PharmacologyBiochemistry& Behavior, Vol. 33, pp. 649-654. PergamonPress plc, 1989. Printed in the U.S.A. 0091-3057/89 $3.00 + .00 A Pretest Procedure Reliably Predicts Performance in Two Animal Models of Inescapable Stress ROBERT C. DRUGAN, .1 PHIL SKOLNICK,t STEVEN M. PAUL* AND JACQUELINE N. CRAWLEY .2 *Clinical Neuroscience Branch, NIMH and "~Laboratory of Neuroscience, NIDDK, NIH, Bethesda, MD 20892 Received 9 November 1988 DRUGAN, R. C., P. SKOLNICK, S. M. PAUL AND J. N. CRAWLEY. A pretest procedure reliably predicts performance in two animal models of inescapable stress. PHARMACOL BIOCHEM BEHAV 33(3) 649-654, 1989.--Rats exposed to inescapable tailshock fail to learn a shuttle-escape task 24 hours later, an effect referred to as "learned helplessness." However, within most rat strains only 10-50% of the animals tested develop this syndrome. In the present study a significant correlation was found between rats that displayed learned helplessness on the first test and those that displayed learned helplessness on a second test performed either 2 weeks (r = .80, p<0.001) or 4 weeks (r = .74, p<0.001) later. An analysis of the mean session latency of the shuttlebox task in these two tests suggested a bimodal distribution of animals that failed and learned. A significant correlation was found between individual rats that learned this task on the first test and those which learned this task 2 or 4 weeks later. Similarly, in the "behavioral despair" test, a significant correlation was observed for floating time for individual rats on the first test and on the second test either 2 (r = .72, p<0.001) or 4 weeks (r = .63, p<0.001) later. However, for the forced-swim test, a unimodal and rather graded response was observed across individual subjects. Thus, performance on the first round predicted performance on the second round in both models. When rats experienced the learned helplessness paradigm on round 1 and the behavioral despair paradigm in round 2, there was no correlation between rats that displayed helplessness following inescapable tailshock and the rats that demonstrated "behavioral despair" on a later test. While both the "learned helplessness" and the "behavioral despair" models may assess the ability of individual animals to "cope" with stressors, the lack of cross-predictability strongly suggests that the two models may be mediated by different neurochemical mechanisms. Learned helplessness Foreed-swim test Stress Depression Anxiety INESCAPABLE shock has been reported to produce a variety of effects including failure to learn a simple escape task 24 hours later (17, 18, 25), subsequent inactivity in the presence of shock (2, 6, 7, 10), analgesia (12,13), reduced aggressiveness or subordinate behavior (15, 19, 22, 23), enhanced susceptibility to growth of implanted tumors (27,28), development of gastric ulcers (29) and immunosuppression (13). Some authors have suggested that "learned helplessness" paradigms employing inescapable shock represent animal models of depression (26,30). This view is supported by the pharmacologic profile of drugs that block this syndrome (26). The use of learned helplessness as an animal model for studying the neurochemistry of stress-induced psychopathology has been confounded by the problem that not all rats exposed to inescapable shock develop the syndrome. In fact, the percentage of rats developing learned helplessness varies considerably, de- pending upon the strain (32), the difficulty of the escape response (24), and the type of escape task employed (1,14). At present, there is no reliable method to distinguish animals that will develop these syndromes. Neurochemical analyses are often performed immediately or within several hours after inescapable shock. Using animals after the learning task (24 hours later) for biochem- ical analysis introduces yet another source of variance, since the animals that subsequently fail to learn the shuttlebox task have experienced greater footshock exposure than the animals which learned the task. The development of a behavioral pretest proce- dure that reliably identifies rats that will develop the learned helplessness syndrome while permitting sufficient time after the shuttlebox escape task for any changes in neurochemical param- eters to return to baseline, could allow assay of more homoge- neous groups. Forced-swimming-induced "behavioral despair" has been re- ported to be another animal model of behavioral depression IPresent address: Department of Psychology, Brown University, Providence, RI 02912. 2Requests for reprints should be addressed to Jacqueline N. Crawley, Ph.D., Unit on Behavioral Neuropharmacology, Clinical Neuroscience Branch, NIMH, Building 10, Room 4N214, 9000 Rockville Pike, Bethesda, MD 20892. 649