Morphine deteriorates spatial memory in sodium salicylate treated rats

Tolerance and cross-tolerance for the effects of morphine (M) and sodium salicylate on nociception and learning were examined. The anti-nociceptive effects were measured by using the classic tail flick (TF) and hot plate (HP) tests and learning was measured with the Morris water maze (MWM). Tolerance or cross-tolerance was induced by daily injection (i.p.) of morphine sulfate (10 mg/kg for 7 days) or sodium salicylate (300 mg/kg for 6 days). The injection of sodium salicylate increased both TF and HP latencies. This anti-nociceptive effect was progressively decreased across six injections and tolerance to sodium salicylate was developed. When M was injected to sodium salicylate-tolerant rats, a weakened anti-nociceptive effect was seen, indicating cross-tolerance to M. Acute treatment with M also increased TF latency. This anti-nociceptive effect was successively decreased across seven injections and tolerance to M was developed. When sodium salicylate was injected to M-tolerant rats, a diminished anti-nociceptive effect was seen, indicating cross-tolerance to sodium salicylate. Acute M impaired water maze performance, while chronic M and sodium salicylate had no effects on MWM performance. However, when M was injected to rats that had received sodium salicylate after each training trial for 7 days, these rats spent less time in target quadrant as compared to M and saline groups. It is concluded that chronic sodium salicylate induces tolerance to anti-nociceptive effects of M and vice versa. Also chronic salicylate may produce lasting metaplastic changes in brain mechanisms behind spatial learning and memory, which can be visualized in cross-sensitization to morphine.