Examination of the cerebral metabolic effects of morphine in rats exposed to acute and chronic footshock and conditioned stress
Gescuk, Bryan D.
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The purpose of this research was to determine, using the 2[14C]deoxyglucose autoradiographic method, the local cerebral metabolic rates for glucose (LCMRglu) after the administration of morphine or saline in rats escaping from acute or chronic footshock or exposed to conditioned stress. All animals were given morphine (4mg/kg, sc) or saline 7 days, 3 days and 10 minutes prior to the tracer injection. The effects of stimulation in the acute and chronic footshock studies revealed that an identical noxious stimulus may not have similar effects on functional cerebral activity if there are differences in experience with the str1xsor. The results of the conditioned stress experiment demonstrate that simply placing an animal in an environment previously associated with footshock is sufficient to elicit changes in LCMRglu. The effects of morphine in the control and acute footshock experiments were similar in that nearly all of the 73 analyzed brain regions (99% and 93%, respectively) showed decreases in LCMRg1u. Morphine, however, caused fewer decreases (56%) in the chronic footshock study. Interestingly, the percentage of structures showing decreases in the conditioned stress study (79%) was approximately halfway between the effects seen in the two footshock studies. Morphine in the presence of acute footshock, compared to acute footshock alone, caused significant decreases in elements of the limbic telencephalon, basal forebrain and thalamic midline (paraventricular and paratenial nuclei). On the other hand, morphine did not cause any significant decreases in these structures (or others) in the chronic footshock study. Rather, the combination of morphine and chronic footshock, compared to morphine alone, caused significant increases in several brainstem structures previously implicated in opioid analgesia: the locus coeruleus, gigantocellular reticular nucleus and raphe magnus. Additionally, significant effects were seen in basal ganglia structures which are normally associated with the motor system. The effects seen in these structures, along with the significant effect demonstrated in the parafasicular thalamic nucleus, suggest that morphine works to attenuate pain in animals exposed to chronic footshock via neural networks responsible for sensorimotor reactions to pain. Alternatively, animals exposed to chronic footshock may have developed tolerance to the effects of morphine. The effects of morphine, however, in the chronic footshock experiment are much different from those seen in the acute footshock study where morphine acts primarily in limbic structures and midline thalamus to attenuate the affective reaction to pain.
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