Research report Attenuation of context-specific inhibition on reversal learning of a stimulus /response task in rats with neurotoxic hippocampal damage Robert J. McDonald *, Caroline H. Ko, Nancy S. Hong Department of Psychology, University of Toronto, 100 St. George Street, Toronto, Ont., Canada M5S-3G3 Received 1 November 2001; received in revised form 2 April 2002; accepted 9 April 2002 Abstract Rats with hippocampal or sham lesions were trained on a stimulus  /response task developed for the 8-arm radial maze. After reaching a stringent learning criterion, different context manipulations were performed. In Experiment I, the different groups were transferred to an identical radial maze in a different room to determine the context specificity of the discrimination learning. Experiment I revealed that although rats with hippocampal lesions did not show a normal context detection effect, the expression of the discrimination was not context dependent for either the lesion or sham groups. In Experiment II, animals were trained to criterion on the discrimination task and then both groups were divided into sub-groups based on whether they would experience reversal training in the same or different context from original training. Experiment II indicated that animals with hippocampal lesions and shams reversed in a different context were significantly enhanced in reaching the learning criterion compared to either counterparts that were reversed in the same context. Reversal learning in rats with hippocampal lesions was faster than sham animals in the same context suggesting that the context-specific inhibition effect was hippocampal-based. After learning the reversal task, the groups of animals trained and reversed in different contexts were brought back into the original training context to test for competitive effects. Animals with hippocampal lesions that were reversed in the different context, did not show a competition between the most recently acquired discrimination and a context-specific association acquired during original training whereas sham animals in the same condition did. Taken together these results suggest that rats with hippocampal lesions do not acquire normal context-specific inhibition during discrimination learning. # 2002 Elsevier Science B.V. All rights reserved. Keywords: Learning; Stimulus  /response; Habit; Radial maze; Context; Context detection; Reversal learning; Inhibition; Latent inhibition; Competition; Hippocampus 1. Introduction There is evidence suggesting that the rat hippocampus is involved in place [45,47,41]; context [20,57]; and relational learning and memory [53,7]. Although debate persists on the precise conditions under which the rat hippocampus is critical for these paradigms, one theory suggests that rats with hippocampal damage have difficulty in acquiring these tasks when simple associa- tive solutions are not available to them during training [44,58,35]. This view suggests that rats with hippocam- pal damage are impaired on these different categories of learning and memory paradigms (place, context, rela- tional learning) because the computational requirements are similar. This critical computation may be the formation of a representation that encompasses various elements that define a specific event and the context in which it occurred [58]. In the intact animal, the hippocampus always appears to be encoding relation- ships among all elements of an experience into a representation of the event [33,16,43]. Early theorists have posited a general role for the hippocampus in a neural process similar to that of inhibition [10,29,17] in which associative processes lead to inhibition of behaviour because a conditioned stimulus (CS) becomes associated with non-reinforce- ment. This rather limited view of hippocampal function was initially abandoned and replaced by spatial, con- textual, and relational theories of the hippocampus * Corresponding author. Tel.:  /1-416-978-6489; fax:  /1-416-978- 4811 E-mail address: mcdonald@psych.utoronto.ca (R.J. McDonald). Behavioural Brain Research 136 (2002) 113 /126 www.elsevier.com/locate/bbr 0166-4328/02/$ - see front matter # 2002 Elsevier Science B.V. All rights reserved. PII:S0166-4328(02)00104-3