The 2-deoxy-D-[1-C-14]glucose (2-DG) method was used to examine the ef
fects of morphine sulfate (MS) on local cerebral metabolic rates for g
lucose (LCMR(glu)) in male F-344 rats required to turn a wheel manipul
andum in order to escape from nociceptive footshock. Four groups of ra
ts were studied: control-saline, control-MS, footshock-saline and foot
shock-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 pa
in, MS administered to rats exposed to footshock caused a significant
decrease in LCMR(glu) compared to footshock-saline rats in limbic stru
ctures such as the diagonal band of Broca, lateral septum, bed nucleus
of the stria terminalis, horizontal limb of the diagonal band, habenu
lar complex and medial amygdala. Additionally, two components of the m
idline thalamus with extensive connections with the limbic system, the
paraventricular and paratenial thalamic nuclei, were similarly affect
ed by morphine. Footshock caused an overall increase in cerebral metab
olism as 52 of 73 measured structures demonstrated increases in activi
ty compared to saline control, however, statistically significant effe
cts in specific structures were limited. These results identify limbic
and midline thalamic structures important in morphine-induced analges
ia and indicate that footshock tends to have a generalized stimulatory
effect on LCMR(glu).