Effects of harmane and other β-carbolines on apomorphine-induced licking behavior in rat.
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 (0.5 mgkg) induced licking. The licking behavior was counted with a hand counter and recorded for a period of 75 min by direct observation. Intraperitoneal (i.p.) injections of harmane (1.25-5 mgkg), harmine (2.5-10 mgkg) and norharmane (1.25-5 mgkg) significantly reduced the licking behavior. In rats pretreated with reserpine (5 mgkg, i.p., 18 h before the test), the effects of harmane (4 mgkg, i.p.), harmine (7.8 mgkg, i.p.) and norharmane (2.5 mgkg, i.p.) were unchanged. When flumazenil (2 mgkg, i.p.) was administered 20 min 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.