Altered grooming responses to stress in rats exposed prenatally to ethanol

The effects of prenatal alcohol exposure on grooming, locomotion, and rearing in response to stress were examined in adult rats whose mothers consumed a liquid diet containing 35% ethanol-derived calories (EDC). Offspring of both pair-fed 0% EDC mothers and ad libitum chow-fed mothers were included as controls. In Experiment 1, females groomed more than males following placement into a novel test chamber, but no differences due to prenatal treatment were observed. Ethanol-exposed animals groomed more than controls following the stress of a forced 1-min swim (Experiment 2), but when rats tested in Experiment 1 were observed again after forced swim stress (Experiment 3), no differences due to prenatal treatment or sex were observed. Experiment 4 examined the effects of pretreatment with 1 mg/kg naloxone on novelty-induced grooming and as in Experiment 1 prenatal treatment did not affect grooming responses. Females again groomed significantly more than males and naloxone reduced grooming equally for all groups. The results suggest that novelty-induced grooming is a sex-influenced behavior, with females grooming more than males, and that animals exposed prenatally to alcohol and tested as adults may have altered responses to certain stressors (i.e., forced swim) under specific conditions. The altered grooming response of alcohol-exposed rats to swim stress can be eliminated by preexposing them to novelty stress.     

Effect of chronic ethanol administration on intermale aggression in rats

An experiment was performed to study the effect of chronic ethanol administration on intermale aggression in rats using a 24-hour resident-intruder test. During the resident-intruder test residents displayed virtually all of the agonistic behaviors, and intruders displayed virtually all of the defensive behaviors. Intruders treated with ethanol displayed more defensive behavior and elicited more agonistic behavior than control intruders. Twenty minutes into the resident-intruder test intruders showed the greatest increase in corticosterone (338% vs. 129%), while residents showed the greatest increase in testosterone (103% vs. 18%). On the 2nd day of the resident-intruder test intruders lost more weight than residents (21.5 g vs. 10.2 g). Plasma corticosterone levels remained elevated for the intruders, and in particular for those intruders displaying defensive behaviors regardless of the resident's behavior. Plasma testosterone levels remained elevated for those residents that were paired with intruders that displayed defensive behaviors regardless of the resident's behavior. The frequency and severity of biting attacks by ethanol residents was significantly greater than that of control residents. In addition, the locus of biting attack shifted from the upper back of intruders paired with control residents to the flanks, tail, lower feet, and ventral surface on intruders paired with ethanol residents.     

Influence of rearing conditions on voluntary ethanol intake and response to stress in rats

The effects of exposure to four environmental rearing conditions on subsequent voluntary ethanol intake and response to immobilization stress were examined. Male weanling rats were reared in an enriched environment, with a female partner, with a male partner, or individually, for 90 days. At 111 days of age, voluntary consumption of ethanol in increasing concentrations (3 to 9%, v/v) was assessed. Following the ethanol-exposure period, rats were randomly divided into stressed and nonstressed groups and exposed to 3 h of immobilization. Results indicated that the enriched animals consumed greater amounts of ethanol as compared to all other groups, suggesting that the enriched environment and not handling, housing conditions, or the presence of another male or female is responsible for the observed increase in ethanol drinking behavior. Ulcer data indicated that among environmentally enriched rats, ethanol attenuated stress ulcer development relative to their non-ethanol-exposed but stressed controls. In nonstressed enriched rats, ethanol alone exacerbated stomach damage. We suggest that environmental rearing conditions markedly influence the complex interaction between ethanol intake and the response to stress.     

Adaptation of anterior pituitary hormones to chronic noise stress in male rats

We have studied the effects of acute and chronic noise on serum levels of pituitary hormones in male Wistar rats. Acute noise increased serum levels of corticosterone, prolactin, and luteinizing hormone and decreased serum GH. FSH was unaffected by this stressor. Chronic noise did not modify basal levels of any hormone studied, however responsiveness of some hormones to the same stimuli was altered. Reduced corticosterone, prolactin, and GH responses to noise was observed after previous chronic exposure to this stimuli. LH response followed the same pattern although it did not reach statistical significance. It might be concluded that adaptation to a repeated stress stimulus is not confined to the pituitary-adrenal axis, however, the degree of adaptation could vary between different hormones.     

The effect of ethanol treatment on social behavior in male rats

The effect of 0.50 g/kg of EtOH in male rats interacting with a stimulus male juvenile in a newly developed test of social interaction was examined. The adult male rats were treated with EtOH (8.0 to 12.0 g/kg/day) or equicaloric dextrin maltose for 2 weeks (studies 1 and 2) or 8 weeks (study 3) and social interaction was assessed both before and after chronic drug treatment was ended in study 1 and after chronic drug treatment was ended in studies 2 and 3. It was found that prior to chronic drug treatment, in study 1, 0.50 g/kg of EtOH increased both aggressive behavior and time spent interacting with the stimulus juvenile male from the first presentation of the juvenile to the second presentation (20 min apart) while saline injection decreased it. After chronic drug treatment was ended, in study 1 animals treated chronically with EtOH were more aggressive when they were not intoxicated than when they had been treated with 0.50 g/kg of EtOH. In studies 2 and 3, after chronic drug treatment was ended, aggressive behavior and time spent interacting with the juvenile were greater in the animals treated chronically with EtOH, regardless of whether they were injected with saline or 0.50 g/kg of EtOH. The results of these studies showed that chronic EtOH treatment can produce long-lasting changes in social behavior after drug treatment is over and can alter the animal's normal response to EtOH in a social setting.     

Prenatal maternal stress: Differential effects upon male and female offspring responses to restraint stress as adults

Pregnant primiparous rats were subjected to four days of light restraint stress on postconception days 7 through 10, inclusive, coincident with the development of the fetal gastrointestinal system. Twenty male and twenty female offspring from prenatally stressed and nonstressed rats were then subjected to two hours of supine cold-restraint as adults. Eighty percent of nonprenatally stressed offspring developed gastric lesions, while 47.5% of offspring of prenatally stressed mothers displayed lesions. A significant sex-stress interaction was detected, indicating that male offspring from prenatally stressed mothers display less severe gastric lesions in response to restraint stress as adults than do male offspring from nonprenatally stressed mothers. Female offspring from both prenatal stress conditions showed similar levels of stress-induced lesions.     

Role of the sympathetic nervous system in cerebrovascular responses to air-jet stress in rats

This study examined the role of sympathetic nerves in the control of cerebral hemodynamics during air-jet stress. In adult male Sprague-Dawley rats, blood flow velocity (pulsed Doppler) was measured in both internal carotid arteries 1 week after excision of one superior cervical ganglion. Blood pressure (BP) and carotid blood flows (CBFs) were simultaneously recorded during exposure to air-jet stress. In 5 out of 13 rats, stress was applied after β(2)-adrenoceptor blockade with ICI 118551 (0.4 mg/kg, then 0.2 mg/kg/h, i.v). Stress evoked an immediate rise in BP, CBFs, and vascular conductances. Vasodilatation was much larger on the denervated side than on the intact side (mean ± SEM: 78 ± 7 versus 19 ± 4%; P < 0.02) and lasted about 10 s. Thereafter, blood flows returned to or near normal and showed parallel variations while BP remained elevated. There was, therefore, a net vasoconstriction on both sides. In ICI 118551-treated rats, the initial vasodilatation was not significantly reduced on the denervated side (64 ± 4%), but the subsequent vasoconstriction was enhanced (P < 0.05) on both sides. In conclusion, air-jet stress evokes an immediate, short-lasting vasodilatation through a mechanism unrelated to β(2)-adrenoceptor stimulation. Sympathetic nerves powerfully limit this phenomenon, and thus contribute to protect the cerebral circulation from stress-induced BP surges.     

Cardiovascular responses to open-field stress in rats: sex differences and effects of gonadal hormones

We studied sex differences in cardiovascular responses to stress using a new radio-telemetry model in which freely-moving Spontaneously Hypertensive rats (SHR) are exposed to open-field novelty stress. This model allowed simultaneous assessment of cardiovascular and behavioural responses to psychological stress. Female SHR in the diestrous stage of their estrous cycle had markedly greater pressor and tachycardic responses to open-field exposure when compared to either female rats not in diestrous or male SHR. Treatment of ovariectomized SHR with estrogen alone had no significant effect on cardiovascular reactivity, while a combined treatment of estrogen and progesterone slightly, but significantly attenuated their pressor response to open-field stress. In addition, treatment of castrated male rats with testosterone significantly enhanced their pressor responses to stress when compared to values obtained before treatment. None of the hormone treatments had any significant effect on heart rate responses to stress. Neither at different stages of the estrous cycle nor after hormone treatments were there any marked changes in behavioural responses in the open-field, making it unlikely that the differences in cardiovascular stress responses were caused by changes in behavioural activity. These data demonstrate differences in cardiovascular stress responses that seem to be dependent on the stage of the estrous cycle. They suggest that particularly androgens, such as testosterone, may enhance pressor responses to stress. On the other hand, a combination of estrogen and progesterone, rather than estrogen alone, may have a small attenuating effect on cardiovascular reactivity.     

Repeated acute stress alters heart morphometry in male and female rats differently

Stress exerts deleterious effects on the cardiovascular system. Left ventricular hypertrophy has been identified as a risk factor for heart disease. The effects of stress on other heart parameters, including heart size and heart shape, are not well-characterized. In addition, the extent to which males and females differ in stress effects on these measures has not been examined, but may help to further explain gender differences in heart disease morbidity and mortality. The present experiment examined effects of mild daily stress on heart morphology and blood volume (obtained by ex-sanguination at decapitation) in 39 male and 40 female rats of two strains. Following 14 days of stress exposure, rats were killed and blood volume was measured. Heart length, heart weight, left ventricle cavity width, right ventricle width, lateral wall thickness, anterior wall thickness, posterior wall thickness, and septal wall thickness were measured. In males, after controlling for body weight, stress decreased heart length and left ventricle cavity width and increased septal wall thickness. In females, after controlling for body weight, stress reduced total blood volume, but did not significantly affect other heart parameters. These findings suggest that stress exposure can alter heart morphology and blood volume and that there are sex differences in these effects.     

Effects of stress on nonassociative learning processes in male and female rats

In this study we assessed habituation and sensitization of the acoustic startle response (ASR) to discern whether intense, inescapable stress affects nonassociative learning differently in male and female rats. Rats were inescapably stressed 2 hours per day over 3 consecutive days. ASR magnitudes were measured at several times post-stress (1, 4, 8, and 15 days after cessation). Females generally showed greater ASR magnitudes (compared to males), but both sexes exhibited short and long-term habituation across the testing days. ASR magnitudes were only affected by stress in male subjects. The effect in males was an increase in short-term sensitization of the ASR on post-stress day-4. The results suggest that stressed males and females react differently to ASR testing, in that stress males appear to develop an exaggerated ASR response over repeated test sessions due to short-term sensitization. The source of the short-term sensitization is discussed with regards to possible stress-induced enhanced contextual learning during ASR testing on post-stress day-1.     

Reduction in paradoxical sleep after L-dopa administration in rats

The EEG and EMG activity of two groups of rats (N = 8 each) was recorded during one experimental and 5 control days. On the experimental day, one group received 125.0 mg/kg L-dopa preceded by 50.0 mg/kg benserazide hydrochloride. The other group received 1.0 mg/kg haloperidol, immediately before the recording session. After L-dopa plus benserazide administration the total time and the number of episodes of paradoxical sleep and slow wave sleep decreased significantly compared to control sessions.     

Brown adipose tissue redox status in response to dietary-induced obesity-associated oxidative stress in male and female rats

Obesity is linked to systemic oxidative stress and, although brown adipose tissue (BAT) plays a crucial role in energy balance, BAT redox status effects on obesity have not been studied previously. Female rats exhibit a greater BAT thermogenic capacity, attributed to enhanced mitochondrial differentiation, than males. The aim of this study was to investigate whether the mitochondrial sexual dimorphism is related to differences in BAT redox status and to assess its role in the regulation of body weight gain in response to chronic high fat diet (HFD) feeding. Ten-week-old Wistar rats of both genders were fed a pelleted control diet or HFD for 26 weeks. Although mitochondria of female rats produced higher levels of hydrogen peroxide than those of males, females exhibited lower oxidative damage, attributed to greater glutathione peroxidase activity and higher glutathione content. In response to HFD, body weight increased markedly in females, but oxidative capacity increased only in males, thus maintaining improved BAT redox status compared with females. In conclusion, the sexual dimorphism in BAT redox status found in control animals is attenuated by the HFD. The enhanced oxidative capacity of HFD males can be related to their greater resistance to body weight gain.     

Integration of cardiac responses to serial stimuli after Pavlovian conditioning in rats

The expression of cardiac responses to sequences of two sounds was studied in restrained rats following discriminative trace or delay conditioning. Stimuli paired with a tail shock 10 sec later (CS1) elicited conditioned bradycardia. Unpaired or neutral stimuli (CS0) elicited mostly tachycardia. Rats did not learn to suppress responding to nonreinforced sequences with an interval of 6 sec between sounds. Responses to the second stimulus were significantly augmented following a CS1 stimulus, but not following a CS0 stimulus. Real-time summation of simple responses provided a more complete and quantitative prediction of dual responses than did resetting or facilitation. These results extend the time range over which summation may be observed from less than 2 sec to at least 16 sec. They appear to be inconsistent with models involving competition between unitary representations of stimuli in short-term memory and suggest the existence of multiple stimulus traces with independent time courses.     

Chronic stress and carbohydrate metabolism: persistent changes and slow return to normalcy in male albino rats

The present study tested the hypothesis that long-term repeated exposure to stressors results in irreversible changes in carbohydrate metabolism. Groups of adult male rats (five per group) were restrained for 1?h and 4?h later were forced to swim for 15?min everyday for 2, 4, or 24 weeks; five rats were autopsied after each interval. Groups of five rats exposed to stress for 2 or 4 weeks were maintained without further treatment (recovery groups) for up to 24 weeks. The fasting blood glucose concentration, measured at weekly intervals, was significantly higher in the stressed rats than in controls throughout the experiment, except in the 24th week, whereas that of the recovery groups was significantly higher than controls only up to the 8th week after the end of stress exposure and then reached normalcy. The blood concentrations of glucose, lactate, and pyruvate were significantly higher in the 2 and 4 weeks stress groups than in controls, whereas, except for lactate, in rats stressed for 24 weeks these values did not significantly differ from those in controls. These changes were accompanied by increased gluconeogenesis and glycogenolysis as shown by alterations in activities of hepatic carbohydrate metabolizing enzymes and unaltered blood insulin concentrations in rats stressed for 2, 4, and 24 weeks. Furthermore, the blood insulin levels did not significantly vary among controls and the 2, 4, and 24 weeks stress groups. The results reveal that though hyperglycemia induced by long-term stress exposure is reversible, it persists for a prolonged period, even after the termination of stress exposure, before reaching normalcy. Prevalence of hyperglycemia for a prolonged period through increased activities of hepatic enzymes in stressed rats exemplifies allostasis.     

Effect of atropine or atenolol on cardiovascular responses to novelty stress in freely-moving rats

Cardiac hemodynamic mechanisms involved in cardiovascular responses to stress were studied in conscious, freely-moving female spontaneously hypertensive rats exposed for 15 min to an open-field. When pretreated with saline, the rats displayed a rapid rise in blood pressure, heart rate, aortic dP/dt and locomotor activity. In rats pretreated with 0.5 mg/kg of methylatropine, the tachycardia was slightly, but significantly reduced. In rats pretreated with 1 mg/kg of atenolol, the tachycardis and rise in dP/dt were markedly reduced. These data suggest that the cardiac responses to stress include predominantly cardiac sympathetic activation and a minor component of vagal withdrawal.     

Enduring deficits in contextual and auditory fear conditioning after adolescent, not adult, social instability stress in male rats

Adolescence is a time of developmental changes and reorganization in the brain and stress systems, thus, adolescents may be more vulnerable than adults to the effects of chronic mild stressors. Most studies, however, have not directly compared stress experienced in adolescence to the same stress experience in adulthood. In the present study, adolescent (n=46) and adult (n=48) male rats underwent 16 days of social instability stress (daily 1h isolation and change of cage partners) or were non-stress controls. Rats were then tested on the strength of acquired contextual and cued fear conditioning, as well as extinction learning, beginning either the day after the stress procedure or 3 weeks later. No difference was found among the groups during the Training Phase of conditioning. Irrespective of the time between the social stress experience and fear conditioning, rats stressed in adolescence had decreased context and cue memory, and cue generalization compared to control rats, as measured by the percentage of time spent freezing in tests. Social instability stress in adulthood had no effect on any measure of fear conditioning. The results support the hypothesis that adolescence is a time of heightened vulnerability to stressors.     

Chronic sildenafil (Viagra) administration reduces anxiety in intact and castrated male rats

Epidemiological research indicates that sildenafil (Viagra) abuse is associated with increased risk behaviors. The present study employs the open field, a standard animal model used in the field of anxiety research, to examine whether chronic exposure to sildenafil affects anxiety and risk-taking behaviors in gonadally intact and castrated male Wistar rats. Sildenafil (10 mg/kg) or saline were administered three times a week for three weeks. Animals were tested once a week in the open field during and after drug treatment. Sildenafil treatment increased the number of center entries and time spent in the center in intact and castrated animals during and after treatment, suggesting that repeated drug use decreases anxiety. Sildenafil also restored the deficits in exploration and locomotion produced by castration, indicating that sildenafil effects on open field behaviors are independent of endogenous androgens. We caution against generalizing from this study to human behaviors, but propose that the behavioral effects produced by a chronic high dose of sildenafil warrant further studies into its abuse potential.     

Electrophysiological responses to ethanol, pentobarbital, and nicotine in mice genetically selected for differential sensitivity to ethanol

Cortical electroencephalographic (EEG) changes induced by ethanol (4.3 and 1.4 g/kg, ip), pentobarbital (50 and 16 mg/kg), and nicotine (1.0 g/kg) were examined in long-sleep (LS) and short-sleep (SS) mice that were genetically selected for differential sleep times induced by a hypnotic dosage of ethanol. Ethanol (4.3 g/kg) caused EEG changes that paralleled the behavioral differences, whereas no differences between selected lines were observed following the activating dose (1.4 g/kg). Data support the notion that the known difference in ethanol sleep times is due not to greater SS sensitivity to ethanol activation but rather to greater LS sensitivity to ethanol hypnosis. No differences between selected lines were observed following 50 mg/kg pentobarbital, which again parallels previous behavioral data. The SS mice were more responsive to pentobarbital activation (16 mg/kg). Nicotine more severely reduced EEG power and heart rate in LS mice; a continuous iv infusion of nicotine elicited a distinct pattern of behavioral stereotypy for each selected line, with more profound motor and reflex depression in LS mice. The lines do not differ in rate of nicotine metabolism, hence they must differ in central nervous system sensitivity to nicotine. Thus, lines of mice selectively bred for differential sensitivity to ethanol also display marked differences in electrophysiological and behavioral responses to nicotine.