Involvement of corticotropin-releasing factor receptor subtype 1 in morphine withdrawal regulation of the brain noradrenergic system.
Effects of pretreatment with the selective corticotropin-releasing factor (CRF) subtype 1 (CRF(1)) receptor antagonist, 2-(N-(2-methylthio-4-isopropylphenyl)-N-ethyl-amino-4-(4-(3-fluorophenyl)-1,2,3,6-tetrahydropyridin-1-yl)-6-methylpyrimidine (CRA1000) on the behavioral and biochemical changes after naloxone-precipitated morphine withdrawal were examined in ICR mice. Mice were chronically treated with morphine (8-45 mg/kg) for 5 days. Naloxone (3 mg/kg, s.c.) precipitated jumping, diarrhea, and body weight loss in morphine-dependent mice. In addition, 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and noradrenaline turnover (MHPG/noradrenaline) levels in the cerebral cortex were increased following naloxone challenge in morphine-dependent mice. However, 5-hydroxytriptamine turnover did not alter the increase following naloxone challenge in morphine-dependent mice. Pretreatment with CRA1000 (20 mg/kg, i.p.) attenuated the incidence of withdrawal signs and naloxone-precipitated increases in noradrenaline turnover. These results suggest that the activation of CRF(1) receptor may play an important role in the elevation of noradrenaline transmission, but not in 5-hydroxytriptamine transmission, in the cerebral cortex, which projects from the locus coeruleus during morphine withdrawal.
Funada
M
M
Section of Addictive Drugs Research, Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry, 1-7-3 Kohnodai, Chiba 272-0827, Ichikawa, Japan. mfunada@ncnp-k.go.jp
Hara
C
C
Wada
K
K
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003967:Diarrhea / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013997:Time Factors; D000099052:CRF Receptor, Type 1
D009292:Narcotic Antagonists; D011725:Pyridines; D011743:Pyrimidines; D018019:Receptors, Corticotropin-Releasing Hormone; D009270:Naloxone; C117406:CRA1000; D000099052:CRF Receptor, Type 1; D009020:Morphine; D009638:Norepinephrine