The hypothalamus exhibits electrophysiologic evidence for morphine tolerance and dependence

The electrophysiologic effects of morphine (10 mg/kg) were studied in naive rats and after chronic morphine treatment for 5 days. Spontaneous multiunit activity was recorded from the ventromedial hypothalamus of unanesthetized, freely behaving rats implanted previously with permanent electrodes. In the naive condition, firing rates were altered by morphine in 60 of 73 multiunits. After development of tolerance, 28 of multiunits responded to the morphine challenge dose, in 22 of which the direction of change was opposite that observed in the naive condition. The other six were not affected by morphine on day 1 of the experiment and became sensitive to the morphine challenge dose only after the animal had become physically dependent on morphine. Predrug baseline activity in morphine physically dependent rats was altered in 23 recordings compared to the predrug activity obtained in morphine naive animals. Based on effects of morphine and naloxone, responses could be grouped into six electrophysiologic patterns which provide for separation of tolerance from the dependence phenomena.