Cortical evoked potential changes during self-administration of morphine by rats

We investigated associative and physiologic changes during the development of dependence and subsequent withdrawal from morphine. Rats were trained to lever press for intravenous doses of morphine. Electrical stimulation of one foreleg (CS+) was paired with the administration of morphine after a lever press. Stimulation of the other foreleg (CS−) occurred explicitly unpaired with the morphine administration. Cortical evoked potentials from 11 subjects were analyzed. Changes in peak-to-peak amplitude for both CS+ and CS− elicited evoked potentials due to morphine administration were found in three components. In one component (latency of 98 to 197 ms), the change in amplitude during conditioning for the CS+ elicited evoked potentials was different from the CS− elicited evoked potentials. The difference in the change in amplitude in the CS+ and CS− evoked potential components was defined as a conditioned response. In two of the three animals that survived to the testing phase, the associative response appeared to persist after withdrawal.