Changes in alpha2 adrenoreceptors in various areas of the rat brain after long-term administration of "mu" and "kappa" opiate agonists.

Clonidine, an alpha 2 adrenoreceptor agonist, is used to treat opiate dependent individuals who are experiencing the signs and symptoms of withdrawal. Changes in the apparent number of alpha 2 adrenoreceptors in specific areas of the rat brain have been observed after chronic morphine administration. In the present study, the effects of chronically administered morphine sulfate upon alpha 2 adrenoreceptors were compared to those of UM-1072, (+/-)-5,9-alpha-dimethyl-2-hydroxy-2-tetrahydro-furfuryl-6, 7-benzomorphan HCl, a "kappa" agonist which does not produce typical morphine-like dependence. The maximum number of specific binding sites (Bmax) and dissociation constants (KD's) for 3H-clonidine were measured with neural membranes isolated from saline or drug-treated rats. Rats were injected with saline, morphine or UM-1072, i.p., every 8 hr for 14 days. Doses of morphine ranged from 10 mg/kg, t.i.d., on the first three days to 100 mg/kg, t.i.d., on the last two days. Doses of UM-1072 covered a similar range. In control experiments, the Bmax's for specific binding of 3H-clonidine were (in fmoles/mg protein): hypothalamus, 142 +/- 7; amygdala, 141 +/- 3; brainstem, 70 +/- 2; parietal cortex, 130 +/- 4; hippocampus, 94 +/- 2; and caudate nucleus, 62 +/- 3. After chronic morphine treatment, the Bmax's were decreased significantly in all areas except the hippocampus. After chronic UM-1072 treatment, the Bmax's were decreased significantly in all areas studied. Neither treatment altered appreciably the KD's for 3H- clonidine. This study suggests that "mu" and "kappa" agonists might have similar actions upon noradrenergic systems in the brain.