Cardiac beta-receptor variation in rat strains selectively bred for differences in susceptibility to stress

The radioligand 3H-DHA was used to estimate the density and affinity of cardiac beta-receptors in rat strains selectively bred for differences in response to stress. Maudsley Reactive rats selected for heightened reactivity to stress had a greater density of beta-adrenergic binding in cardiac membranes than rats of two genetically distinct Maudsley Non-Reactive strains selected for decreased reactivity to stress, and compared with one of these Non-Reactive strains the MNR/Har, increased affinity for 3H-DHA. Together with previous findings the present results demonstrate a negative correlation between estimates of basal sympathetic activity on the on hand, and post-synaptic beta-receptors in heart on the other, that are consistent with the notion that these receptor alterations have occurred as a result of long-term differences in pre-synaptic release of transmitter. The Maudsley strains may, therefore, provide a useful model for the study of beta-adrenergic receptors as a physiological locus for regulation of end-target responsiveness to sympathetic stimulation.     

Features of the stress reaction in rats with genetically-determined emotionality (from EEG indicators)]

The features of the EEG spatial organization in two rat strains, i.e., with expressed emotional reactions (Maudsley reactive, MR) and less reactive (Maudsley nonreactive, MNR) were compared in two stress situations: during exposure to the action of pain (P) (i.p. injection of 0.9% NaCl solution) and during 24-hour water deprivation (D). Multichannel EEG recording (24 derivations) and their multiparametric estimation (840 signs) made it possible to differentiate characteristic features of the EEG spatial organization in rats with initially increased emotional reactions and passive behavioral strategy during exposure to stress. In both stress-inducing conditions, an increase in crosscorrelation and coherence between cortical potentials in parallel with rise of the spectral power in the range of high-frequency theta and its drop in the range of EEG high-frequency band was observed in the MR rats. The MNR rats showed the opposite changes. Different reactivity of the ratio between the coherence and spectral power of potentials was observed in two strains of rats. This index characterizes the level of the information-energy component of the spatial organization of cortical potentials. It is suggested that different character of the EEG changes reflects the features of interhemispheric relations, information-energy processes, and cortical regulation of autonomic processes in the system of adaptive stress reactions at different levels of emotionality and behavioral strategy.     

Spatial organization of EEG in rats with genetically determined emotionality

In order to study the possibility of EEG discrimination of genetically determined emotionality (increased propensity to emotional and stress reactions and anxiety) brain electrical activity was recorded in rats of two strains: Maudsley Reactive and Maudsley Nonreactive (24 derivations from the convexital skull surface were used). The program package "Synchro-EEG" was used for EEG processing. It was demonstrated that the two rat strains were significantly different in 120 EEG parameters of 840 ones analyzed. On the basis of 37 parameters, each rat was correctly recognized as belonging to the respective group with the error of 4.89%. The analysis of the detected signs allowed their classification to be performed in accordance with the peculiarities of the emotional and cognitive processes and the level of nonspecific activation. Specific forms of interaction between these components in the system of emotional reactions were revealed.     

Differences in central noradrenergic and behavioural responses of Maudsley non-reactive and Maudsley reactive inbred rats on exposure to an aversive novel environment

The present experiments compared the noradrenaline and behavioural responses of inbred Maudsley reactive (MR) and non-reactive (MNRA) rats when they are exposed to the light or dark arena of a light/dark shuttle-box. Behavioural scores confirmed that both strains of rats perceived the light arena to be more aversive than the dark one. Using in vivo microdialysis, exposure to the light, but not the dark, arena was found to increase noradrenaline efflux in both the frontal cortex and the hypothalamus of MNRA and MR rats. However, whereas the increase in the frontal cortex of both strains and the hypothalamus of MR rats was transient, the hypothalamic response in MNRA rats was maintained throughout exposure to the test zone. Strain differences in activity/visit and time/visit were evident but it was not possible to discern whether this could be attributed to the strain difference in the hypothalamic noradrenaline response. Nevertheless, it remains possible that, by comparison with MR rats, the prolonged noradrenaline response in the hypothalamus of MNRA rats could contribute to their well-documented, greater resistance to aversive environmental stimuli.     

Measurements of brain amobarbital concentrations in rats anesthetized and overdosed by amobarbital and treated centrally with dibutyryl cyclic AMP.

Three doses of amobarbital, an anesthetic dose (80 mg/kg), a minimum lethal dose (130 mg/kg), and a high lethal dose (180 mg/ kg) were administered intraperitoneally to groups of rats. All rats were injected intracerebroventricularly with 0.9% saline or dibutyryl cyclic AMP, 200 μg/rat. While those rats treated with saline solution were still sleeping at decapitation and those treated with dibutyryl cyclic AMP were awake, there were no significant differences in their brain concentrations of amobarbital.     

Effects of stress and chronic propranolol infusion on cardiac beta-receptor function in the Maudsley Reactive and Non-Reactive rat strains

The effects of beta-adrenoceptor blockade on left ventricular beta-receptor characteristics were evaluated in the Maudsley Reactive (MR/Har) and Non-Reactive (MNRA/Har) rat strains. After propranolol infusion for one week administered by subcutaneously implanted osmotic minipumps, differences in beta-adrenoceptor-agonist interactions between strains were assessed by comparison of isoproterenol competition for [125I]iodocyanopindolol (ICYP) binding sites in crude left ventricular homogenate preparations from both strains. Propranolol exposure had no significant effect on the binding parameters investigated (Bmax, Kd, % receptors in high affinity state, IC50). In contrast to previous observations in naive animals, these experiments revealed no strain differences in the sham-implanted Maudsleys in any of the left ventricular beta-adrenoceptor parameters investigated. We hypothesize that the surgical procedures and/or presence of the plastic inserts acted as stressors in the Maudsley strains and thus altered beta-adrenoceptor function. This hypothesis is supported by the observation that exposure to another stress (footshock) also eliminated strain differences in ventricular beta-receptor binding variables.     

EEG study of the anxiolytic effect of scopolamine

Effect of the central M-cholinolytic scopolamine on spatial organization of the rat brain electrical activity was studied under conditions of high and low emotional-stress responses. The EEG changes were estimated by 840 parameters. A possibility of the EEG discrimination by means of interstrain differences in responses to scopolamine, was shown. A more obvious decrease in spectral power and potentials coherence was revealed in Maudsley Reactive rats (MR) as compared with the Maudsley Nonreactive rats (MNRA), in parieto-temporal and occipital areas of the right hemisphere, and the reverse interrelationship occurred in the anterior parts of the right and posterior parts of the left hemisphere. These findings suggest some specifics in the spatial distribution of the maximum scopolamine action foci depending on the initial emotional level. Changes occurring under the scopolamine effect in different EEG frequency bands are different in the MR and the MNRA rats. The findings are discussed in respect to the EEG indices of anxiolytic component of cholinergic regulation of the brain activity.     

Inhibition of γ-aminobutyric acid release from rat cerebral cortex slices by barbiturate anesthesia

Amobarbital and pentobarbital anesthesia inhibited the potassium-stimulated, Ca-dependent release of -aminobutyric acid (GABA) from rat cerebral cortex slices during incubation in vitro. Inhibition of GABA release was not found when slices were prepared from rats shortly after they awakened from amobarbital anesthesia. Phenobarbital anesthesia did not affect the release of GABA.     

Vitamin A-deficiency and thyrotropin secretion in the rat.

Basal serum TSH concentrations and TRH-induced TSH response were studied in control and in vitamin A-deficient rats at different times between the fifth week on diet (when growth of deficient animals was still normal) and the beginning of the weight plateau (as soon as growth of deficient animals had stopped). In deficient rats the TSH values were always lower than in the control rats. TRH injections (50 ng/100 g b.w.) in anaesthetized animals (amobarbital 1 mg/100 g b.w.) resulted in an approximately 12-fold increase in serum TSH levels within 6 minutes. The TSH levels remained elevated for at least 15 minutes and were similar in control and deficient rats. We hypothesize that the lower basal serum TSH concentrations are the result of a feedback mechanism triggered by an increase of serum free thyroxine (FT4) and free triiodothyronine (FT3).     

Biological sexual maturation in rats: Interaction among genetic line,sex, age,and body weight

Interaction among genetic line, sex, age and body weight was studied for biological sexual maturation in rats. In female rats vaginal opening, first estrus, and duration of estrus cycle were determined. In male rats first presence of sperm was determined. Age and body weight at vaginal opening, first estrus or first detection of sperm were determined. Differences among five genetic lines were found on all measures of sexual maturation. The random bred control rats differed from the selectively bred lines of rats on majority of the measures, thus suggesting the influence of selective breeding on sexual maturation. The Maudsley lines selected for open-field defecation and Roman lines selected for two-way active avoidance learning showed different patterns of sexual maturation. Age was found to be crucial for the sexual maturation of female rats, whereas body weight was more important for the sexual maturation of male rats. This study is the first to investigate systematically the biological sexual maturation in live male rats and related sex differences. Findings suggest an important genetic component, and effect of selective breeding on the biological sexual maturation of rats.     

Ventilatory phenotypes among four strains of adult rats.

Our purpose in this study was to identify different ventilatory phenotypes among four different strains of rats. We examined 114 rats from three in-house, inbred strains and one outbred strain: Brown Norway (BN; n = 26), Dahl salt-sensitive (n = 24), Fawn-hooded Hypertensive (FHH: n = 27), and outbred Sprague-Dawley rats (SD; n = 37). We measured eupneic (room air) breathing and the ventilatory responses to hypoxia (12% O(2)-88% N(2)), hypercapnia (7% CO(2)), and two levels of submaximal exercise. Primary strain differences were between BN and the other strains. BN rats had a relatively attenuated ventilatory response to CO(2) (P < 0.001), an accentuated ventilatory response to exercise (P < 0.05), and an accentuated ventilatory roll-off during hypoxia (P < 0.05). Ventilation during hypoxia was lower than other strains, but hyperventilation during hypoxia was equal to the other strains (P > 0.05), indicating that the metabolic rate during hypoxia decreased more in BN rats than in other strains. Another strain difference was in the frequency and timing components of augmented breaths, where FHH rats frequently differed from the other strains, and the BN rats had the longest expiratory time of the augmented breaths (probably secondary to the blunted CO(2) sensitivity). These strain differences not only provide insight into physiological mechanisms but also indicate traits (such as CO(2) sensitivity) that are genetically regulated. Finally, the data establish a foundation for physiological genomic studies aimed at elucidating the genetics of these ventilatory control mechanisms.     

Circadian Rhythm of Outside-Nest Activity in Wild (WWCPS), Albino and Pigmented Laboratory Rats

The domestication process of the laboratory rat has been going on for several hundred generations in stable environmental conditions, which may have affected their physiological and behavioural functions, including their circadian system. Rats tested in our ethological experiments were laboratory-bred wild Norway rats (WWCPS), two strains of pigmented laboratory rats (Brown Norway and Long Evans), and two strains of albino rats (Sprague-Dawley and Wistar). Rats were placed in purpose-built enclosures and their cycle of activity (time spent actively outside the nest) has been studied for one week in standard light conditions and for the next one in round-the-clock darkness. The analysis of circadian pattern of outside-nest activity revealed differences between wild, pigmented laboratory, and albino laboratory strains. During daytime, albino rats showed lower activity than pigmented rats, greater decrease in activity when the light was turned on and greater increase in activity when the light was switched off, than pigmented rats. Moreover albino rats presented higher activity during the night than wild rats. The magnitude of the change in activity between daytime and nighttime was also more pronounced in albino rats. Additionaly, they slept outside the nest more often during the night than during the day. These results can be interpreted in accordance with the proposition that intense light is an aversive stimulus for albino rats, due to lack of pigment in their iris and choroid, which reduces their ability to adapt to light. Pigmented laboratory rats were more active during lights on, not only in comparison to the albino, but also to the wild rats. Since the difference seems to be independent of light intensity, it is likely to be a result of the domestication process. Cosinor analysis revealed a high rhythmicity of circadian cycles in all groups.     

Vasopressin deficiency and circadian rhythms during food-restriction stress

Vasopressin-containing, Long-Evans (LE) rats and vasopressin-deficient, Brattleboro (DI) rats were monitored for activity and core body temperature via telemetry. Rats were exposed to a 12-12 light-dark cycle and allowed to habituate with ad lib access to food and water. The habituation period was followed by an experimental period of 23 h of food-restriction stress in which a 1-h feeding period was provided during the light cycle. Although both strains of animals showed nocturnal activity and temperature rhythms during the habituation period, DI rats were more active than LE rats. The DI rats also had a lower body temperature in the dark. During the experimental period, both strains exhibited a phase shift of activity and body temperature correlating with the presentation of food. The DI rats developed a diurnal shift more rapidly than LE rats. The DI animals showed a dramatic increase in activity during the light phase and a marked decrease in body temperature during the dark phase. The LE animals showed a significant attenuation of activity, but maintained both nocturnal and diurnal temperature peaks throughout the food-restricted condition.     

Acute stress increases plasma concentrations of atrial natriuretic peptides

5 min exposure of inbred Maudsley Reactive male rats to intermittent foot-shock resulted in an approximate doubling of plasma atrial natriuretic peptides ANP (Control grp mean = 62.12 +/- 8.74; Stressed grp mean = 128.70 +/- 26.63 pg/ml) and 25 min exposure resulted in a three-fold increase (Stressed grp mean = 187.88 +/- 39.24 pg/ml). In the second experiment exposure of genetically heterogeneous Wistar male rats to 15 min of intermittent foot-shock produced a 10-fold increase in plasma ANP (Control grp mean = 45.76 +/- 6.05; Stressed grp mean = 471.20 +/- 58.49 pg/ml). The magnitude of the increase in plasma ANP produced by acute stress is as large as the increase caused by volume expansion and administration of various pharmacological agents and therefore delineation of biological role of ANP must take account of its potential role as a stress-hormone.     

Developmental Patterns of Catechol-O-Methyltransferase in Genetically Different Rat Strains: Enzymatic and Immunochemical Studies

Abstract: Catechol- O -methyltransferase (COMT) activity in the liver and kidneys of adult Fischer-344 (F-344) rats is only half of that in the same organs of Wistar-Furth (W-F) rats. The trait of low COMT activity in these animals is inherited in an autosomal recessive fashion. A comprehensive study of patterns of change in COMT activity during growth and development was performed to determine whether "temporal gene" effects might play a role in the inherited differences in enzyme activity present in adult animals. The COMT activity expressed per mg protein in liver and kidneys of newborn F-344 rats is only 50–60% of that in the same organs of W-F animals. The liver and the kidneys of newborn rats of both strains have COMT activity an order of magnitude higher than those in brain, heart, or blood. In addition, in both strains there are much larger increases in liver and kidney COMT activities during growth and development (5–10 fold) than in blood, brain, or heart (one- to twofold). Immunotitration with antibodies against rat COMT demonstrates that differences in immunoreactive COMT parallel differences in COMT activity, both between strains and within strains during growth and development. However, when the temporal patterns of change in enzyme activities in the liver and the kidneys of the two strains of rat are compared at multiple times during growth and development, no differences in the patterns are present. These results make it unlikely that temporal gene effects can explain the inherited differences in COMT activity in liver and kidneys of F-344 and W-F rats.     

The effect of nicotine and alcohol on the fertility and life span of rats. A cytological analysis

Inbred Fisher and Buffalo rats were exposed to nicotine and alcohol. Fertility was greatly reduced in both strains with nicotine treatments being much more deleterious than alcohol use. Fisher rats tolerated both toxins better than Buffalo rats. Both strains became 'extinct' after one generation of fetal and postnatal exposure to nicotine, but alcohol-ingesting Fisher rats had 3 or more generations of offspring. The total reproductive period was significantly shortened in both strains under the effect of both toxins, as was the total life span. The causes of the teratological effects of both toxins are inflammatory processes as evidenced by the presence of numerous lymphocytes and/or polymorphonuclear leukocytes. Their presence occurs earlier in nicotine than in alcohol use and earlier in Buffalo than in Fisher rats, but the damage done during nicotine treatment is reversible when the procedure is terminated. Inflammation is not transmitted to the newborn offspring of nicotine- or alcohol-treated mothers, but occurs in neonates during the nursing period or later. There is considerable individual variation in the tolerance to both toxins. Experimental results and clinical observations show a sufficient number of similarities to justify the use of experimental data as a model for further studies on human subjects.     

Study on the optimum number of trials and intensity of unconditioned stimulants and strain difference in the two-way shuttle-box avoidance test using rats

In order to determine the optimun conditions suitable for a number of trials and the intensity of unconditioned stimulant (US) in the two-way shuttle-box avoidance test in Sprague-Dawley strain rats, which are used most frequently in reproduction studies, conditioned avoidance response was observed under various conditions for 30 and 60 trials and the low and high US levels. Investigation was also conducted in Wistar rats under a high US level with 30 and 60 trials. Latency time of the escape response in Sprague-Dawley rats was shortened with increasing trials. Body weight gains of both strains of rats in the high US level with the 60-trial group decreased during the observation period. These findings suggest that the high US level with the 60-trial group is not suitable for the two-way shuttle-box avoidance test. The rate and latency time of the avoidance response were lower in Wistar rats than in Sprague-Dawley rats, although those of the escape response were higher. Significant changes in the following were observed, mainly from first to third sessions: the avoidance rate of all groups in strains of rats, escape rate of 60-trial group in Sprague-Dawley rats, avoidance and escape latency time of the 60-trial groups in both strains of rats and escape latency time of the 30-trial group in Sprague-Dawley strain rats.     

Plasmodium berghei: Phagocytic activity in two strains of rats

The Wistar and Sprague-Dawley strains of rats differ in their ability to maintain phagocytic hyperactivity toward colloidal carbon during infection with Plasmodium berghei. Both strains were highly stimulated by the 4th day, but on the 7th and 8th days of infection one-third of the Sprague-Dawley rats were not hyperactive while all the Wistar rats remained hyperactive. The course of infection subsequent to the carbon test was similar in hyperactive and in nonhyperactive rats.     

Barbiturate-induced Disorientation of Root and Shoot Geotropism in Germinating Cruciferous Seedlings

Cruciferous seedlings germinated on glass-distilled water andon barbital manifested normal root and shoot geotropisms whereastwisted roots and shoots were evident in seedlings germinatedon amobarbital and secobarbital, the roots often being completelysuspended in the air. The marked difference in germination anddevelopment behaviour of cress and white mustard seedlings germinatedon barbital compared with that on amobarbital and secobarbitalindicate that the Meyer-Overton principle of drug potency andlipid solubility was operative in both species of germinatingseedlings. Lepidium sativum L., Sinapsis alba L., seed germination, geotropism, barbiturates     

Typological features of behavior and memory in Norway rats selected for absence of aggression toward a man

Features of behavior and retrieval of passive conditioned avoidance on a new and forgotten stimuli were compared in Wistar rats and Norway rats bred for the absence of aggression toward a man. As distinct from white rats, grey rats were characterized by low anxiety and high locomotor exploratory activity in the elevated plus maze and dark-light chamber. Norway rats demonstrated better avoidance performance with active defensive behavioral strategy than Wistar rats. Latent inhibition during conditioning with a previously forgotten situational stimulus was the same in both rat strains. The results are discussed in terms of the use of grey rats as a model for an in-depth analysis of the mechanisms of memory optimization.