Cerebral cortical 5-HT1 and 5-HT2 receptors of morphine tolerant-dependent rats

Abstract

The effect of chronic administration of morphine to rats on 5-HT1 and 5-HT2 receptors in the cerebral cortex was determined. Male Sprague-Dawley rats were implanted subcutaneously with 6 pellets of morphine (each containing 75 mg of morphine free base) during a 7 day period. Animals which served as controls were implanted with placebo pellets. The procedure for implantation of pellets produced a high degree of tolerance to and physical dependence on morphine in the rat. The tolerance to the analgesic and hyperthermic effects of morphine was demonstrated by decreased responses in the rats implanted with morphine pellet in comparison to the placebo-treated controls. The physical dependence was shown by the greater weight loss after removal of the pellet in the rats implanted with morphine pellets when compared to rats implanted with placebo pellets. The pellets were removed (withdrawn) and, after 6-8 h, the rats were sacrificed and the cerebral cortex was isolated. In another experiment the pellets were left in place (tolerant-dependent rats). The 5-HT1 and 5-HT2 receptors were characterized by using [3H]5-HT and [3H]spiroperidol as the ligands and unlabelled 5-HT and ketanserin, respectively, to determine non-specific binding. The [3H]5-HT bound to 5-HT1 receptors on membranes from the cerebral cortex of rats implanted with placebo pellets, at a single high affinity site, with a Bmax of 102 +/- 10 fmol/mg protein and a Kd of 6.02 +/- 0.98 nM. Implantation of morphine pellets, followed by removal of the pellets resulted in a 50% increase in the Bmax value of [3H]5-HT but the Kd values did not change.(ABSTRACT TRUNCATED AT 250 WORDS)