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The local cerebral metabolic effects of morphine in rats exposed to escapable footshock
B Gescuk1, S Lang, L J Porrino
1Laboratory of Behavioral Pharmacology, Boston University School of Medicine, MA 02118-2394.
Abstract:
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.
Insights
Morphine sulfate (MS) reduces glucose metabolism in specific brain regions, particularly limbic areas, during pain responses in rats. Footshock, however, generally increases overall brain activity.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Morphine sulfate (MS) is known to affect the emotional aspects of pain.
- Understanding the neural mechanisms of analgesia is crucial for pain management.
Purpose of the Study:
- To investigate the effects of morphine sulfate on local cerebral metabolic rates for glucose (LCMRglu).
- To identify specific brain structures modulated by morphine during a pain-inducing footshock paradigm.
Main Methods:
- Utilized the 2-deoxy-D-[1-14C]glucose (2-DG) method to measure LCMRglu in male F-344 rats.
- Administered morphine sulfate or saline prior to a footshock escape task.
- Compared brain glucose metabolism across four groups: control-saline, control-MS, footshock-saline, and footshock-MS.
Main Results:
- Morphine sulfate significantly decreased LCMRglu in limbic structures (e.g., diagonal band of Broca, lateral septum, medial amygdala) and midline thalamic nuclei (paraventricular, paratenial) in footshocked rats.
- Footshock exposure generally increased cerebral metabolism across 52 of 73 measured brain structures compared to saline controls.
- Specific structural effects of footshock were limited despite a generalized stimulatory impact.
Conclusions:
- Limbic and midline thalamic structures are key areas involved in morphine-induced analgesia.
- Footshock elicits a broad stimulatory effect on cerebral glucose metabolism.
- Morphine's analgesic effects are associated with reduced metabolic activity in specific emotional and pain-processing brain circuits.