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. 2004 Mar 10;24(10):2412–2420. doi: 10.1523/JNEUROSCI.5544-03.2004

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Copyright © 2004 Society for Neuroscience 0270-6474/04/242412-09.00/0

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Figure 6. — _Corticosterone with morphine on a delayed-escape paradigm of the Morris water maze. a, Delayed-escape was significantly enhanced by previous exposure to morphine, corticosterone, or corticosterone with morphine, indicated by the longer mean latencies to escape (black symbols; n = 5; p < 0.05 Mor_Mor/R compared with Mor_Mor/N; n = 6; p < 0.01 Cor_Mor/R compared with Cor_Mor/N; n = 6; p < 0.01 C-M_Mor/R compared with C-M_Mor/N; n = 6; p < 0.05 on days 9-10 C-M_C-M/R compared with C-M_C-M/N; F_(9,45) = 16.1, F_(9,45) = 28.6, F_(9,45) = 13.0, F_(9,45) = 11.0 for days 7-10, respectively), but not by previous saline exposure (n = 5; p > 0.05 Sal_Mor/R compared with Sal_Mor/N; p < 0.05 compared with other reinforced groups; F_(9,45) = 16.1, F_(9,45) = 28.6, F_(9,45) = 13.0, F_(9,45) = 11.0 for days 7-10, respectively). On the other hand, spatial learning was impaired in the group randomly rewarded with corticosterone with morphine after previous exposure to corticosterone with morphine (n = 6; p < 0.05 C-M_C-M/N compared with Sal_Mor/N; F_(9,45) = 16.1, F_(9,45) = 28.6, F_(9,45) = 13.0 for days 7-9, respectively) and in the group randomly rewarded with morphine after previous exposure to corticosterone (n = 6; p < 0.05 Cor_Mor/N compared with Sal_Mor/N; F_(9,45) = 28.6, F_(9,45) = 13.0, F_(9,45) = 11.0 for days 8-10, respectively). However, other nonreinforced groups performed the spatial learning task very well (white symbols; p > 0.05 cross groups compared with Sal_Mor/N). b, The reinforced groups, previously exposed to corticosterone or saline and later rewarded with morphine, and previously exposed to corticosterone with morphine and later rewarded with corticosterone with morphine, did not show morphine-seeking behavior after withdrawal for 5 d (Cor_Mor/R, Sal_Mor/R and C-M_C-M/R). However, the reinforced group, Mor_Mor/R, showed morphine-seeking behavior, as indicated by longer latencies to escape without reward, after withdrawal for 5 d but not 10 and 19 d, and a priming injection failed to reinstate on day 29 (n = 5; F_(9,45) = 9.8 on day 15, p < 0.05; F_(9,45) = 5.2 on day 20, F_(9,45) = 14.2 on day 29; p > 0.05 compared with Mor_Mor/N; p < 0.05 compared with C-M_Mor/R). Remarkably, persistent morphine-seeking behavior was found in the reinforced group, C-M_Mor/R, over the post-training period (n = 6; p < 0.05 C-M_Mor/R compared with other groups; F_(9,45) = 9.8, F_(9,45) = 5.2, F_(9,45) = 14.2 for days 15, 20, and 29, respectively). c, Net delay was calculated by subtracting the latencies of the nonreinforced group from that of its counterpart, the reinforced group, and then expressed as the mean of the net latencies over training days 7-10. Net delay was clearly enhanced by previous exposure to corticosterone with morphine, corticosterone, and morphine but not by previous exposure to saline (0.6 ± 2.2 sec for Sal_Mor; 17.4 ± 2.7 sec for Cor_Mor; 23.4 ± 5.9 sec for Mor_Mor; 41.0 ± 2.2 sec for C-M_Mor; 6.9 ± 2.1 sec for C-M_C-M). ^*p < 0.05 compared with Sal_Mor. Insets, Animals escape directly to the hidden platform in nonreinforced groups, e.g., C-M_Mor/N; animals swim slowly somewhere away from the hidden platform for a while and then rapidly escape to the hidden platform in the reinforced group, C-M_Mor/R, during the extinction test.