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Query: UNIPROT:Q86TM3 (cage)
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Excessive alcohol drinking is often linked to the experience of stress, but experimental approaches using animal models of alcohol self-administration have had widely varying outcomes. The objective was to determine how daily exposure to brief, predictable social stress would change alcohol self-administration in rats in a daily limited access protocol. Male Long-Evans rats had either access to a 10% ethanol solution for 15 min in the home cage setting (n=20) or were reinforced with 15% ethanol deliveries for every fifth lever press (n=10). Subsequently, all rats were subjected to brief social stress for five consecutive days. Social stress consisted of attacks by an opponent for 5 min followed by exposure to threats while in a protective cage for 30 min. In both the home cage drinking and operant conditioning groups, social stress exposure significantly decreased alcohol intake or rate of alcohol reinforcements, respectively. When alcohol intake was scheduled immediately before social stress (i.e., 24 h after the previous social stress episode), a decrease was observed with a delay of 1 or 2 days. When alcohol intake was scheduled 4 h after stress, no changes in intake or alcohol reinforcements were observed. Animals that consumed a low dose of ethanol displayed less defensive behavior during social stress compared to water-drinking animals, and showed an increased startle reflex at 8 and 56 h after discontinuation of daily ethanol access. The current experimental protocols of social defeat stress reveal a transient suppression rather than a facilitation of alcohol consumption.
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PMID:Persistent suppression of ethanol self-administration by brief social stress in rats and increased startle response as index of withdrawal. 1143 55

Testosterone (T) and pregnane neurosteroids can enhance conditioned place preference (CPP). The present experiment examined CPP produced by T and its androgenic metabolite dihydrotestosterone (DHT) and 3alpha-Androstanediol (3alpha-diol; an androstane neurosteroid). Administration of 3alpha-diol (>DHT>T) to intact male Long-Evans rats, 1.0 mg daily for six days, 30 min prior to exposure to the non-preferred side of the CPP chamber significantly increased preference for the non-preferred side of the chamber compared to that seen in home cage controls. Levels of circulating 3alpha-diol were increased significantly in 3alpha-diol>DHT>T-administered rats, compared to rats that had vehicle administered or androgen-administration discontinued. Androgen administration decreased seminal vesicle weight and intrahypothalamic androgen receptor (AR) binding compared to that seen in rats that had vehicle administered or androgen-administration discontinued. Testosterone, DHT, and 3alpha-diol decreased GABA-stimulated chloride influx in cortical synaptoneurosomes, and muscimol binding in the hippocampus compared to that seen in rats with vehicle administered or that had androgen-administration discontinued. These data indicate that administration of 3alpha-diol is more effective at enhancing CPP and increasing circulating 3alpha-diol levels than is DHT or T administration, and that all of the androgen regimens employed decreased peripheral and hypothalamic androgen receptor binding and cortical and hippocampal GABA(A) receptor function. Hence, whether the effects of 3 alpha-diol on CPP are mediated by differential actions at ARs or GABA(A) receptors in particular brain regions needs to be determined.
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PMID:The testosterone metabolite and neurosteroid 3alpha-androstanediol may mediate the effects of testosterone on conditioned place preference. 1150 Feb 54

Intradentate injection of colchicine is one of the techniques used to destroy granule cells. This study compared the behavioral effects of various amounts of colchicine (1.0, 3.0, and 6.0 microg; Col 1, Col 3, and Col 6, respectively) injected into the dentate gyrus of adult Long-Evans male rats. Starting 10 days after lesion surgery, behavioral testing assessed home-cage and open-field locomotion, alternation in a T-maze, water-maze, and radial-maze learning according to protocols placing emphasis on reference, and working memory. All of these tasks are sensitive to hippocampal disruption. Histological verifications showed that the extent of the lesions depends on the dose of colchicine (index of dentate gyrus shrinkage: -33% in Col 1, -54% in Col 3, and -67% in Col 6 rats). Colchicine dose-dependently increased nocturnal home cage activity (an effect found 10 days but not 5 months after surgery), but had no significant effect on open-field locomotion or T-maze alternation. A dose-dependent reference memory impairment was found during the acquisition of spatial navigation in the water maze; Col 3 and Col 6 rats were more impaired than Col 1 rats. During the probe trial (platform removed), control rats spent a longer distance swimming over the platform area than all rats with colchicine lesions. In the working memory version of the test, all rats with colchicine lesions showed significant deficits. The deficits were larger in Col 3 and Col 6 rats compared to Col 1 rats. The lesions had no effect on swimming speed. In the radial-maze test, there was also a dose-dependent working memory impairment. However, reference memory was disrupted in a manner that did not differ among the three groups of lesioned rats. Our data are in line with the view that the dentate gyrus plays an important role in the acquisition of new information and is an integral neural substrate for spatial reference and spatial working memory. They also suggest that damage to granule cells might have more pronounced effects on reference than on working memory in the radial maze. Finally, they demonstrate that part of the variability in the conclusions from previous experiments concerning the role of granule cells in cognitive processes, particularly in spatial learning and memory, may be due to the type of tests used and/or the extent of the damage produced.
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PMID:Cognitive performances and locomotor activity following dentate granule cell damage in rats: role of lesion extent and type of memory tested. 1152 55

Locomotor activity measures are often used in behavioral neuroscience. There is, however, a large variability in the protocols assessing locomotor activity which may, more or less, strongly be influenced by exploration and reactivity to novelty in unfamiliar situations. Using Long-Evans male rats, we investigated how far changes, such as placing rats in a cage physically identical to the home cage supplied with fresh sawdust but kept in a familiar room, or placing the familiar home cage with the rat inside in another (unfamiliar) room, may influence the level of locomotor activity. We showed that both changes resulted in significantly increased locomotion in the first 2 h after placing the rats in the respective test situation, but there is no significant additive effect. These changes performed right before the start of the test do not alter diurnal or nocturnal locomotor activity once the first 2 h have elapsed. The results illustrate that rats kept in an environment with stable proximal features (cage, sawdust) can react by increased activity in response to more distal novelty (experimental room), and conversely, that rats in a familiar environment react to proximal changes in the home cage.
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PMID:Effects of room and cage familiarity on locomotor activity measures in rats. 1156 45

We explored the effects of short, intermediate, and continuous social stress on daily ethanol and water intake in rats. The study was designed to: (1) detect increases in intake during hours when animals were not stressed; and (2) detect shifts in preference from solutions with high to low alcohol content. Male Long-Evans rats acquired ethanol self-administration using a sucrose-fading procedure, which was followed by continuous access to 10% and 3% ethanol solutions and water. After intake stabilized, rats were exposed to three periods of five consecutive days of social stress, with 8-10 days without stress in between. Short social stress consisted of being attacked and defeated by an aggressive opponent, followed by 30 min exposure to threats by the aggressive male while in a protective cage. Intermediate and continuous social stress consisted of a 6 h or 24 h 'threat of attack' exposure, respectively. All stress exposures reduced daily intake of 10% ethanol, did not cause changes in intake of 3% ethanol, and caused increases in water intake. No compensatory ethanol consumption was observed on stress days or after stress exposure was discontinued. These results are at variance with the hypothesis for increased alcohol consumption during or following social stress episodes.
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PMID:Short or continuous social stress: suppression of continuously available ethanol intake in subordinate rats. 1171 Jul 48

Behavioral manipulations such as housing in an enriched environment have been shown to increase brain weight and visual cortical thickness. The present study was designed to test whether skill learning or repetitive movements can alter the thickness of the motor cortex. One group of 6-mo-old Long-Evans female rats learned motor skills on an obstacle course that increased in difficulty over training and required balance and coordination. A second group ran voluntarily in exercise wheels attached to their home cage but had little opportunity for skill learning. The third group was handled daily but received no opportunity for learning or exercise. Each condition lasted 26-29 d. The skill-learning and exercise conditions had greater heart weight, and the exercise condition had greater adrenal gland weights than controls. The thickness of the motor cortex was measured in four coronal planes between -2.33 mm to -0.3 mm from bregma. Regions of interest that corresponded to published maps of forelimb and hind-limb representations were analyzed together. Rats in the skill-learning condition had significantly thicker medial cortical areas in the two anterior planes (-0.8 and -0.3 mm from bregma). These regions correspond to previously mapped hind-limb representations. The exercise group had greater thickness of the medial region at -0.8 mm from bregma. Cortical thickness in all conditions varied significantly along the medial to lateral axis. For both treatments, the effects were restricted to medial and anterior regions of interest rather than posterior or lateral regions of interest. The results indicate that robust exercise, in addition to skill learning, is capable of altering the thickness of the motor cortex, but that the effects are restricted rather than distributed within the regions studied.
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PMID:Alterations in the thickness of motor cortical subregions after motor-skill learning and exercise. 1191 1

A total of 32 male Long-Evans rats were tested on a modified version of Flaherty, Turovsky, and Krauss's (1994) anticipatory contrast paradigm to assess pattern separation for reward value. Prior to testing, each rat received either a control, a hippocampal, or an amygdala lesion. In the home cage, each rat was allowed to drink a water solution containing 2% sucrose for 3 min followed by a water solution containing 32% sucrose for 3 min. Across 10 days of testing, the rats in each lesion group showed significantly increased anticipatory discriminability as a function of days. To assess the operation of a pattern separation mechanism, each rat was then tested using the same procedure except the 2% solution was followed by a 16% solution for 10 days and then by an 8% solution for 10 days. Control and hippocampal-lesioned rats continued to show high discriminability when the 2% solution was followed by a 16% solution; however, the amygdala-lesioned rats showed low anticipatory discriminability. On trials where the 2% sucrose solution was followed by an 8% sucrose solution, all groups showed low discriminability scores, suggesting that when two reward values are very similar even control animals are not able to separate the reward values in memory. However, the results of a preference task revealed that all groups can perceptually discriminate between a 2% and an 8% sucrose solution. The data suggest that the amygdala but not the hippocampus is involved in the separation of patterns based on reward value.
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PMID:The amygdala but not the hippocampus is involved in pattern separation based on reward value. 1199 62

Rats placed in an environment other than their home cage increase their body temperature (Tb) by more than 1 degree C. This stress-induced hyperthermia is considered to be a fever, in the sense that the Tb rise seems to reflect an upward shift in the level of regulated Tb (set point). The circadian rhythm of Tb also reflects changes in set point. One might therefore expect to see differences in response to such stress during various phases of the light-dark (LD) cycle as Tb fluctuates between L and D. To test this, 3- to 6-month-old male Long-Evans rats were taken from their home cages (12:12 LD) and placed individually in a Plexiglas container for 30 min. Tb and activity were measured via telemetry. In the first experiment, rats were placed in the container during day (from 1 to 3 h after lights on) and night (from 1 to 3 h after lights off), with light on or off during the test. There was a significant Tb rise in response to placement in the container at all times except when the rats were tested during the night with light on in the container; in that condition there was no Tb rise. In the second experiment, the authors determined that 30 min of light in the home cage before the test did not affect Tb: If the light was on in the test situation, hyperthermia was inhibited, and if it was off, hyperthermia was as high as control levels. In the third experiment, to determine whether this effect was time dependent, the test was performed at 4-h intervals, with light on or off during the test. The strongest inhibiting effect of light was in early night. In the fourth experiment, the authors turned the lights on during early night while the rats were in their home cages. This reduced their Tb significantly by less than 0.3 degrees C. The authors conclude that both clock time and light condition during testing are factors affecting the Tb rise in response to stress.
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PMID:Stress-induced hyperthermia depends on both time of day and light condition. 1200 63

Twenty days of complex motor skill training in adult rats was previously demonstrated to rehabilitate motor performance deficits induced by binge alcohol exposure in neonatal rats. This follow-up study evaluated morphological plasticity in the paramedian lobule of the cerebellum (PML) using the same treatment and training regimens. On postnatal days (PD) 4-9, female Long-Evans rats were given either alcohol (Alcohol Exposure - AE, 4.5 g/kg/day via artificial rearing), exposure to gastrostomy control (GC) artificial rearing procedures, or reared normally as suckle controls (SC). After weaning, all rats were housed two to three per cage. At 180 days old, rats were randomly assigned either to a rehabilitation condition (RC: given 20 days of complex motor skill training), or to an inactive condition (IC: remained in their home cage). The AE rats were delayed in acquiring the training, but there were no group differences in performance over the last 2 weeks of training. Unbiased stereological techniques were used to evaluate PML volume, Purkinje cell and parallel fiber synapse density. Although total volume of PML was significantly reduced in the AE rats, complex motor skill training resulted in a significant increase in the PML molecular layer in all three postnatal treatment groups. The RC animals from the SC and AE groups had more parallel fiber synapses per Purkinje cell than corresponding IC animals. These data support the hypothesis that 'rehabilitative' motor training stimulates synaptogenesis in the PML, and that Purkinje neurons that survive the early postnatal alcohol insult are capable of substantial experience-induced plasticity.
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PMID:Therapeutic effects of complex motor training on motor performance deficits induced by neonatal binge-like alcohol exposure in rats: II. A quantitative stereological study of synaptic plasticity in female rat cerebellum. 1202 Aug 66

Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 microg 192-IgG-saporin in 0.4 microl phosphate-buffered saline. Control rats received an equivalent amount of phosphate-buffered saline. Starting 2 weeks after surgery, all rats were tested for locomotor activity in their home cage, beam-walking performance, T-maze alternation rates (working memory), reference and working memory performance in a water-maze task, and memory capabilities in the eight-arm radial maze task using uninterrupted and interrupted (delay of 2 min, 2 h and 6 h after four arms had been visited) testing procedures. Histochemical analysis showed a significant decrease of acetylcholinesterase (AChE)-positive reaction products (30-66%) in various cortical regions at the 0.2-microg dose. At the dose of 0.4 microg, there was an additional, although weak, damage to the hippocampus (17-30%) and the cingulate cortex (34%). The behavioral results showed only minor impairments in spatial memory tasks, and only during initial phases of the tests (reference memory in the water maze, working memory in the radial maze). The behavioral effects of the dramatic cholinergic lesions do not support the idea of a substantial implication of cholinergic projections from the NBM to the cortex in the memory processes assessed in this study, but they remain congruent with an involvement of these projections in attentional functions.
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PMID:Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats. 1217 91


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