three adult male rats had access to either a standard laboratory diet or the standard diet plus sucrose. Groups with the sucrose supplement were significantly less aggressive toward intruders than controls. Sucrose availability did not produce appreciable gains in body weight but it did reliably decrease within-colony weight variation. The results suggest the existence of an effective dietary mechanism that enables a social species such as Rattus norvegicus to tolerate each other in dense feeding aggregations when food is abundant. Conversely, when food is limited, social intolerance increases and serves to limit the development of large feeding groups.     

Effects of environmental enrichment on spatial memory and neurochemistry in middle-aged mice

The present study compared the effects of environmental enrichment on spatial memory, glutamic acid decarboxylase (GAD) activity, and synaptophysin levels in middle-aged male and female mice. Prior to testing, a subset of 18-month-old male and female C57BL/6 mice was housed with two to three toys and a running wheel in the home cage for up to 29 d. Adult mice (7 mo) of both sexes and the remaining middle-aged mice were group (social) housed, but not exposed to enriching objects. After the enrichment period, all mice were tested in a 1-day version of the Morris water maze, in which both spatial and nonspatial memory were assessed. Immediately after testing, the hippocampus and frontoparietal cortex were dissected, and GAD activity and synaptophysin levels were measured. Environmental enrichment reduced the age-related impairment in spatial acquisition and retention; relative to adult social controls, middle-aged enriched mice were unimpaired, whereas middle-aged social controls were impaired. This reduction was similar in middle-aged males and females. Enrichment did not affect cued memory in either sex. Although hippocampal GAD activity was increased by enrichment in males, all other neurochemical measurements were unaffected by enrichment or aging in either sex. These data suggest that environmental enrichment initiated at middle age can reduce age-related impairments in spatial memory in males and females, although the underlying neurobiological mechanisms of this effect remain unknown.     

A Study of the Effects of Restraint Stress on Colitis Induced by Dextran Sulphate Sodium in Singly Housed Rats

The inflammatory bowel diseases (Crohn's disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made. RESULTS: Rats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight. CONCLUSION: There is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.     

Synaptic plasticity and the organization of behaviour after early and late brain injury.

Hebb proposed that synaptic change underlies behavioural and cognitive plasticity. When applied to recovery from brain injury, the general hypothesis is that if there is recovery following brain injury, then there ought to be a correlated synaptic change, which is presumed to be responsible for recovery. In contrast, if recovery fails to occur, or expected recovery is blocked in some manner, then the synaptic change will likely not be present. Systematic study of functional recovery and synaptic change following brain injury at different ages supports these predictions. Good recovery is always correlated with enhanced connectivity whereas poor recovery is always correlated with an absence of reorganized connectivity. Furthermore, factors that stimulate recovery, such as neurotrophins or experience, stimulate synaptic change and functional recovery. Factors that retard recovery, such as depletion of neuromodulators, also block synaptic change. These results thus support Hebb's general idea that synaptic plasticity is related to behavioural change.     

Social factors influence haloperidol-induced catalepsy in rat

This study employed manipulations which presumably influence social interactions in rats: (1) paired housing with a heavier conspecific and (2) exposure to the odors of other rats. The dependent variable was the akinetic state induced by haloperidol, a neuroleptic and dopamine antagonist. In Experiment 1, adult male Long-Evans hooded rats were matched by weight and caged alone or in pairs with one rat 30 g heavier than its cagemate. All rats received haloperidol (1.5 mg/kg) and catalepsy testing. Heavy rats showed more catalepsy than the lighter member of pairs or weight-matched, singly housed controls. In Experiment 2, adult male rats were left unrecaged or were recaged into cages with bedding recently soiled by females or other adult males. After haloperidol (1.0 mg/kg), the rats exposed to bedding soiled by other adult males showed more catalepsy than did the control groups. Thus, the results of both experiments indicated that social factors can influence the akinesia induced by dopamine antagonists.     

Modulation by 6-hydroxydopamine of expression of the phenylethanolamine N-methyltransferase (PNMT) gene in the rat heart during immobilization stress

Phenylethanolamine N-methyltransferase (PNMT) is the final enzyme in the catecholamine synthesizing cascade that converts noradrenaline (NA) to adrenaline (Adr). Both of these catecholamines are physiologically important hormones and neurotransmitters in mammals with profound influence on the activity of the cardiovascular system. Although PNMT activity and gene expression have been reported in the neonatal and also adult rat heart, little is known about the identity of the cells expressing PNMT mRNA. In this study, we have shown that besides PNMT in neuronal and intrinsic cardiac cells, this enzyme is expressed also in rat cardiomyocytes, as shown by immunofluorescence in isolated cardiomyocytes. To determine which cells in the heart more sensitively show stress-induced changes in PNMT mRNA expression, we performed chemical sympathectomy by administration of 6-hydroxydopamine (6-OHDA), which destroys catecholaminergic terminals. We determined PNMT mRNA levels in the left atria and ventricles of control and stressed rats. In the rats treated with 6-OHDA, PNMT mRNA levels were not changed under normal, physiological conditions compared to vehicle treated rats. Similar results were observed on isolated cardiomyocytes from control and 6-OHDA treated rats. However, 6-OHDA treatment prevented immobilization-induced increase in PNMT mRNA expression. The results allow us to propose that in the heart, the immobilization-induced increase in PNMT gene expression is probably not in cardiomyocytes, but in neuronal cells.     

A study of the effets of restraint stress on colitis induced by dextran sulphate sodium in singly housed rats

The inflammatory bowel diseases (Crohn’s disease and ulcerative colitis) are multifactorial diseases. Clinical reports indicate that emotional stress may contribute to the onset, progression and remission of these diseases. Using an experimental animal model of ulcerative colitis, the effect of stress on the development of and recovery from symptoms, was studied prospectively. Singly housed rats received 4 percent dextran sulphate sodium orally until, fecal blood was detected, indicating the presence of colonic erosions. Tap water was then administered until there were no signs of fecal blood. Two hours of restraint stress were administered daily over four successive days, either prior to or after the induction of colitis. Latencies in days to symptom development and recovery were compared to an unstressed, group. Daily measures of fluid-intake, body-weight, and hemoglobulin in feces were made. Results  Rats exposed to restraint stress procedures prior to induction of colitis had shorter latencies to development of symptoms. There was no significant difference in latency to recovery. The amount of fluid-intake did not significantly differ between groups, nor did the groups differ in body-weight. Conclusion  There is an effect of stress on the latency to develop colitis induced by dextran sulphate sodium. This preliminary study suggests that the impact of stress may be one factor underlying the emergence of ulcerative colitis.     

The effects of naloxone and cage size on social play and activity in isolated young rats

The effects of large and small housing environments as well as naloxone on social play (as defined by pinning behavior) in isolated postweanling male rats were investigated. Animals housed in small cages played significantly more than those housed in larger cages. This effect was not observed when cage size was reversed. Administration of 0.5, 1.0, and 5.0 mg/kg of naloxone resulted in significant decreases in play behavior as compared to saline controls, both before housing environments were switched, and after. Animals in both isolation conditions were also compared to animals that were socially housed. Isolation was found to increase social play as well as the time spent in active social interaction, but had no effect on locomotor activity. While housing in a small cage increases play behavior, it had no effect on the amount of time spent in active social interaction or on activity. While administration of 0.5, 1.0, and 5.0 mg/kg naloxone to habituated animals differentially housed did not result in an overall decrease in activity, when compared with saline controls, only those animals housed in small cages and injected with the high dose of naloxone differed significantly from controls. In animals having no prior play experience, the activity of animals housed in the large and small cages differed significantly from each other only in the saline and 5.0 mg/kg naloxone conditions. Since naloxone's effect on play behavior was strong, but its effect on activity was not profound, our data suggest that naloxone primarily affects the affective component of play rather than altering activity levels.