Binding characteristics of [3H]SCH 23390 in spinal cord and discrete brain regions of kappa-opiate tolerant-dependent and abstinent rats.

The effects of chronic administration of U-50,488H, a highly selective kappa-opiate receptor agonist, and its subsequent withdrawal were determined. The binding characteristics of [3H]SCH 23390 to dopamine D1 receptors were investigated on membranes of rat spinal cord and in discrete brain regions. Male Sprague-Dawley rats received U-50,488H (25 mg/kg) intraperitoneally twice a day for 4 days. Animals serving as controls received only vehicle. Two different treatment schedules were used. In one, rats were injected with U-40,588H on day 5 and were sacrificed 1 h later (tolerant-dependent rats). In another, the rats were sacrificed 16 h after the last injection of U-50,488H (abstinent rats). Chronic administration of U-50,488H resulted in the development of tolerance to its analgesic effect, as demonstrated by the decreased response to a challenge dose of U-50,488H compared to vehicle-injected rats. The binding characteristics (Bmax and Kd values) of [3H]SCH 23390 were unaffected in spinal cord and other regions of brain of tolerant-dependent rats. In U-50,488H-abstinent rats, Bmax values of [3H]SCH 23390 were increased in hypothalamic and striatal membranes, but Kd values were unaffected. These results suggest that, in U-50,488H-abstinent rats, dopamine D1 receptors are up-regulated in hypothalamus and striatum.