Increases in h-3 -alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (ampa) receptor binding and mrna expression of ampa-sensitive glutamate receptor a (glur-a) subunits in rats withdrawn from butorphanol
An autoradiographic study of [(3)H]-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid(AMPA) receptor binding and an assessment of in situ hybridization of AMPA-sensitive glutamate receptor A (GluR-A) subunits in the rat brain were performed 7 h after withdrawal from butorphanol infusion. Animals were rendered dependent by intracerebroventricular (icv) infusion of butorphanol (26 nmol/microl/h) via osmotic minipumps for 3 d. Brain sections for binding of [(3)H]AMPA were incubated with 15 nM [(3)H]AMPA. The probes for in situ hybridization were labeled at its 3 cent end using terminal deoxynucleotidyl transferase and [(35)S]dATP. The highest degree of [(3)H]AMPA binding was shown in the hippocampus. The extent of [(3)H]AMPA binding was increased significantly in each of the brain areas examined, cortex, septum, caudate putamen, and hippocampus of rats, following withdrawal from butorphanol. The highest level of mRNA for GluR-A receptor for flop and flip subunits, was found in the dentate gyrus and in the CA3 region of the hippocampus. The amounts of mRNA for the flop form of GluR-A receptor were significantly increased in the cortex, caudate putamen, thalamus, and dentate gyrus of hippocampus of rat brain. The amounts of mRNA for the flip form of GluR-A receptor were markedly elevated in the cortex, thalamus, caudate putamen, and hippocampus. These findings suggest that increases in expression of mRNA for the GluR-A receptor and in the binding of AMPA to its receptor may play an important role during withdrawal from butorphanol dependence.