Blockade of morphine-induced increases in brain tryptophan hydroxylase activity by systemic pretreatment with CCK-8: no reversal by vagotomy.
The treatment of rats with CCK-8 suppresses the behavioral responses to subsequent injection of opiates. We have investigated the possibility that peripherally administered CCK-8 can also suppress a neurochemical response to opiates, namely the increase in brain tryptophan hydroxylase (TrpH) activity and tissue 5-hydroxyindole acetic acid (5-HIAA) which results from morphine administration. While morphine sulfate (4 mg/kg s.c.) roughly doubled brain TrpH activity and tissue 5-HIAA 40 min after injection, pretreatment with CCK-8 (5 micrograms/kg i.p., 10 min prior to morphine) completely abolished this neurochemical change induced by morphine. Doses of CCK-8 as low as 1 microgram/kg were effective in blunting the morphine-induced increase in cortical TrpH activity, but the desulfated form was ineffective at doses of 5 and 100 micrograms/kg. Subdiaphragmatic vagotomy did not prevent the effect of CCK-8.
Johannessen
J N
JN
Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, MD 20892.
Stuckey
J A
JA
Phan
T H
TH
Boadle-Biber
M C
MC
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology*; D014365:Tryptophan Hydroxylase / Q000378:metabolism*; D014630:Vagus Nerve / Q000502:physiology*
D009020:Morphine; D014365:Tryptophan Hydroxylase; D012844:Sincalide