[Study of behavioral pharmacology on rats. Tranquilizing effects induced by endogenous or exogenous bradykinin].

Abstract

Unlabelled: This study was investigated on the mechanism of the sedative state, tranquilization induced by bradykinin (BK) and kallikrein (KAL). The drugs used in this study were as follows: KAL as endogenous BK promoter; prostaglandins (PGs) as a material of analogous action of BK; indomethacin and mepacrine as the inhibitors of PG-synthesis; eugenol as the OH- scavenger and the PGE-synthesis potentiator; angiotensin converting enzyme inhibitor as BK potentiator B. All drugs were dissolved in Hartmann's solution (lactate Ringer's solution) and 10 microliters of solution was injected into the lateral ventricle of rats, according to the Myers' procedure. Then, the rat behavior was estimated, by means of monitoring spontaneous movement. A high performance liquid chromatography (HPLC) was used for detecting alteration of monoamines and prostaglandins in the rat brain on sedative state after BK or KAL injection.

Results: 1) A 2-phase alteration of spontaneous movement was occurred within 30 min after BK or KAL icv-injection with behavioral specificity as follows: two exciting states and one sedative state. 2) A great increase of spontaneous movement evoked by BK or KAL was accompanied by exciting state as follows: jumping, wet dog response, struggle and scratching response, rearing and exploration. 3) A great decrease of spontaneous movement evoked by BK or KAL was accompanied with sedative state as follows: crouching with piloerection and closed eyes, catalepsy, preening and moisturizing and grooming. 4) PGE1 icv-injection was also carried out to clarify the involvement in the BK- or KAL-induced behavioral alteration. Consequently caused PGE1 the similar result to BK or KAL. 5) ACEI elongated and enhanced the exciting state or sedative state evoked by BK or KAL. 6) It was clear that BK reduced levels of monoamines in the rat hypothalamus: levels of norepinephrine(NE), epinephrine(E), dopamine(DA) and 5-hydroxytryptamine (5-HT) were decreased to 72.5%, 53.5%, 71.2% and 75.0% of control, respectively. Reduction of catecholamines in the hypothalamus was produced by increase of PGs and subsequently occurred sedative state of rats. 7) BK- or KAL-induced exciting state was enhanced by PG- synthesis inhibitor, especially the cyclo-oxygenase inhibitor indomethacin, but the sedative state was weakened. On the contrary, eugenol, an OH- scavenger, elongated and intensified the sedative state. Detection with HPLC showed remarkable increase of levels of PGs in the rat brain during the sedative state: the level of PGE2 was 27.5% increase of control and the level of PGE2 alpha was also 54.8% increase of control, respectively.