enkephalinamide-leu--ala(2)- and alpha-fluoromethylhistidine

The effect of inhibition of brain histamine synthesis by alpha-fluoromethylhistidine (alpha-FMH) on the pituitary adrenocortical activity stimulated by D-Ala-D-Leu-enkephalinamide (DADL) and morphine was investigated indirectly through corticosterone secretion in conscious rats. alpha-FMH (20 mg/kg i.p.) drastically reduced the whole brain histamine content, measured 2 h later. The same pretreatment also considerably reduced the corticosterone response to morphine given intraperitoneally. When alpha-FMH was administered intracerebroventricularly (50 micrograms), the maximum inhibition of the corticosterone response to DADL and morphine occurred 4 h after administration, which may suggest a weaker accessibility of alpha-FMH from the cerebral ventricle to the brain structures involved in pituitary-adrenocortical stimulation. The corticosterone responses were not related to the core temperature changes. These results indicate that inhibition of brain histamine synthesis by alpha-FMH considerably impairs the pituitary-adrenocortical response to the opioid delta- and mu-receptor agonists DADL and morphine. They also suggest that neuronal histamine is significantly involved in the central stimulation of the pituitary-adrenal axis by opioids.

Topics: Animals; Body Temperature; Brain; Corticosterone; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Histamine Release; Histidine Decarboxylase; Male; Methylhistidines; Morphine; Pituitary-Adrenal System; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu