Participation of Histamine in the Step-Through Active Avoidance Response and Its Inhibition by H₁-Blockers

Abstract

The effects of intravenous and intracerebroventricular administrations of certain H₁-blockers on the active avoidance response in rats were studied. Among the classic H₁-blockers used in this study: pyrilamine, diphenhydramine, promethazine and chlorpheniramine, promethazine was the most effective and chlorpheniramine the least in inhibiting the active avoidance response; namely, a variation of prolongation in the response latency of the avoidance response. Meanwhile, ketotifen most potently inhibited the active avoidance response when the drugs were administered intracere-broventricularly. Mequitazine, astemizole and oxatomide were weak depressants when administered by either route. Azelastine was less effective than the classic H₁-blockers by intravenous injection, while by intracerebroventricular injection, the inhibition was almost identical to those induced by the classic H₁-blockers. Intracerebroventricular injection of histamine was antagonized the prolonged latency in the avoidance response induced by pyrilamine or diphenhydramine. A similar effect was also produced by 2-methylhistamine, but 4-methylhistamine had no effect. Intracerebroventricular injection of acetylcholine was restored the retarded avoidance response induced by pyrilamine, but a dose 20 times greater than that of histamine was required. From these findings, it can be concluded that inhibition of the active avoidance response induced by H₁-blockers may be exerted through interaction with H₁-receptors in the brain.