Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats

Summary Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (³H-diazepam- and³H-imipramine-binding sites) have revelaed, however, less consistent intrapair differences.     

Genetic and environmental influences on reactive and spontaneous locomotor activities in rats

Paired groups of rats (derived from divergent, selective breeding or living in divergent environmental conditions) were compared with regard to locomotor activities. Intrapair differences were found to vary non-systematically, depending upon whether the rats were initially exposed to a test-environment with or without a slight environmental modification (reactive activities), or were allowed to habituate extensively to the environment (spontaneous activity). Since the behavioral patterns were found to represent distinct entities, this pointed to the necessity of differentiating clearly between spontaneous and reactive activities and indicated, once again, that both genetic and environmental influences are important in these behaviors and must be taken into account. Accepting and controlling for these variables makes it possible to use the factor of individual differences in laboratory animal behavior to advantage.     

Genetic and environmental influences on reactive and spontaneous locomotor activities in rats

Paired groups of rats (derived from divergent, selective breeding or living in divergent environmental conditions) were compared with regard to locomotor activities. Intrapair differences were found to vary non-systematically, depending upon whether the rats were initially exposed to a test-environment with or without a slight environmental modification (reactive activities), or were allowed to habituate extensively to the environment (spontaneous activity). Since the behavioral patterns were found to represent distinct entities, this pointed to the necessity of differentiating clearly between spontaneous and reactive activities and indicated, once again, that both genetic and environmental influences are important in these behaviors and must be taken into account. Accepting and controlling for these variables makes it possible to use the factor of individual differences in laboratory animal behavior to advantage.     

Genetic and histological aspects of stomach lesions induced by systemic injection of phenylbutazone in the rat

Roman high-avoidance (RHA/Verh) rats, food-deprived (F-D) for 5 days, had higher stomach lesion scores than did F-D Roman low-avoidance (RLA/Verh) rats. F-D RLA/Verh rats which were injected i.p. with phenylbutazone (PBZ) 24 h before examination, however, had higher scores than did PBZ-treated, F-D RHA/Verh rats. Histologically, extensive edema and cellular infiltration (including numerous erythrocytes) were seen below the lesions, in the submucosa, denoting vascular damage. An attenuating influence of food on the ulcerogenic effects of PBZ, which were much more severe in F-D than in fed rats, was also indicated.     

Genetic and histological aspects of stomach lesions induced by systemic injection of phenylbutazone in the rat

Summary Roman high-avoidance (RHA/Verh) rats, food-deprived (F-D) for 5 days, had higher stomach lesion scores than did F-D Roman low-avoidance (RLA/Verh) rats. F-D RLA/Verh rats which were injected i.p. with phenylbutazone (PBZ) 24 h before examination, however, had higher scores than did PBZ-treated, F-D RHA/-Verh rats. Histologically, extensive edema and cellular infiltration (including numerous erythrocytes) were seen below lesions, in the submucosa, denoting vascular damage. An attenuating influence of food on the ulcerogenic effects of PBZ, which were much more severe in F-D than in fed rats was also indicated.The authors thank K. Bättig and J. R. Martin for their assistance during the planning stages, B. Hauser, A. Waldvogel and P. Wild of the Veterinary Medical Faculty of Zurich University for preparing the histological sections and for the photography, and P. Elsinger for technical help.     

Glykogenbildung nach Thymektomie

Summary (1) No differences were found in the glycogen contents in liver, heart, and various other muscles between thymectomized and normal rats.(2) There are likewise no differences in glycogen synthesis in the diaphragm in the presence of glucose, alone and with insulin, between thymectomized and normal rats.(3) The weight of adrenal glands, absolute as well as in relation to the body-weight, shows no difference too between thymectomized and normal rats.     

3H-Diazepam binding sites in Roman high- and low-avoidance rats

The binding of 3H-diazepam to membrane benzodiazepine receptors was examined in 2 psychogenetically selected lines of rats, which differ according to the selection criterion in avoidance behaviour (RHA/Verh greater than RLA/Verh) and, in addition, in emotionality (RHA/Verh less than RLA/Verh). RHA/Verh rats tended to show higher specific diazepam binding in all CNS-subregions when compared with RLA/Verh animals. Significant differences were found in the cortex, striatum, hippocampus, thalamic region and pons-medulla. These results reinforce the contention that a system involving benzodiazepine receptors may play a role in emotional behaviour.     

Bone marrow in male and female rats

Summary Sex differences of high significance in the marrow weight relative to femur volume, as well as to body weight, were found in adult rats. A positive significant correlation was found between the femur volume and the marrow volume in both sexes, while a negative significant correlation between femur density and the marrow content (mg/mm³) exists only in male rats.     

Maternal behavior in two rat lines selected for differences in the acquisition of two-way avoidance.

The maternal behavior of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats was studied, using a time-sampling method. It was concluded that: a)RLA/Verh mothers spent more time with their young, b) RHA/Verh mothers were more active, and c) the mothers of both lines mostly "blanketed' their young during nursing, although the RHA/Verh mothers assumed the side-nursing position more often than their counterparts.     

Impaired insulin release in aging rats: Metabolic and ionic events

We investigated the effect of aging on glucose uptake, glucose-induced O₂ consumption, glucose-induced⁴⁵Ca movements, and calmodulin content to elucidate age-related impairment of glucose-induced insulin release in pancreatic islets of Wistar rats. Intact pancreatic islets from old (24-month-old) rats showed impaired glucose-induced insulin release; glucose uptake and O₂ consumption were lower in old than in young (2-month-old) or adult (12-month-old) rats. Moreover,⁴⁵Ca uptake and calmodulin content were decreased in pancreatic islets from older rats, which explained the impairment in glucose-induced insulin release in aging. No major differences between the 3 age groups in glucose-induced⁴⁵Ca efflux in pancreatic islets were observed.     

Genetic determinants of individual differences in avoidance learning: Behavioral and endocrine characteristics

Bidirectional genetic selection for good and poor active avoidance learning in a shuttle box has been carried out in three independent laboratories using remarkably similar discrete-trial training procedures. The resulting strains are known as the Roman High and Low Avoidance (RHA and RLA), the Syracuse High and Low Avoidance (SHA and SLA) and the Australian High and Low Avoidance (AHA and ALA) strains, respectively. An additional unidirectionally selected strain, known as the Tokai High Avoider (THA) strain was developed in Japan using a free-operant Sidman avoidance procedure in a Skinner box. This paper reviews the selection of the Syracuse strains, enumerates the various behavioral and endocrine characteristics of the strains, and compares them to the other similarly selected strains. The behavioral work suggests that genetic selection from diverse breeding stocks has resulted in common characteristics that differentiate the strains in the emotional, not learning, domain. The endocrine data, however, are somewhat at odds. The Syracuse strains differentiate one way with respect to endocrine function, and the Roman strains differentiate in the opposite way. We suggest, therefore, that the endocrine correlates are not tightly linked to the avoidance genotype. Genetic analysis of all of the selected strains for both the avoidance phenotype and the endocrine correlates will be needed to test this hypothesis.Preparation of this paper was supported by research grant MH-39230-3 from the National Institute of Mental Health.     

Maternal stress alters monoamine metabolites in fetal and neonatal rat brain

Heat-restraint stress given rats during the last week of gestation significantly altered dopaminergic dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA) and noradrenergic 3-methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG) forebrain-hypothalamic monoamine (MA) metabolites in female offspring. On gestational day 21, HVA and MOPEG were significantly higher and lower, and on postnatal day 1 all were higher. There were virtually no differences in brain MA concentrations in males. Thus MA metabolic concentrations differ in fetal-neonatal forebrain-hypothalamus as a function of sex differences and maternal stress.     

Maternal stress alters monoamine metabolites in fetal and neonatal rat brain

Summary Heat-restraint stress given rats during the last week of gestation significantly altered dopaminergic dihydroxyphenylacetic acid and homovanillic acid (DOPAC and HVA) and noradrenergic 3-methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG) forebrain-hypothalamic monoamine (MA) metabolites in female offspring. On gestational day 21, HVA and MOPEG were significantly higher and lower, and on postnatal day 1 all were higher. There were virtually no differences in brain MA concentrations in males. Thus MA metabolic concentrations differ in fetal-neonatal forebrain-hypothalamus as a function of sex differences and maternal stress.     

Structures and strategies in ancient Greek and Roman technical writing: An Introduction

Most of our knowledge of Greek and Roman scientific practice and its place in ancient culture is derived from our study of ancient texts. In the last few decades, this written evidence—ancient technical or specialist literature—has begun to be studied using tools of literary analysis to help answer questions about, for instance, how these works were composed, their authors’ intentions and the expectations of their readers.This introduction to Structures and strategies in ancient Greek and Roman technical writing provides an overview of recent scholarship in the area, and the difficulty in pinning down what ‘technical/specialist literature’ might mean in an ancient context, since Greek and Roman authors communicated scientific knowledge using a wide variety of styles and forms of text (e.g. poetry, dialogues, letters).An outline of the three sections is provided: Form as a mirror of method, in which Sabine Föllinger and Alexander Mueller explore ways in which the structures of texts by Aristotle and Plutarch may reflect methodological concerns; Authors and their implied readers, with contributions by Oliver Stoll, David Creese, Boris Dunsch and Paula Olmos, which examines what ancient texts can tell us about the place of technical knowledge in antiquity; Science and the uses of poetry, with articles by Jochen Althoff, Michael Coxhead and Laurence Totelin, and a new English translation of the Aetna poem by Harry Hine, which explores the (to us) unexpected roles of poetry in ancient scientific culture.     

Inhibition of cholesterol synthesis ex vivo and in vivo by fluvastatin,a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase

The inhibitory effect of fluvastatin sodium (fluvastatin), a new type of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A inhibitor, on de novo cholesterol synthesis was investigated and compared with that of pravastatin. Fluvastatin at a concentration of 12.5 mg/kg inhibited sterol synthesis ex vivo from [¹⁴C]acetate in rat liver and ileum by 97–99% with respect to the control, while the inhibition in kidney was 55%. The inhibition by fluvastatin in the liver and ileum persisted for approximately 9 h after administration. Significant differences between fluvastatin also had an inhibitory effect on cholesterol synthesis in vivo in various tissues of rats given [¹⁴C]acetate intraperitoneally. Sterol synthesis in the liver, ileum and kidney was inhibited by over 95% 3 h after administration of 6.25 mg/kg of fluvastatin. Significant differences between fluvastatin and pravastatin were found in the liver and ileum. Fluvastatin was more potent than pravastatin in inhibiting both ex vivo and in vivo sterol synthesis in the ileum (but not in kidney) and liver.     

Characterization of D-fructose transport by rat kidney brush-border membrane vesicles: changes in hypertensive rats

D-fructose transport was characterized in renal brush-border membrane vesicles (BBMVs) from both spontaneously hypertensive rats (SHR) and normotensive genetic control Wistar-Kyoto (WKY) rats. Kinetic studies indicated that the maximal rate (Vmax) of D-fructose transport was significantly lower in SHR compared with WKY rats. No differences were observed in the Michaelis constant (Km) or the diffusion constant (Kd) between the two groups of animals. D-fructose inhibited its own transport, whereas the presence of D-glucose, D-galactose, phlorizin, and cytochalasin B did not inhibit the transport of D-fructose in either animal group. To explain the reduction in D-fructose transport in SHR, the density of the D-fructose transporter, GLUT5, was analyzed by Western blot. GLUT5 levels were lower in SHR, a reduction similar to that of the Vmax. Thus, there appears to be a high-affinity, low-capacity, GLUT5-type fructose carrier in the apical membranes of rat kidney cortex, and the decrease in the Vmax of D-fructose transport in renal BBMVs from hypertensive rats correlates well with a reduction in the expression of GLUT5 protein.     

The behavior of the homozygous and heterozygous sub-types of rats which are genetically-selected for diabetes insipidus: A comparison with Long Evans and Wistar stocks

Several aspects of spontaneous and conditioned behavior (food and water intake, locomotion and emotionality, passive and active avoidance acquisition and retention) of standard (albino and pigmented) rats, and rats heterozygous (HEDI) and homozygous (HODI) for diabetes insipidus, are reviewed. As would be expected, HODI rats have been repeatedly found to consume far more fluid than either HEDI or control rats. Pigmented rats appear to be more active than albinos. HODI rats exhibit less marked emotional responses than do control rats, among which the pigmented ones exhibit the highest emotionality. Light aversion is more evident in albino than in pigmented rats. No differences are found among HEDI, HODI and normal Long Evans rats. It is quite difficult to provide a clear-cut statement concerning inter-strain differences in passive avoidance behavior, possibly because of the variety of techniques employed. In any case, HODI rats do not perform worse than normal controls do. In one-way active avoidance paradigms, pigmented rats perform better than albinos, and the performance of HODI rats does not differ from that of controls. In two-way avoidance paradigms, albinos appear to outperform pigmented rats. Once again, there are no obvious differences between HODI and control animals.In addition to indicating that HODI rats may actually be less emotional than the other groups of rats reviewed here, the studies described once again fail to confirm the previously alleged functions of vasopressin in memory consolidation.     

Maternal behavior in two rat lines selected for differences in the acquisition of two-way avoidance

Summary The maternal behavior of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats was studied, using a time-sampling method. It was concluded that: a) RLA/Verh mothers spent more time with their young, b) RHA/Verh mothers were more active, and c) the mothers of both lines mostly blanketed their young during nursing, although the RHA/Verh mothers assumed the side-nursing position more often than their counterparts.This work was partly supported by a research grant from the Swiss Association of Cigarette Manufacturers. Reprint reqyests should be addressed to P. Driscoll at the given address.     

Serotonergic and cholinergic interaction in the regulation of pituitary-adrenal function in rats

It has been proposed that the central serotonergic inputs which modulate pituitary-adrenal secretion are mediated by cholinergic neurons. We have tested this hypothesis in intact rats. Male Sprague-Dawley rats were injected with cholinergic and serotonergic agents which enhanced transmitter function and with receptor blocking agents. Agents were injected, singly and in combination, into both unstressed and stressed animals. Since the response to cholinergic agents might be due to changes to vasopressin release, Brattleboro (vasopressin deficient) rats were also injected with cholinergic agents. The level of plasma corticosterone at 1-h post-injection was determined. Results indicate that the serotonin receptor blockade decreased the stimulatory, cholinergic effect of physostigmine. Cholinergic receptor blockers did not significantly reduce the corticosterone rise induced by 5-hydroxytryptophan. These results do not support the hypothesis of cholinergic mediation of serotonergic input. Nicotinic and muscarinic receptors appeared to exert opposing influences on the system. The nicotinic receptor antagonist was able to block the stimulatory effect of physostigmine. The muscarinic receptor antagonist significantly elevated plasma corticosterone levels. No differences were found in the effect of physostigmine on Brattleboro rats as compared to controls. These data are interpreted as suggesting that 1) the acetylcholine-induced stimulation of pituitary-adrenal function is mediated, in part, by serotonergic neurons; and 2) stimulation of nicotinic receptors is facilitatory whereas stimulation of muscarinic receptors is inhibitory to pituitary-adrenal function.     

Renal effects of a high unsaturated fat diet in renal artery stenosis in rats

The renal effects of an unsaturated fat (UNSAT) diet in mild to moderate two-kidney, one-clip (2K1C) renovascular hypertension were evaluated. An UNSAT diet (37% by energy) prevented the development of hypertension compared to 2K1C rats fed a high saturated fat (SAT) (37% by energy) and a normal fat (CONTROL) (11% by energy) diet. Urinary sodium and fractional sodium excretion increased in 2K1C rats as compared to SHAM operated controls, regardless of the diet received. In the early weeks of the experiment (weeks 2–4 post-surgery to induce hypertension), an enhanced natriuresis occurred in the 2K1C UNSAT as compared to the 2K1C CONTROL and SAT diet groups. This resulted from an increase in the glomerular filtration rate (GFR in mls·min^–1) as measured using the single-injection [⁵¹Cr] EDTA method (2K1C UNSAT; 1.99±0.18 versus 2K1C SAT; 1.27±0.09, p<0.02; and versus SHAM CONTROL; 1.45×0.01; p<0.02). The increased GFR was not associated with alterations in effective renal plasma flow (ERPF) as measured using the single-injection [¹²⁵I] Na hippurate method. No differences in sodium excretion; GFR; ERPF or renal blood flow (microsphere technique) were noted between the 2K1C UNSAT and SAT diet groups at weeks 6–8 post-surgery, despite a continued antihypertensive effect of the UNSAT diet. Hence, the antihypertensive effect of an unsaturated fat diet in 2K1C renovascular hypertension in rats is associated with transient glomerular changes leading to an enhanced natriuresis.