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Chunk #30 — 4. Discussion

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Plasticity associated with escalated operant ethanol self-administration during acute withdrawal in ethanol-dependent rats requires intact matrix metalloproteinase systems.
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However, the possibility existed that FN-439 has rate decreasing effects that were independent of FN-439 MMP inhibition. To rule this out, those animals that received aCSF during the post-dependence self-administration sessions and had shown normal escalation were treated with an acute infusion of FN-439 prior to a final self-administration session. The results showed that FN-439 did not suppress responding and confirmed that once escalation had occurred, MMP inhibition had no impact on operant self-administration rates. Another question that arose from the results of the second experiment was the possibility that MMP inhibition could cause a permanent suppression of learning. To confirm that this was not the case, those animals that were originally treated with FN-439 that did not escalate were treated with aCSF under the same conditions. The results showed that over the course of three sessions, ethanol self-administration escalated and therefore, normal negative reinforcement learning was observed.