Differentiation of apomorphine from bromocriptine, piribidel and TRH by chronic administration in rats

The dopaminergics, apomorphine (1 mg/kg), bromocriptine (1, 10 and 20 mg/kg), piribidel (5, 20 and 40 mg/kg) and thyrotropin releasing hormone (TRH) (1, 10 and 20 mg/kg), were each injected SC in rats at 09.00 h and 18.00 h daily for at least 20 days. Only apomorphine induced a behavioral syndrome (AIBS) in both male and female rats, characterized by tail-vibration (within 5 days) and a hyperexcitement which included defecation, mounting (in males only), jumping, cliff-jumping, climbing and, after 9-11 days, sham-boxing. Chronically-treated rats were placed, individually, in a small glass cylinder; only those rats on apomorphine displayed an increase in excitement and constant circling, almost exclusively in a counterclockwise direction. Acute pretreatment with d-butaclamol (0.64 mg/kg, SC), but not with the l-enatiomer, blocked the AIBS. No sham-boxing occurred when d-amphetamine (1 and 5 mg/kg), bromocriptine (10 and 20 mg/kg), piribidel (1, 5, 10, 20 and 40 mg/kg) and TRH (1 and 20 mg/kg) were substituted for apomorphine; in the presence of noise, substitution of piribidel (5, 10, 20 and 40 mg/kg) elicited mild displays of sham-boxing. When apomorphine (1 mg/kg) was substituted for chronically-administered bromocriptine (20 mg/kg) bidirectional circling, but no AIBS, was seen. Apomorphine, when substituted for piribidel or TRH, did not induce circling or the AIBS. Tolerance did not develop to the AIBS over 90 days; 31 days after the final injection, the AIBS could again be elicited by a single dose of apomorphine (1 mg/kg). The behavioral syndrome linked with chronic administration of apomorphine, and the associated reverse tolerance, differentiate apomorphine from the other test compounds. Nevertheless, the partial cross-sensitization between apomorphine and piribidel, and between bromocriptine and apomorphine, provides evidence of common mechanisms at the functional level. The AIBS represents an additional model that may be used in the study of dopamine receptors in vivo.