Social contacts and production of 50-kHz short ultrasonic calls in adult rats

The goal of the study was to provide evidence that the production of 50-kHz calls by adult rats is driven by potential or direct social contacts. The calls have been studied during daily visits to a cage by single or paired rats. Repeated exposure of rats to the cage frequently visited by other rats or direct contact between rats significantly increased the number of 50-kHz calls. The increase in production of 50-kHz calls was reduced by 78% after intrapreoptic-anterior hypothalamic injection of MK-801, an N-methyl-D-aspartate-type glutamate receptor antagonist. Calls emitted in all situations had a similar acoustic profile. It was found that 50-kHz calls were produced in anticipation of, and/or during, direct social contacts among adult rats and were predominantly initiated by olfactory stimuli. The calls seem to express an appetitive behavioral state in which the central glutamatergic mechanism is implicated.     

Maintenance-feeding effort affects instrumental performance

The effort required of rats to obtain food, employing standard maintenance-feeding procedures, can affect the effort subsequently expended in an instrumental-learning task. Rats received 43 food-rewarded runway trials followed by access to food (a) on the home-cage floor, or (b) from a hopper attached to the home-cage's wiremesh front wall. Hopper feeding involved the greater effort since the rats had to gnaw the food pellets through the wire mesh. Following 9 or 27 days of maintenance feeding, the rats were returned to the runway for one rewarded trial and 16 extinction trials. The hopper-fed rats ran faster than floor-fed rats on the rewarded test trial. In extinction, long-term maintenance feeding produced faster subsequent running times by the hopper-fed rats than the floor-fed rats. Short-term maintenance feeding, on the other hand, produced slower running times by the hopper-fed rats than the floor-fed rats. The results are consistent with previous findings of transfer of effort across behaviours and suggest that the effort required for reinforcement in the maintenance environment can systematically influence the effectiveness of various experimental treatments.     

Active regulation to be lean by rats with ventromedial hypothalamic lesions.

Adult female Long-Evans rats with direct-current electrolytic or radio-frequency thermocoagulatory lesions of the ventromedial hypothalamus (VMH) lived on pellet fragments or a powdered chow containing as much as 1.2% quinine sulfate by weight or lived in Skinner boxes with 45-mg Noyes pellets delivered contingent on fixed ratios (FR) of lever pressing up to FR 128. As had been found previously for intact rats, the body weights maintained by VMH rats were determined by the percentage of quinine sulfate in or the contingency of reinforcement of the food on which they lived. Even when the rats lived on highly adulterated or response-contingent food and were lean, they ate more of that food when the ambient temperature was reduced and less of that food during several weeks of forced feeding of eggnog by gavage. Weight maintenance in the cold and caloric compensation during forced feeding were as precise for VMH rats eating highly adulterated chow or Noyes pellets contingent on high fixed ratios of lever pressing as for VMH rats eating typical laboratory chow ad lib, even though the former rats at the time maintained weights no greater than intact rats and the latter rats at the time were grossly obese. Furthermore, regulation in the cold or during forced feeding was in general only a little less precise for the rats with lesions than for intact rats. It may be as characteristic of VMH rats that they eat to become lean and remain lean as that they eat to be obese. The diets of both intact and VMH rats in some manner determine the adiposities that rats will defend against caloric challenge.     

Pharmacological manipulations of brain catecholamines and the aggressive behavior induced by marihuana in REM-sleep-deprived rats

A marihuana extract, apomorphine, and amphetamine provoked in rats previously deprived of REM sleep for 96 hr an upright position with the animals pawing each other as in fighting. Nondeprived rats injected with the drugs did not show this aggressive behavior. The marihuana-treated animals also bit vigorously a rod introduced into the cage, a fact not observed with the apomorphine-treated rats. These data suggest that the marihuana aggressiveness could at least partially be mediated through the brain catecholamines. Haloperidol, chlorpromazine, α-methyl-p-tyrosine, and reserpine decreased the marihuana aggressiveness of the deprived rats. Increase of dopamine concentration by previous treatment with Dopa potentiated aggressiveness. Blockade of norepinephrine synthesis by FLA-63 was ineffective in reducing marihuana aggressiveness in the REM-sleep-deprived rats. Actually, in these animals aggressiveness appreared even without the marihuana injection. Phenoxybenzamine partially blocked marihuana aggressiveness but also severely depressed the rats. However, 20 mg/kg alone succeeded in provoking aggressiveness in the deprived rats. It is suggested that in rats with neural excitability heightened by previous REM-sleep deprivation dopamine facilitates aggressive behavior, an effect inhibited by porepinephrine. This hypothesis would imply that marihuana induces aggressiveness in REM-sleep-deprived rats by inhibiting, through an as yet unknown mechanism, the central norepinephrine system.     

慢性应激诱导的抑郁大鼠纹状体par-4基因的表达

为研究慢性温和应激诱导的抑郁大鼠纹状体内前列腺凋亡反应蛋白(prostate apoptosis response-4, par-4)的表达, 及甲基化是否参与par-4基因表达的调控, 将10周龄大鼠随机分为实验组和对照组, 实验组接受慢性温和应激, 对照组不接受实验性处理。于大鼠13周龄时, 采用强迫游泳、糖水偏爱测验测定大鼠的抑郁水平, 以实时定量PCR检测纹状体par-4及多巴胺D2受体(Dopamine receptor D2, DRD2) mRNA表达水平, 免疫印迹法检测纹状体par-4蛋白质表达水平, 用亚硫酸盐测序法检测par-4基因启动子区甲基化水平。结果发现, 与对照组大鼠相比, 实验组大鼠漂浮时间延长, 糖水偏爱率降低, 脑纹状体par-4、DRD2 mRNA及par-4蛋白质表达水平均降低, par-4基因启动子区甲基化水平两组差异不显著。提示慢性温和应激诱导大鼠产生了抑郁样行为, 并能抑制纹状体par-4基因的表达, 而基因甲基化可能并不参与其调控机制。     

Protein deficiency magnifies social influence on the food choices of Norway rats (Rattus norvegicus)

The food choices of protein-deprived juvenile rats were more profoundly affected by interaction with conspecifics than were the food choices of protein-replete juvenile rats. When choosing among four different-flavored, protein-deficient diets, protein-deprived rats ate significantly more of the diet eaten by a conspecific demonstrator than did protein-replete rats. These data suggest that the food choices of the relatively less successful members of a population are most affected by social interaction. Consequently, the mean effect of social interaction on diet selection in a population of Norway rats is likely to be positive.     

Open Field Motor Patterns and Object Marking, but Not Object Sniffing, Are Altered by Ibotenate Lesions of the Hippocampus

Objectmarking and object sniffing were assessed in an open field during six 5-min trials in unoperated Long-Evans rats and rats with ibotenate lesions of the hippocampus and/or neocortex. Object marking was higher in hippocampally lesioned rats than in unoperated rats. Object marking did not differ between neocortically lesioned rats and unoperated rats. Object sniffing durations and visits did not differ between unoperated and hippocampally lesioned rats nor between unoperated and neocortically lesioned rats. A new object elicited longer sniffing by both unoperated and hippocampally lesioned rats. Neocortically lesioned rats did not show this effect. There were no effects of the new object on marking. Computerized tracing of open field paths revealed a smaller perimeter track for hippocampally lesioned rats than for unoperated rats. This difference reflected distinct ambulatory patterns. Hippocampally lesioned rats made stereotyped hind-limb pivots at each corner, while normal rats used forelimb pivots or reared and reoriented adjacent to the wall. Rearing was lower in hippocampally lesioned rats, and higher in neocortically lesioned rats, than in unoperated rats. These data indicate that investigative object behavior (sniffing) is resistant to the effects of hippocampal damage, while object-elicited marking and motoric output may be profoundly altered. The data on sniffing suggest either that (1) the noticeability of the objects used elicited investigative behaviors in hippocampally damaged rats comparable to those of novelty-induced exploration in normal rats or (2) object exploration is not used to create a spatial map, and, hence, not disturbed by hippocampal loss. Object marking may require spatial locale information to be exercised normally, or may index the mediation of an olfactory-modulated behavioral pattern through the hippocampal system.     

Anxiety in rats selectively bred for Fast and Slow kindling rates: situation-specific outcomes

Rats selectively bred for amygdala excitability, realized by fast or slow kindling epileptogenesis, were previously reported to exhibit differential levels of anxiety. Although the Slow kindling rats generally appeared more anxious in several behavioral tests, under certain test conditions the Fast kindling rats displayed greater anxiety or stressor reactivity. The present investigation confirmed that in a test of anxiety comprising suppression of consumption of a palatable snack in an unfamiliar environment, the Slow kindling rats exhibited greater anxiety and that this effect was attenuated by diazepam. Likewise, the acoustic startle response was greater in the Slow kindling rats. However, the fear-potentiated startle response was more pronounced in Fast kindling rats, particularly among females, irrespective of whether the test parameters elicited moderate or high startle amplitudes. The elevated startle in the Slow rats, and the fear potentiated startle in the Fast rats, were attenuated by diazepam. These data indicate the need to differentiate subtypes of anxiety in animal models, and raise the issue that anxiety elicited by specific environmental triggers may interact with genetically determined trait characteristics.     

Lactation deficit in OFA hr/hr rats may be caused by differential sensitivity to stress compared with Wistar and Sprague Dawley rats

OFA hr/hr (OFA) rats present a major lactation deficit that impairs offspring survival. To explore whether abnormal stress responsiveness causes this deficit, we compared their hormonal (prolactin, progesterone, and corticosterone) responses to stress (room change and 2-min ether exposure) with those of Wistar and Sprague Dawley (SD) rats. We tested responses during the estrous cycle, pregnancy, lactation, after ovariectomy, and ovarian steroid hormone priming, and responses to suckling. We evaluated hypothalamic expression of receptors for prolactin (PRLRlong) and the isoforms of receptors for progesterone (PRA and B) and estrogen (ERα and β) in late pregnancy. We tested whether administration of an anxiolytic (diazepam) improved lactation. Ether exposure increased circulating levels of the three hormones in the three strains of rats, cycling and ovariectomized, but was less effective in pregnancy and lactation. Elevated estrogen level (estrus and estradiol-treated ovariectomized rats) potentiated the prolactin response more in SD and OFA rats than in Wistar rats. Elevated progesterone level (late pregnancy, lactation, progesterone-treated ovariectomized rats) inhibited the prolactin response less in OFA than in SD or Wistar rats. Ether exposure inhibited the prolactin and oxytocin responses to suckling only in OFA rats. Diazepam treatment increased pup survival rate and the prolactin response to suckling. Hypothalamic total PR mRNA content, assayed by RT-PCR, was higher in pregnant OFA rats compared with SD and Wistar rats, but the PRB/PRA protein ratio determined by Western blot was lowest in Wistar rats, intermediate in OFA rats, and highest in SD rats. The heightened sensitivity to stress of lactating OFA rats may contribute to their lactational deficit and be caused by a combination of hypoprolactinemia and reduced inhibitory capacity of progesterone.     

Crowding-induced changes in basal and stress levels of thyrotropin and somatotropin in male rats

The effects of crowding on thyrotropin (TSH) and somatotropin (GH) secretion were studied in two-month-old male rats. Crowded rats (9-10 per cage) showed lower serum GH levels than controls (3 per cage). Likewise, serum GH was lower in crowded rats after acute exposure to stress. However, percentage inhibition of GH secretion induced by acute stress was similar in crowded and control rats. Crowding reduced the TSH response to acute stress. The results found with the administration of hypothalamic regulatory factors suggest that the impaired GH and TSH secretion observed in crowded rats was not likely to be at the pituitary level. Therefore, altered neuroendocrine control of GH and TSH secretion appears to exist in crowded rats. Preliminary results obtained in rats crowded from weaning to adulthood suggest that food restriction only partially accounts for the changes observed in crowded rats.     

右旋柠烯对幼鼠颞叶癫痫海马星形胶质细胞的影响

探讨右旋柠烯（D-L）对癫痫幼鼠海马星形胶质细胞胶质原纤维酸性蛋白（GFAP）的影响。利用尼氏染色及免疫组化技术观察匹罗卡品致癫痫的幼鼠经药物（左乙拉西坦、丙戊酸钠、D-L）治疗后星形胶质细胞形态学变化和GFAP的表达。尼氏染色显示药物治疗后幼鼠海马胶质神经元脱失较未治疗的幼鼠明显减轻;海马GFAP免疫阳性细胞数在药物治疗后的幼鼠较未治疗幼鼠明显减少（P〈O．05）。幼鼠癫痫发作可能与海马星形胶质细胞增生有关,D-L对发育期大鼠颞叶癫痫星形胶质细胞的增生及GFAP的表达似有抑制作用,推测D-L可能具有抗癫痫作用。     

Male HIV-1 transgenic rats show reduced cocaine-maintained lever-pressing compared to F344 wildtype rats despite similar baseline locomotion

The HIV-1 transgenic (Tg) rat model is valuable for understanding HIV-associated neurocognitive disorders (HAND) and accompanying substance use and misuse. Tg and F344/NHsd wildtype (WT) rats were allowed to self-administer intrajugular cocaine. For the first 7 sessions, neither genotype self-administered cocaine (0.1 mg/kg/infusion) on a fixed ratio 1 schedule. We thus implemented a lever–cocaine “autoshaping” session followed by a series of manipulations changing dose and reinforcement schedule. Tg rats self-administered much less cocaine than WT rats throughout the study. Of 8 Tg rats, 5 modestly increased self-administration from sessions 36–50. Of those, only 3 showed a lever discrimination. Of 10 WT rats, 8 acquired robust self-administration by session 19; all WT rats self-administered cocaine by the end of the study. WT and Tg rats had similar baseline locomotor activity in the self-administration chamber suggesting that the low levels of cocaine intake in the Tg rats did not reflect a nonspecific motor impairment in this rat strain. Concomitant measurement of activity with self-administration revealed activity increases that followed increased cocaine intake. That relation held in Tg rats. Therefore, the present study provides evidence that HIV-1 Tg rats are less sensitive to the reinforcing effects of cocaine than their F344 WT counterparts.     

Accelerated cognitive aging in diabetic rats is prevented by lowering corticosterone levels

Diabetes and normal aging are both characterized by increases in levels of glucocorticoids. Because long-term exposure to elevated glucocorticoids can be detrimental to hippocampal function, we evaluated the performance of young diabetic rats in the 14-unit T-maze, a task that is sensitive to hippocampal deficits. To assess the contribution of diabetes-induced elevations in corticosterone levels, we examined maze learning in diabetic rats that had levels of corticosterone 'clamped' through adrenalectomy and low-dose corticosterone replacement. For comparison, we also tested a separate group of young and aged rats in the maze. Adrenally intact diabetic rats learned poorly in the 14-unit T-maze. Preventing the increases in corticosterone levels that accompanies the onset of experimental diabetes also prevented deficits in complex maze learning. The pattern of errors made by adrenally intact diabetic rats was similar to the pattern of errors made by aged rats, suggesting that the cognitive profiles of diabetic and aged rats share common features.     

Spatial training and high-frequency stimulation engage a common pathway to enhance glutamate release in the hippocampus

We have measured depolarization-induced release of endogenous glutamate in synaptosomes prepared from the dentate gyrus after the induction of LTP by high-frequency stimulation in anesthetized rats, and after training in the water maze. Both spatial training and LTP in untrained rats were accompanied by an increase in glutamate release from dentate synaptosomes. The enhancement of synaptosomal glutamate release induced by high-frequency stimulation was abolished in well-trained rats, and was reduced in partially trained rats and in rats trained in a nonspatial task. However, the magnitude of LTP was similar in well-trained and untrained groups. These results indicate that spatial training activates a glutamate release pathway that converges with that activated in LTP, and demonstrate an unexpected dissociation between increased glutamate release and LTP.     

Conspecific aggression influences food carrying: Studies on a wild population of Rattus norvegicus

Laboratory rats, like many other animal species, transport food. Their behavior is influenced by factors such as food size, the time required to eat, travel distance, travel difficulty, and the availability of cover, etc. Recent versions of optimal foraging theory suggest that species that display such behavioral patterns do so in order to minimize risk to predation while at the same time maximizing food gain. Nevertheless, it is not clear that this explanation applies to rats, nor is it easy to investigate this problem in a laboratory. The results of the present study on urban feral rats show that their food handling behavior is similar to that of domestic rats. The results also suggest that food carrying can serve defensive as well as communicative functions. Aggression around food sources was high. Smaller rats always carried food and some large rats infrequently carried food, suggesting that the food carrying by smaller, subordinate rats may help them avoid conspecific aggression. The rats also vigorously attempted to steal food that was carried home by conspecifics. This result suggests that food carrying can redistribute food resources and inform conspecifics about food availability. The results demonstrate the utility of multilevel behavioral analysis and also demonstrate that for rats, food transport has functions other than predator avoidance, including avoidance of conspecific aggression and communication about food availability. © 1996 Wiley-Liss, Inc.     

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.     

Rats (Rattus norvegicus) selectively bred to differ in avoidance behavior also differ in response to novelty stress, in glycemic conditioning, and in reward contrast

The behavior of the Syracuse high avoidance (SHA) and Syracuse low avoidance (SLA) rats, selectively bred by Brush (F. R. Brush, J. C. Froehlich, & P. Sakellaris, 1979, Behavior Genetics, 9, 309-316) to differ in avoidance behavior, was examined in several different tasks. The SLA rats showed a greater elevation in plasma glucose when exposed to a novel environment; after 7 days of exposure to this environment there was evidence of habituation in the SHA rats but not in the SLA rats; the SHA rats showed a hyperglycemic conditioned response in a glycemic conditioning procedure, the SLA rats showed no evidence of conditioning but had higher overall levels of plasma glucose; both strains showed reliable successive negative contrast effects in consummatory behavior when shifted from 32 to 4% sucrose, but the contrast was larger in the SLA rats; the administration of chlordiazepoxide eliminated negative contrast in the SLA rats but had no effect on contrast in the SHA rats; and the SLA rats were reliably heavier than the SHA rats. The behavioral differences were considered in the context of differences in emotional reactivity between the two strains.     

Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats

Although copper sulfate is an emetic stimulus, preliminary experiments failed to obtain a taste aversion in intact rats following intragastric administration as had been previously reported in the literature. Several experiments were therefore run to further investigate the capacity of intragastric copper sulfate to function as an unconditioned stimulus for taste aversion learning and the role of the vagus in mediating that learning. The results of the first series of experiments showed that intragastric administration of copper sulfate (5 mg/kg X 5H2O) was more effective in reliably producing a taste aversion in vagotomized rats than in sham-operated control rats. The second experiment examined the effects of area postrema lesions on the acquisition of a taste aversion produced by intragastrically administered copper sulfate in vagotomized rats. The results indicated that the taste aversion observed following treatment with intragastric copper sulfate in vagotomized rats could be prevented by lesions of the area postrema. The present results indicate that intragastric administration of copper sulfate is a more reliable unconditioned stimulus for taste aversion learning in vagotomized rats than in intact rats. It is not certain what factors might account for the discrepant results between the present experiments and previously published research.     

Preserved spatial memory in old rats survives 10 months without training

Aged rats with extensive prior training on the radial maze retain the capacity for accurate spatial working memory (WM) for at least 3 months without practice. To investigate the temporal limits of this influence of prior experience we compared the reacquisition of spatial WM by a group of experienced 21.5-month-old rats to the original acquisition by naive 3-month-old rats. The aged rats had received 225 radial maze tests between 3 and 11 months of age. Despite 10 months without practice the old rats rapidly reacquired critical performance. Their reacquisition was markedly superior to original learning by the young rats, even when delays as long as 5 h were imposed between the rats' fourth and fifth choices during the daily tests in the eight-arm maze. Additional tests showed that neither young nor old rats employed a response strategy to maintain accurate spatial WM performance. Experience clearly confers long-lived protection against the otherwise deleterious effects of aging on spatial WM, but the mechanism by which this influence arises is unknown.     

Initial environment influences amphetamine-induced stereotypy: subsequently environment change has little effect

Saline-treated and amphetamine-treated (7 mg/kg, ip, immediate) male rats from a Sprague-Dawley substrain were observed in two test environments designed to elicit different investigative responses in normal rats. Snout contact with the substrate was generated by placing the rat in a small enclosed cage. Absence of snout contact was induced by placement of the rat on a square elevated platform. Detailed ethological records were kept of locomotion, rearing, sitting, grooming, gnawing, and sleeping throughout the 90-min session. Amphetamine-treated rats incorporated environmentally contingent bodily postures into their forms of stereotyped behavior. The postures were characteristic of those evinced initially by the saline-treated rats in the same test environment. The control rats showed appropriate changes in their investigative behavior when the apparatus was changed at 10 and at 30 min postinjection. The amphetamine-treated rats, however, were completely unresponsive to such changes at 30 min and only partially so at 10 min postinjection. It was concluded that there is a temporal gradient of decreasing readiness to modify repetitive behavior after a single, large dose of amphetamine.