Spinalized rats that receive shock when 1 hind limb is extended (contingent shock) exhibit an increase in flexion duration, a simple form of instrumental learning. Rats that receive shock independent of leg position (noncontingent shock) do not exhibit an increase in flexion duration and fail to learn when tested with contingent shock 24 hr later. It appears that noncontingent shock induces an intraspinal modification that inhibits the capacity to learn. The authors propose that the mechanisms that underlie this effect depend on de novo protein synthesis. To evaluate this hypothesis, the authors gave spinalized rats the protein synthesis inhibitor Cycloheximide (CXM) or saline intrathecally prior to, or immediately after, noncontingent shock exposure. Twenty-four hours later, rats were tested with contingent shock. Rats that received the vehicle and noncontingent shock failed to learn. CXM-treated shocked rats learned normally, suggesting that the learning deficit depends on protein synthesis within the spinal cord.
Rationale-Spinal cord plasticity can be assessed in spinal rats using an instrumental learning paradigm in which subjects learn an instrumental response, hindlimb flexion, to minimize shock exposure. Prior exposure to uncontrollable intermittent stimulation blocks learning in spinal rats but has no effect if given before spinal transection, suggesting that supraspinal systems modulate nociceptive input to the spinal cord, rendering it less susceptible to the detrimental consequences of uncontrollable stimulation.Objective-The present study examines whether disrupting brain function with pentobarbital blocks descending inhibitory systems that normally modulate nociceptive input, making the spinal cord more sensitive to the adverse effect of uncontrollable intermittent stimulation.
Materials and methods-MaleSprague-Dawley rats received uncontrollable intermittent stimulation during pentobarbital anesthesia after (experiment 1) or before (experiment 2) spinal cord transection. They were then tested for instrumental learning at a later time point. Experiment 3 examined whether these manipulations affected nociceptive (thermal) thresholds.Results-Experiment 1 showed that pentobarbital had no effect on the induction of the learning deficit after spinal cord transection. Experiment 2 showed that intact rats anesthetized during uncontrollable intermittent stimulation failed to learn when later transected and tested for instrumental learning. Experiment 3 found that uncontrollable intermittent stimulation induced an antinociception in intact subjects that was blocked by pentobarbital.
Conclusions-The results suggest a surgical dose of pentobarbital (50 mg/kg) suppresses supraspinal (experiment 2) but not spinal (experiment 1) systems that modulate nociceptive input to the spinal cord by blocking the antinociception that is induced by this input (experiment 3).
These results indicate that the affective state produced by moderate shock has a negative valence that is sufficient to support a conditioned place aversion. This state is associated with a general sensitization that enhances processing of appetitive US.
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