Differential effects of chronic morphine and naloxone on opiate receptors, monoamines, and morphine-induced behaviors in preweanling rats.

Rats were administered either chronic morphine, naloxone or saline from 1 to 21 days of age. At 22 days of age, animals were sacrificed and various CNS areas were assayed for specific binding of [3H]naloxone and steady-state levels of norepinephrine, dopamine and serotonin, as well as turnover of norepinephrine and dopamine. In addition, some animals at 22 days of age were assessed for morphine-induced changes in activity, hot-plate paw-lick latency, and rectal body temperature. Chronic naloxone treatment produced an increase in the number of ligand binding sites in hypothalamus, striatum and cortex, but did not alter monoamine systems or the efficacy of morphine. In contrast, chronic morphine treatment produced tolerance to the hypoactive and antinociceptive effects of morphine, but did not alter ligand binding or monoamine systems. These results demonstrate that developing opiate receptor systems in brain are more responsive to chronic receptor blockade than to chronic receptor activation and that an alteration in the development of opiate receptor systems does not necessarily produce a concomitant alteration in either monoamine systems or the behavioral efficacy of morphine.