Arachidonyl ethanolamide (anandamide) activates the parvocellular part of hypothalamic paraventricular nucleus

Arachidonyl ethanolamide, anandamide (ANA) was administered to male rats via a single i.p. injection at a dose of 0.02 mg/kg. In an parallel experiment ANA injection was preceded by the injection of SR 141716 (1.0 mg/kg), a selective and potent cannabinoid receptor antagonist. We observed using FOS protein immunocytochemistry that the parvocellular part of hypothalamic paraventricular nucleus (PVN) was activated as soon as 45 min. after ANA injection, i.e. the PVN showed an increased FOS immunoreactivity (FOSir). The peak level of FOSir was observed 90 min, after treatment. Meanwhile serum ACTH and corticosterone levels, as measured by radioimmunoassay, also significantly increased. 180 min. following drug injection both FOSir and serum hormone levels and returned to normal. SR 141716 did not antagonize these effects of ANA. We postulate that the locus of action of ANA the activation of the hypothalamo-pituitary-adrenal (HPA) axis is the parvocellular part of PVN. This activation may occur via a possible central cannabinoid receptor for which SR 141716 is not an effective antagonist. The rapid central response and activation of the HPA axis further support the view that ANA may be a central neurotransmitter or neuromodulator.