Modification of brain and spinal cord dopamine D1 receptors labeled with [3H]SCH 23390 after morphine withdrawal from tolerant and physically dependent rats

Abstract

The effect of morphine tolerance-dependence and abstinence on dopamine D1 receptors in brain regions and spinal cord was determined in rats. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets, each containing 75 mg of morphine free base. Rats serving as controls were implanted with placebo pellets. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by decreased body weight and colonic temperature after morphine pellet removal (withdrawal). Two sets of animals were used for receptor binding studies. In one, the pellets were left intact and in the other, the pellets were removed. Eighteen hours after pellet removal, the rats were sacrificed. [3H]SCH 23390 [( R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1-3-benzapine- 7-ol]) bound to brain region and spinal cord membranes of placebo pellet-implanted rats at a single high affinity site. In rats treated chronically with morphine and then withdrawn, the binding of [3H]SCH 23390 to membranes of spinal cord, hypothalamus and striatum was increased but the binding to amygdalar membranes was decreased in comparison with placebo-treated rats. The changes in binding were due to the changes in Bmax values; the Kd values were unaffected. The behavioral responses to a selective dopamine D1 receptor agonist, SKF 38393 [( 1-phenyl-2,3,4,5-tetrahydro (1H)-3-benzapine-7,8-diol hydrochloride]), were also enhanced in morphine-withdrawn rats when compared to placebo controls.(ABSTRACT TRUNCATED AT 250 WORDS)