Selective breeding of rats for high and low motor activity in a swim test: toward a new animal model of depression.

Because low motor activity ina swim test has been found to represent "depression-like" behavior in the rat, Sprague-Dawley (SD) albino rats were selectively bred for low motor activity (low struggling time/high floating time) in a swim test, while others were bred for high motor activity (high struggling time/low floating time). Eighty-four male and 42 female SD rats were initially purchased from Charles-River Breeding Laboratories in 1987, their behavior assessed in a 15-min swim test, and selective breeding carried out by mating those male and female rats that showed either low or high levels of motor activity in the test; results from behavioral testing of the first 18 generations produced by this selective breeding process are reported here. Two rat lines have been obtained, Swim Low-Active (SwLo) and Swim High-Active (SwHi) rats, which differ dramatically in swim-test behavior--SwLo rats show little struggling and much floating, while SwHi rats show the reverse. Activity scores of individual SwLo and SwHi rats now show no overlap. Selective breeding has produced bidirectional changes; that is, SwLo rats are considerably less active than randomly bred Sprague-Dawley albino rats, while SwHi rats are considerably more active than randomly bred rats. Measuring activity of SwLo and SwHi rats in other situations--ambulation in the home cage, open-field activity, exploratory activity in a novel, home cage-like situation, and immobility in the Porsolt swim test--revealed that differences are most pronounced when animals respond to acute challenges; under these conditions, SwHi rats show active, assertive behavior, whereas SwLo rats show a distinct absence of this type of response. When SwLo rats from the 8th to the 11th generations were given antidepressant medication [desipramine, (DMI), a tricyclic, or phenelzine, an MAO inhibitor], chronic but not acute administration of both drugs increased swim-test activity of SwLo rats. Buspirone, an anxiolytic, did not increase activity of SwLo rats. Use of animals selectively bred for high and low activity in the swim test may represent a new tool for studying physiological processes relevant to affective disorders and for testing antidepressant drugs/treatments.