Morphine dependence and protracted abstinence: regional alterations in CNS radioligand binding

Rats (Fisher F-344) were given free access to a 10% sucrose solution containing 0.5 mg/ml morphine sulfate (controls received the sucrose vehicle only) as their sole source of fluid. Daily morphine intake averaged 119 +/- 21 mg/kg, an amount sufficient to induce physical dependence. After 18 days on this regimen, the control and dependent subjects were sacrificed. A protracted abstinence group was weaned from morphine by reducing its concentration in the vehicle by 20% over the next 5 days, followed by a 5-week drug-free period before sacrifice concurrent with the other groups. These subjects showed no signs of an abstinence syndrome. Binding assays for alpha-2 adrenergic sites (3H-clonidine), beta-1/beta-2 adrenergic sites (3H-dihydroalprenolol), and dopaminergic (D2)/serotonergic (5-HT2) sites (3H-spiroperidol) were performed on tissue from frontal cortex, hippocampus, striatum, and brainstem. No alterations in 3H-clonidine or 3H-dihydroalprenolol binding were observed in dependence or protracted abstinence, suggesting that noradrenergic systems are well-regulated both during dependence and in protracted abstinence. 3H-spiroperidol binding was significantly elevated in the striatum (D2 sites) and hippocampus (5-HT2 sites) during dependence. Hippocampal 3H-spiroperidol binding returned to control levels in protracted abstinence, reflecting a morphine-induced change in 5-HT2 binding sites which had normalized by 5 weeks post-drug. Striatal 3H-spiroperidol binding was significantly decreased below control levels after withdrawal, suggesting that alterations of D2 sites in this structure may play a role in protracted abstinence.