David A. Blizard

Sex differences in open-field behavior in the rat: The inductive and activational role of gonadal hormones ☆

Abstract Male rats are generally found to be significantly less active and to defecate more than female rats in the open-field test. In developmental studies, these differences were shown to emerge in the peripuberal period at 50–60 days of age. After gonadectomy in adult life, the sex difference in open-field activity was reduced in magnitude but did persist indicating that it was not solely dependent on the presence of gonadal secretions in either sex. In contrast, the sex difference in open-field defecation did not reach statistical significance after gonadectomy with ovariectomized females exhibiting increased defecation frequency. Estrogen-progesterone replacement stimulated activity and decreased defecation scores to pre-gonadectomy levels in females but lacked effect in males. Administration of testosterone propionate (TP) to female rats in neonatal life produced developmental changes in open-field behavior similar to those seen in the male. In addition, the response of TP treated females to gonadectomy and hormone replacement was similar to that found for the male. These results suggest that the presence of testosterone in neonatal life plays a role in the masculinisation of open-field behavior and that its effect is partly mediated by the presence of cyclic ovarian secretions in the adult female rat and their absence in the male and TP treated female.

Genetic correlation between open-field activity and defecation: analysis with the cxb recombinant-inbred strains.

Confirming previous investigations involving descendants of C57BL/6J and BALB/cJ mouse strains, significant phenotypic, environmental, and genetic correlations (r=−0.53, −0.24, −0.92, respectively) were found between open-field activity and defecation in recombinant-inbred strains descended from a cross of C57BL/6By and BALB/cBy strains. These correlations were found to be dependent on the level of illumination in the open-field test. They were statistically significant in a brightly illuminated open field but statistically insignificant in a dimly illuminated test situation.

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-alpha-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 alpha-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.

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.

Blood pressure, heart rate, and plasma catecholamines under resting conditions in rat strains selectively bred for differences in response to stress.

Maudsley Reactive and Maudsley Nonreactive rats exhibited clear differences in basal physiological function. Under resting conditions, Maudsley Reactive rats had higher systolic and diastolic blood pressure and heart rate and exhibited lower basal plasma NE levels than Nonreactive rats. These results and previous observations suggest that genetic selection for differences in behavioral reactivity has produced fundamental alterations of autonomic function with clear involvement of the sympathetic system. The finding that the strains differ in basal autonomic function as well as in autonomic reactivity suggests that both “basal” and “reactive” dimensions must be considered in attempting a satisfactory explanation of differences in physiological and behavioral response in the Maudsley strains.

Amelioration of an age-related deficit in exploratory behavior by preexposure to the test environment.

Aged (28-month-old) C57BL/6N Nia mice spent significantly less time exploring a novel stimulus than 4- or 8-month-old mice. The lower level of exploratory behavior in 28-month-old mice was independent of age differences in locomotor activity and the detection of a novel stimulus. Prior exposure to the test apparatus, without the novel stimulus present, produced a significant enhancement of the exploratory behavior in 28-month-old mice and attenuated age differences in exploratory behavior. It is suggested that the reduced exploratory behavior of 28-month-old mice is due to their greater reactivity to the novel stimulus.

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 organisms response to stress. Strain differences in hypothalamic DA function may play a role in the etiology of strain differences in serum Prl.

PLASMA CATECHOLAMINES UNDER BASAL AND STRESSFUL CONDITIONS IN RAT STRAINS SELECTIVELY BRED FOR DIFFERENCES IN RESPONSE TO STRESS

Under basal conditions, Maudsley Reactive (MR) rats had lower plasma norepinephrine (NE) levels than Maudsley Non-Reactive (MNR) rats. Following open-field (OF), handling (H) and immobilization (I) stressors, MR rats exhibited significant increases in plasma NE, but MNR rats showed no significant change from basal NE levels. Plasma epinephrine (E) levels did not differ under basal conditions in the two strains, but the increases in plasma E following stress were larger and more consistent in MR compared with MNR animals. These results suggest that the differential susceptibility of the two strains to stressful stimuli indicated by their marked differences in behavioral and autonomic response in stressful situations may be related to differences in the function of their noradrenergic system under basal conditions.

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.

Head mount for the control of infusion in freely moving animals

The construction of a light weight head mount for the control of infusion in small laboratory animals is described. The head mount reduces restraint of the animal and includes a valve to seal the cannula so that the animal may be disconnected from the infusion system.