INCREASED RELEASE OF EXCITATORY AMINO-ACIDS IN RAT LOCUS-COERULEUS INKAPPA-OPIOID AGONIST-DEPENDENT RATS PRECIPITATED BY NOR-BINALTORPHIMINE

Extracellular fluid levels of glutamate and aspartate in the locus coe ruleus (LC) during nor-binaltorphimine (nor-BNI)-precipitated withdraw al from butorphanol, (5 alpha,7 alpha,8 eta)-(+)-N-methyl-N-[7-(1-pyrr olidinyl)-1-oxaspiro [4,5] dec-8-yl]-benzeneacetamide (U-69,593), or m orphine were measured in rats. When the microdialysis probe was locate d in the core of the LC, increases in glutamate and aspartate were not ed after nor-BNI (48 nmol/50 mu l, LC)-precipitated withdrawal in rats that had been intracerebroventricularly infused with butorphanol (26 nmol/l mu l/h) or U-69,593 (26 nmol/10 mu l/h) for 3 days. The glutama te and aspartate levels in the LC markedly increased in the butorphano l- or U-69,593-dependent rats within 60 min following administration o f nor-BNI. However, there was no significant increase in levels of glu tamate, and only a slight increase in levels of aspartate, after nor-B NI treatment of the morphine (26 nmol/l mu l/h)-infused rats. Behavior al signs of withdrawal (teeth-chattering, wet-dog shakes, etc.) were o bserved following nor-BNI challenge in the butorphanol- or U-69,593-in fused rats, with only minimal signs in the morphine-infused rats, and none in the saline-infused controls. These results directly suggest th at kappa-opioid receptors and excitatory amino acids within the LC med iate withdrawal in animals dependent on butorphanol or U-69,593, but n ot on morphine. (C) 1997 Elsevier Science B.V.