Modification of the characteristics of dopamine transporter in brain regions and spinal cord of morphine tolerant and abstinent rats.

The specific binding of [3H]GBR 12935 to crude synaptosomal membranes of brain regions and spinal cord of morphine tolerant and abstinent rats was investigated. Male Sprague-Dawley rats were implanted with 6 morphine pellets each containing 75 mg of morphine base during a 7-day period. Placebo pellet implanted rats served as controls. Rats sacrificed without removal of the pellet were considered tolerant whereas those from which pellets were removed 16 hr prior to sacrificing were labeled abstinent. The binding of [3H]GBR 12935 was initially determined at a 1 nM concentration in all brain regions and spinal cord, which was followed by the determination of Bmax and Kd values in the corpus striatum, a highly enriched region for the dopamine transporter. In morphine tolerant rats, the binding of [3H]GBR 12935 was increased in the hypothalamus (182%) but was decreased in the corpus striatum (34%) and spinal cord (30%). The decrease in binding in the corpus striatum was due to an increase in the Kd value of [3H]GBR 12935. However, during morphine withdrawal, the binding of [3H]GBR 12935 was still higher in the hypothalamus (255%) but was decreased in the hippocampus (53%). Thus, chronic administration of morphine results in changes in the dopamine transporter function in selected brain regions and the spinal cord, and these changes are dependent upon whether or not the animals are undergoing the abstinence syndrome.