Distribution of effects of the kappa-opioid agonist CI-977 on cerebral glucose utilization in rat brain.

The effects of the kappa-opioid agonist CI-977 upon local cerebral glucose utilization have been examined in conscious, lightly restrained rats to gain insight into the potential adverse effects of this neuroprotective agent. Cerebral glucose utilization was assessed quantitatively in 45 anatomically discrete brain regions by means of [14C]2-deoxyglucose autoradiography. The i.v. administration of CI-977 (0.03-3 mg/kg) induced relatively homogeneous patterns of altered cerebral glucose utilization with moderate statistically significant reductions (approximately 25%) being observed in 29 brain regions, and a statistically significant increase (approximately 40%) in one brain region, the lateral habenular nucleus. Glucose use throughout the entire neocortex and inferior colliculus was particularly sensitive to reduction (approximately 35%) following CI-977 administration, although there was only a limited dose dependency to the response. Minimal alterations in glucose use were observed in 15 of the 45 brain regions, particularly in the lower brain stem (e.g. superior olives, cochlear nucleus and median raphe) and forebrain limbic regions (e.g. septal nucleus, nucleus accumbens and mediodorsal thalamus). These data demonstrate that CI-977 produces widespread, anatomically organized alterations in function-related glucose use which contrast those seen previously with the NMDA receptor antagonists, thereby suggesting that CI-977 may be intrinsically safer as an in vivo neuroprotective agent.