Brain sites involved in mu-opioid receptor-mediated actions: a 2-deoxyglucose study

Brain regions that may be functionally involved in the neuropharmacological actions of mu-opioid agonists have been examined in conscious rats using the quantitative [14C]2-deoxyglucose autoradiographic technique. At 0.5 microgram and 1 microgram intracerebroventricularly the highly selective mu-opioid receptor agonist D-Ala2, MePhe4, Gly-ol5-enkephalin effected statistically significant increases as well as statistically significant decreases in regional glucose utilization: in limbic structures, such as hippocampal formation, medial amygdala and lateral septum, glucose utilization was most prominently increased after D-Ala2, MePhe4, Gly-ol5-enkephalin; glucose utilization was further increased in the lateral habenular nucleus, the hypothalamus, ventromedial nucleus and dorsal raphe; whereas decreases were found in the mamillary body and anterior thalamus. Glucose utilization in structures associated with somatosensory and nociceptive processing was increased in the central gray of the midbrain and decreased in the nucleus gelatinosus. Only increases in glucose utilization were produced by D-Ala2; MePhe4, Gly-ol5-enkephalin in brain regions involved in motor control, including the globus pallidus, the substantia nigra, pars reticulata, the nucleus ruber and the cerebellum, and brain regions involved in visual processing--the visual cortex and superior colliculus deep layer. It is concluded that this pattern of regional changes underlies the mu-opioid receptor-mediated antinociceptive-, epileptogenic-, memory- and mood-modulating actions of mu-opioid agonists.