Male hooded Wistar rats were treated chronically once daily with morphine sulfate (20 mg/kg SC) after completing a session in an operant chamber. Periodical challenges with morphine (8 mg/kg) prior to the operant session established that tolerance development was virtually complete within 10 days. The morphine-treated rats were more sensitive to the behavioral suppressing effects of apomorphine, a dopamine agonist, and pilocarpine, an acetylcholine agonist, when administered in the tolerant state (morphine given 30 min prior to operant session), regardless of whether they were administered peripherally or directly into the striatum. Conversely, the morphine-treated rats were less sensitive to both agonists when administered in the withdrawal state (morphine given 24 h prior to the operant session). In animals undergoing a similar regimen of chronic morphine treatment, receptor binding studies revealed a lowered affinity (Higher KD apparent) for the dopamine receptor in the striatum of morphine-withdrawn rats, using 3H-spiroperidol as the ligand. The morphine-withdrawn rats also appeared to have fewer muscarinic cholinergic receptors (lower Bmax), using 3H-QNB as the ligand. The also had a lower concentration of membrane-bound phosphodiesterase modulator protein. In general, no significant differences were observed for the above parameters in the morphine-tolerant rats. These behavioral and neurochemical studies are consistent with the view that morphine-tolerant rats are supersensitive to dopamine and acetylcholine agonists and morphine-withdrawn rats are subsensitive. © 1979 Springer-Verlag.
