CHRONIC ESCAPABLE FOOTSHOCK CAUSES A REDUCED RESPONSE TO MORPHINE IN RATS AS ASSESSED BY LOCAL CEREBRAL METABOLIC RATES

The 2-deoxy-D-[C-14]glucose (2-DG) method was used to examine the effe cts of morphine sulfate (MS) on local cerebral metabolic rates for glu cose (LCMR(glu)) in male F-344 rats required to turn a wheel manipulan dum in order to escape from nociceptive footshock. This nociceptive st imulus was identical with that utilized in a previous 2-DG study from this laboratory [15] except that animals were exposed to 15 daily 30 m in sessions of footshock prior to the 2-DG testing day rather than a s ingle footshock exposure. This allows a direct comparison of the effec ts of morphine in chronic and acute pain. Unlike the acute footshock s tudy, morphine in chronic footshock rats did not have a significant ef fect compared with chronic footshock alone in any of the 73 measured b rain structures, including limbic and midline thalamic structures prev iously shown to be important in morphine-induced analgesia during acut e pain [15]. Whereas 93% of measured cerebral structures showed decrea ses in LCMR(glu) following morphine administration in the acute footsh ock rats, morphine given to chronic footshock rats caused decreases in only 56% of the structures as compared with chronic footshock plus sa line. It is hypothesized that these differential effects of morphine a re due in part to a habituation to the chronic stressor such that chro nic footshock rats are less stressed than acute footshock rats. Additi onally, it is suggested that chronic exposure to pain produces a const ant elevation of opioid peptides leading to opioid receptor downregula tion and consequently morphine tolerance. These results demonstrate th at, even in the presence of the same nociceptive stimulus, morphine ca n have widely disparate effects on brain metabolism if there are diffe rences in the pain history of the animal.