Effects of harmane and other β-carbolines on apomorphine-induced licking behavior in rat

Abstract

Harmane, harmine and norharmane are β-carboline compounds which have been referred to as inverse agonists of benzodiazepine receptors. The effect of these compounds on apomorphine-induced licking behavior was studied in rats. Subcutaneous (s.c.) injection of apomorphine (0.5mg/kg) induced licking. The licking behavior was counted with a hand counter and recorded for a period of 75min by direct observation. Intraperitoneal (i.p.) injections of harmane (1.25–5mg/kg), harmine (2.5–10mg/kg) and norharmane (1.25–5mg/kg) significantly reduced the licking behavior. In rats pretreated with reserpine (5mg/kg, i.p., 18h before the test), the effects of harmane (4mg/kg, i.p.), harmine (7.8mg/kg, i.p.) and norharmane (2.5mg/kg, i.p.) were unchanged. When flumazenil (2mg/kg, i.p.) was administered 20min before apomorphine, it was able to antagonize the effects of harmane, harmine and norharmane. It was concluded that the β-carbolines harmane, harmine and norharmane reduce the licking behavior via an inverse agonistic mechanism located in the benzodiazepine receptors.