Nelson Adams

The Maudsley Reactive and Nonreactive Strains: A New Perspective

Research on the Maudsley Reactive and Maudsley Nonreactive strains conducted primarily between 1980 and 2001 is reviewed. One line of research, which has found consistent differences between the Harrington derivation of the Maudsley Reactive (MR/Har) and Maudsley Nonreactive (MNRA/Har) strains in conflict situations, appears to support the traditional view of the two strains as representing models of global differences in emotionality. In contrast, comparisons of the two strains in two commonly used tests that involve a component of fear either do not reveal differences between the strains (escape-avoidance conditioning) or are inconsistent in expression (elevated plus maze). Emphasis is placed on the importance of recognizing that most of the phenotypic differences discovered among selected inbred strains, including the Maudsleys, will inevitably be unrelated to the original selection criterion, but that many of these phenotypic differences will have their own intrinsic interest. For example, the fact that, relative to MNRA/Har, two bottle ethanol preference is greater in MR/Har rats and that MR/Har rats exhibit greater exploration of novel stimuli when these are presented in a familiar environment may have little to do with the hypothesized differences in emotionality among the strains. It is suggested the MR/Har drinking pattern in alcohol preference tests, which is characterized by considerable variability, may complement other models of alcoholism, especially in the investigation of environmental influences which contribute to the variability. In the case of strain differences in response to novelty, this may help explain some of the inconsistencies in findings in the elevated plus maze, which, aside from provoking fear, also contains an important element of novelty. Finally, it has been found that alterations in the peripheral sympathetic nervous system (PSNS) are correlated with strain differences in open-field defecation (OFD) in the Maudsley model, and it has been proposed that the lower OFD of MNRA/Har rats is a direct result of sympathetic inhibition of colonic motility. These strain differences in the PSNS are furthermore associated with important alterations in the response of the central noradrenergic system to acute and chronic stress. It is hypothesized that genes may have influenced PSNS tone by altering CNS structures with descending projections. If the link between low levels of OFD and higher peripheral sympathetic tone is supported by additional experiments, this will force reconsideration of OFD as an index of emotionality.

Development of dominance in domestic rats in laboratory and seminatural environments.

Dominance hierarchies were studied in mixed-sex colonies of albino rats Rattus norvegicus reared and housed in three different types of physical environments. Colonies were observed. In either an outdoor pen, an indoor pen, or in laboratory cases for a period of 24 weeks initiated at 35 days of age. In both pen colonies, male dominance relationships were based on the asymmetric display of biting attacks by dominants and the unequivocal display of submissive postures by subordinates. These behaviours did not fully develop, nor did dominance emerge until males were 140-150 days of age. No asymmetric display of attacks and submission, nor dominance relationships were observed in two different types of laboratory cage settings; these males continued to play fight throughout adulthood. However, males of all colony types attacked male intruders. The nature of the physical environment appeared to have a powerful influence on the development of dominance, but did not affect agonistic behaviour directed toward intruders.

Sex differences and the effects of tail pinch on ethanol drinking in Maudsley rats

Voluntary consumption of 10% ethanol (EtOH) vs. water was compared in EtOH-naive, male and female Maudsley Reactive (MR) inbred rats that were exposed to either daily episodes of tail pinch (TP), or no-stress controls for 35 consecutive days. Females drank significantly more EtOH than males as measured by preference for 10% EtOH vs. water, and for intake of pure EtOH. Females exposed to TP had a higher preference for EtOH relative to controls after 21 days, but there was no difference over the entire 35 days. Males exposed to TP tended to drink more EtOH during the last week of testing relative to controls. Experiment 2 compared MR females with Maudsley Nonreactive (MNRA) females for 3 weeks in the conditions described above; TP exposure increased EtOH preference in MR, but not in MNRA, females. MR females also consumed significantly more EtOH than MNRA females. In both experiments female rats drank amounts of EtOH following a 6-week period of EtOH abstinence comparable to their preabstinence levels. The large degree of variability found in inbred MR rats has implications for developing a model for the investigation of environmental influences on the development of EtOH abuse in genetically susceptible individuals.

Genetic influences on digging behaviors in mice (mus musculus) in laboratory and seminatural settings.

Digging behaviors of several inbred strains of laboratory mice and some of their crosses were examined in three contexts. In laboratory burrow boxes, C57BL/6Abg mice constructed more sophisticated burrow systems than did BALB/cAbg mice. Their F1 hybrids built burrow systems more complex than either parental strain. The same pattern of genetic influence was observed in an outdoor pen. In an escape task that required digging, BALB/c mice escaped more quickly than did C57BL/6 mice; their F1 hybrids showed dominance toward the BALB/c phenotype. These results indicate that behavioral polymorphisms in digging behavior, which may relate to habitat selection, have a genetic basis. The dominance and overdominance toward the better digging parental strain in each type of task suggest the possible evolutionary importance of these digging behaviors.

Mouse (Mus) burrows: Effects of age, strain, and domestication

Burrows dug by house mice in laboratory burrow boxes were examined in two inbred strains (C57BL/6J and BALB/cJ) across five age groups and compared with burrows of wild trapped mice. Burrows of feral domestic mice were examined in an outdoor enclosure as well as in the laboratory. Results demonstrated that burrows differ between strains; highly active C57 mice tended to burrow more than did Balbs at all age ranges. Moreover, burrows became more complex with age in both strains. Differences among domestic, feral, and wild mice were minimal. Results are discussed in terms of possible genetic differences in activity and as evidence against the notions of degeneracy accompanying domestication.

Contrasting effects of social stress and foot-shock on acute cardiovascular response in salt-sensitive rats.

Repeated defeat by an aggressive resident attacker rat produces a large decrement in systolic blood pressure (SBP) in male S/JR rats. The present experiments compared the cardiovascular (CV) response of male S/JR rats exposed either to repeated defeat, or to a common laboratory stressor, electric foot-shock. Using the tail-cuff method of determining SBP, the results of Experiment 1 replicated the previous finding that on the second and subsequent exposures, repeated defeat is followed by an acute decrement in SBP (30-40 mm Hg in magnitude). In contrast, repeated exposures to foot-shock were followed by acute increases in SBP (20-40 mm Hg) and in heart rate (HR). In Experiment 2, mean arterial blood pressure (MAP) and HR were measured directly from chronically cannulated male S/JR rats after defeat or exposure to foot-shock: again, defeated males exhibited an acute decrease in MAP, whereas the MAP of rats exposed to foot-shock tended to increase. In Experiment 3 we varied the parameters of shock intensity and the social context of shock exposure. Male S/JR rats exposed to more intense foot-shock than in the previous experiments or to foot-shock while paired with one of the resident attacker rats all exhibited acute increases in SBP. The results of these experiments indicate that CV response to defeat may be qualitatively different from CV response to foot-shock.

The Effect of a High Salt Diet and Gender on Blood Pressure, Urinary Protein Excretion and Renal Pathology in Shr Rats

A high salt diet produced increases in SBP, urinary protein excretion (UPE) and renal vascular lesions (RVL) across groups of male and female SHR rats which were allowed to develop moderate or excessive increases in SBP. A highly significant linear relationship between SBP and log-transformed UPE was found when the data from all groups were analyzed together. Males developed high blood-pressure more rapidly, and exhibited more severe RVL and greater UPE than females. Two results prevent the conclusion that the elevated UPE was simply due to the adverse effects of high BP on the kidney. First, the relationship between SBP and UPE across groups could not be demonstrated when regression analyses were performed within individual dietary sub-groups. Secondly, gender differences in UPE were highly significant by analysis of covariance adjusting for individual differences in SBP. The increases in SBP and UPE may be independent consequences of ingestion of a high salt diet.

Effects of social defeat on acute cardiovascular response in salt-sensitive and salt-resistant rats

We studied the effects of social stress (SS) and a high salt diet on systolic blood pressure (SBP) and heart rate (HR): S/JR male rats (which exhibit marked elevations in SBP when placed on a high sodium diet) and R/JR male rats (which are resistant to the BP-elevating effects of a high sodium diet) were maintained on a low sodium diet (0.3% NaCl) or placed on a high sodium diet (8% NaCl). Within each dietary condition independent groups were either exposed to SS, by placement in the cage of a trained fighter male (Long-Evans breed) for 25 min, or exposed to no stress. The dietary regimen was imposed for 10 days with stress exposures on Days 1, 2, 3, 5, 7, and 9, with SBP and HR measured indirectly by tail plethysmography 3 min following exposure to SS. SS produced an acute decrease in SBP (20-30 mm Hg) in S/JR rats on the second and subsequent exposures, but did not affect HR. SS did not affect SBP of R/JR rats, but did produce a significant elevation of HR. Maintenance on the high sodium diet increased SBP in S/JR, but not R/JR, rats when it was measured on the eighth (no stress) day, but SS obscured the effects of diet on SBP on days when rats were stressed. Following exposure to attacks, defeated SS rats displayed an upright submissive posture relatively late during the first stress exposure when no change in SBP was observed after SS in S/JRs, but displayed the submissive posture immediately and with long duration on the second and subsequent exposures when a marked decrement in SBP was seen.

Outdoor enclosures for feralizing rats and mice

Rationales for the naturalistic study of rattus and mus in outdoor enclosures are well known but rarely transformed into practice. This paper describes the materials, construction details, and operational procedures for rat and mouse pens that are easily and inexpensively built and maintained. The suggestion here is that outdoor enclosures offer meaningful views of rodent behavior not accessible in traditional laboratory situations.

Maternal influences on cardiovascular pathophysiology

Elevated blood pressure (BP) is of special clinical significance because of its association with pathophysiologies such as heart disease, renal failure, and stroke. We described the development of a protocol for use with hypertensive rats in which prepubertal exposure to a high salt (8% NaCl) diet results in a pathophysiological syndrome including rapid increase in BP, failure to maintain normal weight gain, renal damage, cerebrovascular lesions, and early mortality. These phenomena are described for the inbred spontaneously hypertensive rat (SHR), and for reciprocal F1 hybrids of a cross between SHR and the Dahl salt-sensitive (SS/Jr) inbred strain. The study with reciprocal F1s revealed striking effects of maternal environment on pathophysiological response to a high salt diet. F1s nurtured by SHR mothers weighed less at 35 days of age, and after exposure to the high salt diet suffered more rapid BP increases, greater incidence of stroke, body weight loss, and mortality, than F1s nurtured by SS/Jr dams. These results suggest that maternal mediation of the nutritional status of the animal may play an important role in determining susceptibility to elevated BP and subsequent pathophysiology associated with exposure to a high salt diet. The implication of these findings for human hypertension is briefly discussed.