Alpha-Fluoromethylhistidine Decreases the Leu-Enkephalinamide- and Morphine-Induced Corticosterone Response in Rats

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Abstract
The effect of inhibition of brain histamine synthesis by α-fluoromethylhistidine (α-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. α-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 induced by DADL or morphine injected into cerebral ventricles, and abolished the response to morphine given intraperitoneally. When α-FMH was administered intracerebroventricularly (50 μg), the maximum inhibition of the corticosterone response to DADL and morphine occurred 4 h after administration, which may suggest a weaker accessibility of α-FMH from the cerebral venticle 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 α-FMH considerably impairs the pituitary-adrenocortical response to the opioid δ- and μ-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.

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