NONCONTINGENT SHOCK DISRUPTS LEARNING IN SPINAL RATS: REVERSIBILITY BY INTRATHECAL OPIOID ANTAGONISTS DURING TESTING. R. L. Joynes & J. W. Grau. Department of Psychology, Texas A&M University, College Station, TX 77843.

Prior work suggests that spinal neurons can support a simple form of instrumental learning. In a typical experiment, spinal rats are given shock to one hind leg whenever that leg is extended (contingent group). Yoked subjects experience the same amount of shock irrespective of leg position (noncontingent group). Rats in the contingent, but not in the noncontingent, group learn to maintain a flexion response. In a subsequent test phase, all subjects receive contingent shock. Rats in the contingent group show facilitated learning (positive transfer). Even more interesting, subjects that previously experienced noncontingent shock fail to learn (a learning deficit).

We have shown that naltrexone, an opioid antagonist, injected i.p. blocks the induction of the learning deficit. In Experiment 1, we administered various doses of naltrexone intrathecally to verify that it was having its action on spinal neurons, and at the same time, extablished the effective intrathecal dose. Spinal rats received either 0, 3.5, 7, or 14 µg/µl of naltrexone intrathecally and then were given 6 min of noncontingent shock (training) or an equivalent period of restraint. After training, all subjects received 30 min of contingent shock (testing). We found that the learning deficit was eliminated in a dose dependent fashion, with 7 and 14 µg/µl being the most effective. In Experiment 2, we determined whether the opioid antagonist had its effect during training or testing. Spinal rats received either naltrexone (7µg/µl) or saline (9%) and then were given 6 min of noncontingent shock or an equivalent period of restraint. The next day, half of the subjects in each drug condition received naltrexone while the remaining subjects were given saline. Naltrexone only eliminated the learning deficit when it was administered prior to testing. Experiment 3 examined the impact of the selective mu, delta and kappa opioid antagonists, CTOP, naltrindole and nor-BNI. All drugs were administed at an equal molar concentration (18.5 nM). Spinal rats were given 6 min of either noncontingent shock or restraint. After this training period, subjects received an intrathecal injection of CTOP, naltrindole, nor-BNI or their vehicle. They were tested by applying 30 min of contingent shock. Nor-BNI eliminated the learning deficit while the other antagonists had no effect.

Symposium on Spinal Cord Plasticity, November 1998, Los Angeles CA.

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