Neurophysiological assessment of site specific effects of chronic morphine administration in freely behaving rats.

Sensory evoked responses were recorded simultaneously from five structures (caudate nucleus, septum, periaqueductal gray, parafascicular nucleus and reticular formation) reported to play roles in morphine's acute actions (analgesia, dyskinesia) and in the development of tolerance. Daily recordings were made from unanesthetized male Holtzman rats before and after a challenge dose of 10 mg/kg of morphine sulfate over a four day period while tolerance was induced by multiple daily injections of morphine. Three patterns of changes were observed in the individual components of the evoked responses. 1) The challenge dose caused an initial increase in the amplitudes of the P2 and N2 components of the response in the naive rats. This effect was attenuated with each day of drug administration until day four, when the challenge dose was observed to exert no effect. This pattern occurred in the parafascicular nucleus and the septum. 2) Initial increase in P2 and N2 components by morphine was augmented for 2-3 days, after which there was a sharp drop to control values by day four. This pattern was observed in the caudate nucleus and the periaqueductal gray region. 3) Morphine caused a mixture of increases and null effects in the components over the four days. This effect was observed in the reticular formation.