Morphine is well known to produce tolerance and dependence. The mechanisms for these phenomena are not clearly understood and there are a number of conflicting reports that chronic
morphine administration decreases, increases, or leaves unchanged the number of
opioid binding sites. We examined the potency of MScontin (oral
controlled-release preparation of
morphine) to induce
morphine dependence and also determined the change of mu, delta and
kappa opioid receptor types in brain homogenates obtained from
morphine-dependent guinea-pigs. 1. Guinea-pigs were implanted subcutaneously with MScontin (300 mg.kg-1) and
naloxone was employed to precipitate jumping behavior of
withdrawal symptoms at various times. The highest degree of physical dependence was observed on the 2nd day after implantation. Therefore, this period was chosen to investigate
opioid receptor binding assay. 2. Two days after implantation, the binding of 3H-DAGO (mu agonist), 3H-DPDPE (delta agonist) and 3H-U69593 (kappa agonist) to brain membranes prepared from
morphine dependent and control guinea-pigs was determined. Scatchard plot of the saturation binding data revealed an increase in Bmax values (maximum specific binding) and no change in the Kd values (equilibrium dissociation constants) of 3H-opioid
ligand bindings obtained from
morphine-dependent animals as compared to controls. These results indicate that brain mu, delta and
kappa opioid receptors are up-regulated in
morphine dependent guinea-pigs.