The local cerebral metabolic effects of morphine in rats exposed to escapable footshock.

The 2-deoxy-D-[1-14C]glucose (2-DG) method was used to examine the effects of morphine sulfate (MS) on local cerebral metabolic rates for glucose (LCMRglu) in male F-344 rats required to turn a wheel manipulandum in order to escape from nociceptive footshock. Four groups of rats were studied: control-saline, control-MS, footshock-saline and footshock-MS. All animals were administered MS (4 mg/kg, s.c.) or saline 7 days, 3 days and 10 min prior to the start of the 2-DG experiment. In agreement with its well-known effect on the emotional component of pain, MS administered to rats exposed to footshock caused a significant decrease in LCMRglu compared to footshock-saline rats in limbic structures such as the diagonal band of Broca, lateral septum, bed nucleus of the stria terminalis, horizontal limb of the diagonal band, habenular complex and medial amygdala. Additionally, two components of the midline thalamus with extensive connections with the limbic system, the paraventricular and paratenial thalamic nuclei, were similarly affected by morphine. Footshock caused an overall increase in cerebral metabolism as 52 of 73 measured structures demonstrated increases in activity compared to saline control; however, statistically significant effects in specific structures were limited. These results identify limbic and midline thalamic structures important in morphine-induced analgesia and indicate that footshock tends to have a generalized stimulatory effect on LCMRglu.