Effects of harmane, norharmane and harmine on apomorphine-induced pecking behavior in chick

Background and b-carboline alkaloids, also known as harmala's alkaloids have a wide spectrum of pharmacological actions including a stimulatory action on release of dopamine and other catecholamines in several brain regions and an inhibitory action on monoamine oxidase (MAO). These findings suggest that b-carbolines should alleviate at least some of the dopaminergic stereotyped behaviors. The purpose of present study is to determine the effects of b-carbolines harmane, norharmane and harmine on apomorphine-induced pecking behavior in chick. All experiments were carried out on male/female chicks (40-60 g). The modulatory effects of b-Carbolines on stereotyped behavior were assessed using the pecking behavior induced by apomorphine. Subcutaneous (s.c.) injection of apomorphaine (0.025 mg/kg, mixed agonist of dopamine D1/D2 receptors) induced pecking. The pecking response was counted by direct observation and recorded for a 40-minute period. S.C. injection of harmane (2.5-10 mg/kg) and harmine (1.25-5 mg/kg) significantly decreased the pecking behavior induced by apomorphine (0.25 mg/kg). The norharmane (2.5-15 mg/kg, i.p.) response was biphasic. The inhibitory effects of harmane, norharmane and harmine were blocked by flumazenil (5 mg/kg, i.e., 30 minutes before the test) or reserpine (5 mg/kg, i.e., 18 hours before the test). Results suggest that the modulatory effect of harmane, norharmane and harmine on the pecking behavior may be mediated through an inverse agonistic/monoaminergic mechanism.