Basil E. Eleftheriou

Exploratory activity: Genetic analysis of its modification by scopolamine and amphetamine.

Abstract Short-term exploratory activity was found to be significantly higher in C57BL/6By than in BALB/cBy inbred mice. Scopolamine reversed the activity levels in these strains. Basal exploratory activity levels and the effects of scopolamine on this behavioral measure assessed in these two strains, their reciprocal F 1 hybrids, their recombinant inbred strains and three C57BL/6 congenic lines permitted characterization of a gene exerting a major effect on short-term exploratory activity [ Exa , linked to H(w26), chromosome 4 (LG VIII)] and of a gene modulating the effects of scopolamine in this behavior, [ Sco , linked to H -2, chromosome 17 (LG IX)]. Amphetamine exerted opposite effects in relation to those exerted by scopolamine on activity and its action was found to be determined by a polygenic system.

Morphine sensitivity and tolerance: a genetic investigation in the mouse.

Sensitivity and tolerance to morphine were determined in 2 strains of mice, BALB/cBy and C57BL/6By, their reciprocal F1 hybrids and seven of their recombinant inbred strains. Sensitivity was established based on locomotor activity following the administration of saline, 10 or 20 mg/kg of morphine hydrochloride while tolerance was established according to the “hot plate” method following the single or repeated administration of saline, 5, 10, or 20 mg/kg of morphine hydrochloride. Results indicate that both sensitivity and tolerance to morphine are genotype-dependent and their inheritance is characterized by dominance or partical dominance. Further clarification of the genetic relationship of sensitivity, tolerance and analgesia to morphine must await analysis of the brain morphine-binding protein currently being conducted.

Motor activity and alcohol: genetic analysis in the mouse.

Abstract A genetic analysis of alcohol-induced modification of basal activity level was conducted in two strains of inbred mice, their reciprocal F 1 hybrids, and seven of their recombinant inbred (RI) strains. Alcohol induced a progressive and persistent decline in basal activity level in all of the 11 strains examined. However, the degree and extent of decline in activity varied significantly with particular progenitor or RI strains. Based on this distinct response of the various strains, a strain distribution pattern (SDP) was obtained, followed by testing of congenic line, B6.C- H -16 c . Results of the latter testing indicated that alcohol modification of basal activity is controlled by at least one locus designated Eam (ethanol activity modifier) with Eam h designating the high decrement in activity and similar to the C57BL/6By progenitor, and Eam 1 designating the low decrement in activity and similar to the BALB/cBy progenitor. The locus is found on chromosome 4 (LG VIII) adjacent to the Exa locus which exerts a major influence on basal exploratory activity.

Morphine analgesia in mice of different ages

The analgesic response to 5 mg per kg morphine sulfate was examined in male C57BL/6J mice aged from 2 months to 28 months by the tail-flick assay. The baseline latency of old mice was slightly lower than that of young mice. There was a smaller increase in latency after morphine in old mice than in young mice. Decreased analgesic response in old mice was accompanied by a slower rate of uptake of labeled morphine into the blood after i.p. injection and a longer half-life of the drug. There was no difference between young and old mice in the number of narcotic receptors in the brain.

Chlorpromazine and avoidance: a genetic analysis.

Chlorpromazine exerts a significantly higher impairment on the performance of C57BL/6By than on BALB/cBy inbred mice pretrained in an active avoidance task. The effects of the drug on this measure assessed in these two strains, their reciprocal F1 hybrids, their recombinant inbred strains, and two C57BL/6By congenic lines indicate that at least two genes modulate the action of chlorpromazine on avoidance behavior. It was possible to characterize one of the loci modulating the effect of chlorpromazine on avoidance performance. We assign the symbol Cpz. The locus is in chromosome 9, Linkage Group II.

Reversal learning and RNA labeling in neurological mutant mice and normal littermates.

Abstract Incorporation of radioactive uridine into five brain areas, following reversal learning, was explored for neurological mutant mice with a deficit of myelin in the brain and spinal cord (quaking, qk qk ) and normal littermates (?/+) from strain C57BL/6- qk (Jackson Laboratory). Both groups mastered the reversal task, although the mutants performed at a lower level. There was a Genotype × Test Conditions × Brain Area interaction with littermates exhibiting increased labeling of RNA in the amygdala and the hippocampus, and the quaking mice exhibiting no significant changes in these two areas following learning. Findings suggest that a genetic defect in the integrity of the CNS, a deficiency of myelin, affects reversal learning, and that this effect may be reflected in changes in RNA synthesis, or specific activity, for structures which are critical to reversal learning ability.

Recombinant Inbred Strains: A Novel Genetic Approach for Psychopharmacogeneticists

Historically, species variation in drug responses was one of the primary pharmacological phenomena noted by various investigators dealing with drug responses. Extensive research was conducted into the responses of various species of animals to an identical drug. Thus, it was noticed early in the area of comparative pharmacology that all stimulant agents did not uniformly stimulate, all depressant agents did not uniformly depress and all analgesics did not uniformly induce analgesia in all species examined.

Effects of amygdaloid lesions on reversal learning in the deermouse.

Abstract Electrolytic lesions were placed in the basolateral, cortical or medial amygdaloid nuclear groups in male deeermice using the stereotaxic atlas for this species. Sham-operated and intact control groups were also included in the study. After allowing the animals a two-week recuperative period, they were tested in a black sheet metal T-shaped water maze especially constructed for mice. Following habituation to the water maze, all animals were run through original learning and four reversal learning stages. Results indicate that a decrement of learning occurred in animals with lesions in the cortical or basolateral amygdaloid nuclear groups while those animals with lesions in the medial amygdaloid area did not exhibit any significant changes when compared to either the sham-operated or intact control groups.

Relationship of wheel-running activity to post-wheel running plasma testosterone and corticosterone levels: A behavior-genetic analysis☆

Abstract Recombinant inbred (RI) strains of mice, their progenitor strains, and reciprocal F 1 hybrids were compared with regard to wheel-running activity. The resulting strain distribution pattern (SDP), backcross data, and testing with congenic lines suggested a genetic model with a major locus for wheel-running. Correlations of the SDP for wheel-running and SDPs for testosterone and corticosterone levels determined immediately after testing were low and nonsignificant. Thus, all 3 phenotypic traits measured exhibited genetic variation, but variation in wheel-running was unrelated to variation in corticosterone and testosterone levels following a wheel-running experience.

MAZE LEARNING: A GENETIC INVESTIGATION IN THE MOUSE

Recombinant inbred strains, their progenitor strains, and their reciprocal F1 hybrids were tested for maze learning in the Lashley III maze and in the Y-water maze. The resulting pattern of strain distribution suggested that the genetic model provided by the RI strains is based on at least two, and possibly many more, loci. There was no evidence of maternal effects or heterosis. Although the BALB/cBy strain represented an extremely high scoring strain for the Lashley maze and a low scoring strain for the Y-maze, presence of albino recombinant inbred strains intermediate to extreme strains and nonsignificantly different from pigmented recombinant inbred strains suggested that the albino gene was not responsible for the observed performance differences.