Down-regulation of hypothalamic 5-HT1A receptors in morphine-abstinent rats.

The effects of morphine tolerance-dependence and abstinence on 5-HT1A receptors in brain regions and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact (tolerant-dependent) and in the other they were removed (abstinent). Rats were killed, and spinal cords and brains were excised. Brain was dissected into seven regions (amygdala, hippocampus, hypothalamus, striatum, midbrain, pons + medulla and cortex). 5-HT1A receptors were characterized by using [3H]8-hydroxy-di-n-propylaminotetralin [( 3H]DPAT) as the ligand and unlabelled 5-HT to determine the non-specific binding. In morphine and placebo tolerant-dependent rats the binding of [3H]DPAT to 5-HT1A receptors in brain regions and spinal cord did not differ. The Bmax value of [3H]DPAT in the hypothalamus of morphine abstinent rats was decreased by 61.9%. No change in Bmax value was observed in other brain regions and spinal cord. The Kd values were unaffected. Subcutaneous administration of DPAT produced hypothermia in rats from which pellets had been removed. The intensity of DPAT-induced hypothermic response was greater in morphine abstinent rats as compared to placebo abstinent rats. Since DPAT is believed to have a major action on the presynaptic 5-HT neurons, it is concluded that in morphine abstinent rats 5-HT1A receptors are down-regulated in hypothalamus, but in morphine tolerant-dependent rats they are unaffected.