Naloxone alters the local metabolic rate for glucose in discrete brain regions associated with opiate withdrawal.
The current 2-deoxy-D-[1-14C]glucose investigation was performed to test the hypothesis that endogenous opioids influence basal synaptic activity within discrete brain regions. To examine this hypothesis, the effects of naloxone (1.0 mg/kg s.c.) on local cerebral metabolic rate for glucose (LCMRglu) in 84 brain regions were compared to saline controls. The specificity of naloxone's effects for opioid receptors was assessed by the coadministration of the opiate agonist morphine in a separate group. In naloxone-treated rats, there was a significant decrease in LCMRglu in the locus coeruleus (LC) and an increase in the central nucleus of the amygdala (CAMY), supporting a tonic influence of endogenous opioids on these regions. These metabolic changes were reversed by coadministered morphine, indicating that naloxone's metabolic actions are specific for opioid receptors. Based on the role of the LC and CAMY in opiate withdrawal, the present results suggest a subthreshold naloxone precipitated withdrawal from endogenous opioids. Although morphine administered alone significantly reduced LCMRglu in 16 brain regions, these did not include the LC or the CAMY. These results identify brain regions in which synaptic activity is under tonic modulation by endogenous opioids.
Kraus
M A
MA
Department of Pharmacology, Boston University School of Medicine, MA 02118, USA.
Piper
J M
JM
Kornetsky
C
C
D000679:Amygdala / Q000187:drug effects; D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003847:Deoxyglucose; D004347:Drug Interactions; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006400:Hematocrit; D008125:Locus Coeruleus / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018847:Opioid Peptides / Q000009:adverse effects*; D051381:Rats; D011916:Rats, Inbred F344; D013312:Stress, Physiological / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism
D000701:Analgesics, Opioid; D001786:Blood Glucose; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D009270:Naloxone; D009020:Morphine; D003847:Deoxyglucose; D005947:Glucose