Maudsley Reactive Research Articles

“Peripheral” benzodiazepine binding sites in the maudsley reactive rat: Selective decrease confined to peripheral tissues

“Peripheral” benzodiazepine binding sites (PBS) were studied in both the CNS and peripheral tissues of Maudsley reactive (MR) and Maudsley non-reactive (MNR) rats using the PBS specific ligand [ 3H]Ro 5-4864. A statistically significant reduction in the density of PBS was found in heart and kidney of the MR compared to the MNR. Similar reductions in the density of PBS were not observed in a number of areas of the central nervous system (including cortex, hippocampus, and hypothalamus) or other peripheral tissues, such as lung and adrenal. This selective decrease in PBS in a strain selectively bred for a high degree of “fearfulness” may be related to previous findings of a reduction in the density of PBS in the same tissues in rats subjected to uncontrollable shock. These observations suggest that PBS in heart and kidney may be altered in response to fear or anxiety.

Open-field behavior and the peripheral sympathetic nervous system in the MR/N and MNR/N rat strains.

The Maudsley Reactive (MR) and Maudsley Non-Reactive (MNR) strains of rats, respectively selected by P. L. Broadhurst for high and low open-field defecation (OFD), were acquired by the National Institutes of Health in 1963 at the 21st generation of inbreeding and have been inbred as the MR/N and MNR/N strains at that location for more than 40 generations. The present experiment shows that, despite the lack of deliberate selection for more than 40 generations, the strains still differ predictably in OFD. Strain differences in open-field activity, originally found to be inversely associated with those in OFD, have also been preserved. The existence of an association between the peripheral sympathetic system and OFD originally established in the Har derivation of the Maudsley strains was also confirmed in the MR/N and MNR/N strains: MR/N male rats, with the relatively higher levels of OFD, exhibited lower concentrations of norepinephrine (NE) in spleen and descending colon than MNR/N rats. The pattern of biochemical and morphological findings obtained in this study and previous data indicate that the MNR/N and the MNR/Har strains are both derived from the British stocks of this strain carrying the agouti allele (AA). A distinction should be made between these strains and the MNRA/Har strain, which carries the nonagouti allele (aa) and which has been genetically isolated from the Nonreactive strains bearing the agouti allele since early in the selection experiment.

Emotional correlates of selection for avoidance learning in rats

The Roman high-avoidance (RHA) and low-avoidance (RLA) strains of rats were tested and compared with Maudsley reactive (MR) and non-reactive (MNR) strains to assess the relative contributions of emotionality and conditionability to differences between the two Roman strains. The RHA learned significantly faster in active avoidance, but slightly slower in passive avoidance, significantly faster in acquisition of an active approach task, but slightly slower in extinction of active approach tasks despite extensive adaptation and gentling. The RHA showed more ‘rearing’, more activity in the open field and more variety-seeking. Crossing with MNR showed the RHA less reactive in the open field. Results show RLA equivocal in conditionability, more emotional, and perhaps less active.

Central serotonergic function and behavior in the Maudsley reactive and nonreactive strains: a reevaluation.

Confirming earlier research, Maudsley Reactive (MR) male rats had higher concentrations of serotonin (5-hydroxytryptamine) in brain stem than did Maudsley Nonreactive (MNR) rats. Comparisons of MR with a second MNR substrain (MNRA) revealed no strain differences in brain stem serotonin. The two MNR substrains exhibit similar levels of open-field defecation, and both differ substantially from MR animals. The present results suggest that, contrary to previous claims, brain stem serotonin is not consistently related to open-field defecation in the Maudsley strains.

GENETIC ANALYSIS OF THE MIXED LYMPHOCYTE REACTION IN H‐1 SEROLOGICALLY IDENTICAL INBRED RATS

SUMMARYH‐1d and H‐11 serologically identical combinations of inbred rat strains were studied, in which there was a strong mixed lymphocyte reaction (MLR). The H‐1d identical combination was formed with the Maudsley reactive (MR) and BD IX strains, in which there was bidirectional stimulation. The LAD differences in the combination BD IX and MR were shown in experiments using back‐crosses derived from two different sources, BD IX x LEW and MR x LEW.The H‐11 identical combination was the F344 (Fisher) and LEW (Lewis) strains; here the MLR was unidirectional—LEW stimulating F344. Two other H‐11 serologically identical strains, AS and HCS, also stimulated F344 lymphocytes. Genetic segregation analyses using back‐crosses showed linkage with H‐1 in both instances. The LADs of AS, HCS and LEW appeared to be the same.These experiments show that the rat LADs so far detectable using these strains are all encoded by genes linked to the major histocompatibility system of the rat, despite serological identity. In addition to disassociation of the major histocompatibility system antigens detected by serological means and those defined by MLC testing, there was also disassociation of transplantation antigens as shown in the BD IX x MR model.

Central and peripheral norepinephrine concentrations in rat strains selectively bred for differences in response to stress: Confirmation and extension

Inbred rats from the Maudsley Reactive (MR) strain had lower concentrations of norepinephrine in hypothalamus, heart, and spleen, and lower total catecholamines in adrenal than inbred Maudsley Non-Reactive rats (MNRA line). In contrast, they had a higher concentration of telencephalic NE than MNRA rats. These results confirmed previous findings obtained on rats maintained by non-systematic breeding within the two lines. Comparisons were also made between MR and a second Maudsley Non-Reactive strain (MNR). Rats of the two Non-Reactive lines (MNRA, MNR) have been bred from the same foundation population and selected for the same behavioral characteristics, but have been genetically isolated from each other for many generations. It was found that MR rats showed differences from MNR rats in hypothalamic and peripheral (but not telencephalic) NE concentrations similar to those seen in MR/MNRA comparisons. Since rats of the two Non-Reactive lines differ appreciably from MR rats in open-field defecation (the criterion on which they were selected), their differences from MR rats in a neurochemical system involved in sympathetic function suggests that this system may be functionally related to well established behavioral and physiological differences between the lines.

Central and peripheral norepinephrine metabolism in rat strains selectively bred for differences in response to stress

Rats of the Maudsley nonreactive (MNRA) strain were found to contain higher levels of norepinephrine in heart, spleen, and hypothalamus than animals of the Maudsley reactive (MR) strain. Total adrenal catecholamines were also greater in nonreactive animals. There was a trend toward higher endogenous norepinephrine concentration in MR rats in brainstem and telencephalon, but this was not statistically significant. Turnover measurements calculated from the fall of norepinephrine at 1 and 4 hours after a single dose of levo-α-methylparatyrosine showed no significant strain differences in telencephalon or brainstem, but MNRA animals had a faster rate of norepinephrine decline in heart than had MR rats. Possibly indicative of a higher rate of norepinephrine metabolism, the percentage of 3H-non-catechol metabolites relative to total counts was higher in brainstem of MNRA rats 90 min after intraventricular injection of 3H-norepinephrine. However, the disagreement between this estimate of norepinephrine metabolism and that provided by the α-methyl-paratyrosine technique prevents a conclusive statement about norepinephrine metabolism in the two strains. The results are discussed in the light of the established differences in behavior between the strains as well as other work exploring relationships between catecholamine metabolism and emotionality.

Serum prolactin and hypothalamic dopamine in rat strains selectively bred for differences in susceptibility to stress.

Rat strains selectively bred for behavioral differences in susceptibility to mild stress exhibited differences in serum prolactin (Prl) and hypothalamic dopamine (DA). Male rats from the Maudsley Reactive (MR) strain had higher levels of serum Prl and hypothalamic DA than rats from the Maudsley Non-Reactive (MNRA) strain. MR rats also showed a greater percentage increase in serum Prl 1 h after blockade of catecholamine synthesis by administration of alpha-methylparatyrosine (alphaMpT). The correlation of basal serum Prl levels with individual susceptibility to stress constitutes further evidence that Prl may play a functional role in the organism's response to stress. Strain differences in hypothalamic DA function may play a role in the etiology of strain differences in serum Prl.

A reevaluation of the relation between estrogen and emotionality in female rats.

It has been hypothesized that the emotionality of the female rat is reduced at estrus. In confirmation of previous research, it was found that administration of estradiol benzoate (EB;20 mug/kg) to female rats of the Maudsley Reactive (MR) strain increased open-field activity and decreased open-field defecation. In addition, ovariectomy increased open-field defecation in MR females. Supporting the generality of these findings, hormone administration reduced open-field defecation and increased open-field activity in intact females of a genetically heterogeneous background. Additional studies suggested that the decrease in open-field defecation at estrus is dependent on estrogenic suppression of food intake. Hormone replacement decreased food intake in the period preceding the open-field test, and colonic contents were also lower in rats treated with EB+P (progesterone) immediately after the completion of the open-field test. These changes were seen in both MR and genetically heterogeneous females. It was concluded that the decrease in open-field defecation at estrus may be mediated by a reduction in food intake and a consequent decrease in colonic contents and that the validity of the defecation response as a measure of emotionality may be seriously questioned under these circumstances.

Effects of early handling on avoidance performance of Maudsley MR and MNR strains.

AbstractThis study investigated the effect of infantile handling on the emotionality and avoidance performance of the Maudsley reactive (MR) and nonreactive (MNR) strains of rats. The expected difference in emotionality was found (MR's had higher defecation scores than MNR's); however, this difference was unaffected by early handling. The avoidance behavior of the 2 strains was different in that MR's had shorter escape latencies; however, they did not differ with respect to CAR's. Handling had a significant effect on avoidance behavior, but this was not greater in one strain than another. The interaction of genetic differences and infantile stimulation on avoidance performance does not appear to be supported in females from these 2 strains.

The Maudsley strains: The evaluation of a possible artifact

Two experiments were carried out on the 31st and 32nd inbred generations of the Maudsley Reactive (MR) and Nonreactive (MNR) strains of rats to assess the contribution of the normal content of their digestive tract to their scores in the open-field test. It was found that the MR strain defecates a significantly greater weight of feces per 24 h than the MNR strain. The MNR strain, however, excretes a greater number of fecal boluses in the same period. Digestive transit time was then measured in the two strains. No differences emerged on this measure. The results together suggest that the differences in open-field defecation between the strains are the result of differential reactivity, rather than reflecting differences in the amount of fecal material in the rectum.

AMOUNT OF OPEN-FIELD DEFECATION, HOME CAGE DEFECATION AND FOOD AND WATER INTAKE IN MAUDSLEY REACTIVE AND NONREACTIVE STRAINS OF RATS

AMOUNT OF OPEN-FIELD DEFECATION, HOME CAGE DEFECATION AND FOOD AND WATER INTAKE IN MAUDSLEY REACTIVE AND NONREACTIVE STRAINS OF RATS

Behavioural correlates of the oestrous cycle in the rat.

CHANGES in certain behavioral functions including learning and exploratory behavior during the oestrous cycle of the intact rat have been reported1,2. Gray and Levine3 recently re-opened the question of the extent to which sex differences in such essentially non-sexual behavior could be determined by the altered behavior of females during oestrus (heat). They induced oestrus in rats of the Maudsley reactive (MR) and non-reactive (MNR) strains by injections of oestrogen and progesterone and observed that emotionality as defined by emotional elimination and ambulatory activity in the open-field test was reduced. Our purpose is to repeat this work using natural as opposed to induced oestrus and to extend it both by the use of other inbred strains and measures of learning as well as emotionality.