Separation of taste-aversion-prone and taste-aversion-resistant rats through selective breeding: Implications for individual differences in conditionability and aversion-therapy alcoholism treatment.

Abstract

Both rats and alcoholic humans display considerable variability in acquisition of illness-induced consummatory aversions. Differential conditionability may be a significant modulator of outcome in alcoholics who elect taste aversion (TA) approaches to abstinence facilitation. This is a report of the ongoing development of rat strains suitable for studies of biological bases of individual differences in TA conditionability. Sprague-Dawley-derived rats have been selectively bred over seven generations as strong or weak learners of a cyclophosphamide-induced saccharin aversion. Efficiency of aversion acquisition is a selectable propensity, as indicated by progressively divergent strain separation that attained significance in the second selected generation. Subjects have also been studied with respect to shock-motivated environmental avoidance (SMEA), but efficiency of SMEA performance has not been a selection factor. Results have produced an unexpected trend across generations indicative of a within-strain reversal of TA and SMEA learning efficiency. Continuation of this reversal in subsequent generations could have important implications for studies of genetic contributions to different learning capacities and for the selection of biologically appropriate noxious stimuli for aversive therapy treatments of various target problems.

Radial-maze learning by lines of taste-aversion-prone and taste-aversion-resistant rats

“…Selection was initiated at each of the two extremes of T A conditionability in randomly bred stock. At approximately 90 days of age, nonsibling matings were effected between the best learners and between the poorest learners of a cyclophosphamide-induced CT A to a normally preferred saccharin solution.An overview of the CT A methodology, which is detailed elsewhere (Elkins, 1986), is as follows: Fluiddeprived rats ingest a normally palatable saccharin solution and then are injected with cyclophosphamide. Cy- clophosphamide produces nausea in humans (Bernstein, 1978) and, presumably, elicits some comparable experience within rats, as indicated by its effectiveness as a T A conditioning agent.…”

“…A daily preference score is computed that indicates the percentage to which ingestion of the saccharin solution contributes to total daily fluid intake . A subject's mean saccharin preference score, averaged over an interval of at least 3 days, has been the behavioral index of breeder selection.Line differences in T A conditionability appeared within the 2nd selected (S-2) generation (Elkins, 1986). Ongoing selection across 22 additional generations has produced TA-prone (TAP) and TA-resistant (TAR) rats that now display marked between-line separation and low within-line variabilities in CT A acquisition.…”

“…An overview of the CT A methodology, which is detailed elsewhere (Elkins, 1986), is as follows: Fluiddeprived rats ingest a normally palatable saccharin solution and then are injected with cyclophosphamide. Cy- clophosphamide produces nausea in humans (Bernstein, 1978) and, presumably, elicits some comparable experience within rats, as indicated by its effectiveness as a T A conditioning agent.…”

“…In an attempt to clarify possible genetic contributions to individual differences in T A learning propensities, Elkins (1986) undertook a program of CT A-based bidirectional selective breeding of SpragueDawley-derived rats. Selection was initiated at each of the two extremes of T A conditionability in randomly bred stock.…”

“…Line differences in T A conditionability appeared within the 2nd selected (S-2) generation (Elkins, 1986). Ongoing selection across 22 additional generations has produced TA-prone (TAP) and TA-resistant (TAR) rats that now display marked between-line separation and low within-line variabilities in CT A acquisition.…”