Enhanced binding of nor-binaltorphimine to ?-opioid receptors in rats dependent on butorphanol (original) (raw)

2003, Journal of Neuroscience Research

Autoradiographic characterization of binding for brain 1 ([ 3 H]CI-977) and 2 ([ 3 H]bremazocine) in the presence of DAMGO ([D-Ala 2 ,N-Me-Phe 4 ,Gly 5 -ol]-enkephalin), DP-DPE ([D-Pen 2 , D-Pen 5 ]-enkephalin), and U-69,593 opioid receptors, in the presence of different concentrations of a selective unlabeled -opioid receptor antagonist, norbinaltorphimine (nor-BNI), was performed in rats in which dependence on or withdrawal from butorphanol had been established. Dependence was induced by a 72 hr intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/l/hr; butorphanol dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 hr following termination (butorphanol withdrawal). IC 50 values from competition studies were estimated by fitting inhibition curves for both 1 -and 2opioid receptor assays. In both dependent and withdrawal groups, the IC 50 values obtained against [ 3 H]CI-977 or [ 3 H]bremazocine with nor-BNI were decreased (ratios of ϳ0.03-0.21 and ϳ0.05-0.42 vs. control, respectively) in brain regions, including frontal cortex, nucleus accumbens, claustrum, dorsal endopiriform nucleus, caudate putamen, parietal cortex, posterior basolateral amygdaloid nucleus, dorsomedial hypothalamus, hippocampus, posterior paraventricular thalamic nucleus, periaqueductal gray, substantia nigra, superficial gray layer of the superior colliculus, ventral tegmental area, and locus coeruleus, compared with control. These results indicate that, in butorphanol-dependent and butorphanol-withdrawal rats, the brain 1 -and 2 -opioid receptors developed a supersensitivity to antagonist binding.