Dudley F. Peeler

Genetic factors and the measurement of exploratory activity

The progenitor strains C57BL/6 and BALB/c and the seven recombinant inbred strains derived from them were used to examine the genetic relationship between two measures of activity and hippocampal lamination defect (Hld). Fifty-three mice (Mus musculus), 9 from each of the progenitor strains and 5 from each recombinant inbred strain, were tested for 16 min in a device which permitted both unobstructed traverse of the length of a runaway and contact with objects which were aligned alongside the runway. The C57BL/6 mice produced significantly more locomotor (runway traversal) activity, whereas the BALB/c showed significantly greater amounts of investigatory (object contact) activity. This reversal of relative position in the distribution of scores was not present for the recombinant strains. There was no dichotomous separation of recombinant strains for either measure. Examination of activity in terms of four consecutive 4-min periods indicates differences among the strains with respect to changes during the test session. The strains may be dichotomized with respect to decrement in activity within the 16-min session, but these groups do not correspond with those reported by others. The inference of a single genetic determinant for activity measured either as locomotor or investigatory responses is not supported by these data, nor is there any apparent relationship between activity and Hld. The critical influence of genetic-environment interactions in determining behavior and the effect of the selection of measurement techniques upon interpretation of data are emphasized by these data.

Active avoidance performance in genetically defined mice

It has been concluded by several investigators that active avoidance performance in mice is primarily influenced or even determined by a single gene. The genetically defined strains C57BL/6 and BALB/c have provided evidence that an aberrant development of pyramidal cells and mossy fiber configuration in the hippocampus of BALB/c mice also is determined by a single gene. As a test of the generality of the single gene influence on avoidance learning, and to examine the relationship of the hippocampal defect to avoidance learning, adult male mice of the inbred progenitor strains C57BL/6ByJ and BALB/cByJ and their seven recombinant inbred strains were tested in a variant of the shuttle-box paradigm used in previous studies. BALB/c were found to acquire the avoidance response at a faster rate than C57BL/6, consistent with most earlier reports, but performances of the recombinant inbred strains failed to dichotomize about the progenitor strains. The rank order of performance scores for the recombinant inbred strains was different from that reported in previous studies. Thus the present data failed to support the interpretation of a single major gene influencing active avoidance learning. It is concluded that avoidance learning and performance cannot be considered as unitary variables and that the interaction of genetic with environmental factors, including the conditions of the specific testing situation, are important considerations in any interpretation of genetic effects. No relationship between the hippocampal lamination defect and avoidance performance was demonstrated.

Effect of septal lesions on response to frustrative nonreward

Abstract Male albino rats, septal-lesioned and control, were subjected to frustrative nonreward in the Amsel double runway. Results revealed that the magnitude of the frustration effect with both running and starting speed measures was not affected by septal lesions. This finding was interpreted as supporting McClearys inhibitory-deficit hypothesis of septal lesion effects.

Two measures of activity in genetically defined mice as a function of strain, time of day, and previous experience

Genetically defined adult mice from progenitor strains C57BL/6 and BALB/c and the 7 recombinant inbred strains derived from them were tested at one of five times of day for amount of locomotor and investigatory activity in three 16-min sessions. Strain, sex, time of day, and experiential factors are shown to interact in variable and complex fashion. Previous reports of a single major gene’s determining activity level are contradicted. Observed genetically determined differences were not in concordance with strain distribution patterns for other genetically determined traits. Interpretation of locomotor and investigatory activity as separable behaviors is supported. Habituation (activity decrement) both within and between sessions is added to the behaviors amenable to behavior genetic investigations.

Shuttlebox performance in BALB/cByJ, C57BL/6ByJ, and CXB recombinant inbred mice: Environmental and genetic determinants and constraints

Male mice from nine strains (the CXB recombinant inbred set and their progenitors, BALB/cByJ and C57BL/6ByJ) were tested in a shuttlebox for two-way avoidance acquisition in an effort to resolve discrepancies between earlier studies. Mice were tested at one of three times of day (TOD) using one of three apparatus configurations. Analysis of variance revealed complex interactions between strain, apparatus configuration, and TOD. Subsequent analyses and tests of simple effects indicated very strong influences of apparatus configuration and/or TOD upon rate of acquisition in some strains, but not in others. C57BL/6 mice were relatively little affected by either variable; BALB/c mice were responsive to apparatus configuration but not to TOD. The recombinant inbred strains performed variously at levels that were either intermediate to, comparable with, or higher than those of the progenitors, depending upon the context of the testing situation. Genetic determination of behavior is, in part, a function of the particular context in which the behavior occurs. Both TOD and apparatus configuration are significant environmental factors.

Response rate for food and water in the rat as a function of noncontingent, reinforcing septal stimulation

Rats with electrodes in the septal region of the brain received noncontingent, reinforcing stimulation while bar pressing for food and for water on variable ratio schedules. Rate of pressing for water was found to be significantly reduced as a function of intracranial stimulation. No significant differences were found between stimulation and nonstimulation periods for Ss reinforced with food. The data revealed no change in general activity as a function of the electrical stimulation.

Effects of haloperidol on motor and cognitive functioning in aged mice

The effects of haloperidol on motor and functioning and cognitive functioning were studied in young (3-5 months old) and aged (20-22 months old) male mice by examining haloperidol-induced catalepsy and haloperidol-induced decrements in performance on a radial arm maze. The aged mice were much more sensitive to these adverse effects of haloperidol than were the young mice. Studies of the distribution of radioactivity from [3H]haloperidol to the brain indicated that the differences in sensitivity to this drug were not due to pharmacokinetic differences. The results demonstrate that mice are suitable for studies of aging-induced changes in the behavioral effects of neuroleptic agents.

Non-adrenergic exploratory behavior induced by moxonidine at mildly hypotensive doses.

Moxonidine is a centrally-active imidazoline compound with preferential affinity for imidazoline receptors (IR) over alpha(2)-adrenoceptors (alpha(2)AR). Clinically, moxonidine has proven advantageous for treating hypertension over pure alpha(2)-adrenergic agonists (i.e., guanabenz) due to its lowered incidence of sedative side effects. The present experiments reveal divergent behavioral effects of low doses of moxonidine and guanabenz in C57Bl/6 mice in an exploratory arena. Low-dose moxonidine (0.05 mg kg(-1) i.p.) elicited an increase in novel object contacts (+36%) and more movement into central space (+56%; P<0.01) compared to saline-injected controls; whereas guanabenz induced only dose-responsive sedative-like behaviors in the same paradigm. Yet, the two agonists were indistinguishable in terms of blood pressure changes over a similar dose range (0.025-0.1 mg kg(-1) i.p.) in consciously free-moving mice (Delta mean+/-S.E.M.=-12.3+/-3.2 mm Hg for moxonidine versus -13.5+/-1.9 mm Hg for guanabenz). As expected of alpha(2)AR involvement, the sedative-like effects of guanabenz were completely blocked by pretreatment with the non-imidazoline alpha(2)AR-antagonist, SKF86466 (0.5 or 1.0 mg kg(-1) i.p.). However, the pro-exploratory effects of low doses of moxonidine (0.05 or 0.1 mg kg(-1)) were not antagonized by SKF86466. These results suggest that moxonidine acts preferentially through a non-adrenergic mechanism, possibly IR-mediated, to elicit pro-exploratory behavior.

Magnesium pemoline: Effect on food reinforced discrimination performance in rats

Rats injected with magnesium pemoline reached acquisition criterion in a visual discrimination task with significantly fewer reinforced trials than control Ss. However, on retention tests given four and six weeks later, control Ss performed significantly better than drug Ss. The results suggest that magnesium pemoline enhances stimulus responsiveness and motor activity rather than directly affecting central learning processes.