Disposition of apomorphine in rat brain areas: relationship to stereotypy

Apomorphine-induced stereotyped behavior and apomorphine levels in plasma, striatum and nucleus accumbens were determined in rats at various intervals after a single i.p. injection of serial doses of apomorphine hydrochloride (0.625, 1.25, 2.5 and 5 mg/kg). Apomorphine disappeared from plasma in a mono-exponential mode with a half-life of about 10 min. In striatum and nucleus accumbens apomorphine concentrations peaked 10 min after administration, declining thereafter with a half-life comparable to that in plasma. Apomorphine was concentrated and distributed similarly in the two brain regions; the brain areas/plasma ratio was approximately seven for all doses tested. The rise of apomorphine levels in brain areas slightly preceded the behavioral response, whereas after the peak effect (20-30 min) the intensity of stereotypy declined almost parallel with the log drug concentrations. Plotting apomorphine levels in the tissues assayed against the drug response at the same interval for individual rats, regardless of dose, indicated a highly significant relation between the degree of behavioral effects and brain apomorphine levels. The threshold apomorphine concentrations for inducing stereotyped behaviour were 108 and 95 ng/g respectively in striatum and nucleus accumbens. These findings show that the time course and magnitude of the behavioral effects of apomorphine corresponded with its brain levels in 'dopaminergic' areas, suggesting that apomorphine-induced stereotyped behavior in rats can be described by a direct mechanism. Reserpine (5 mg/kg s.c.) enhanced the apomorphine stereotypy but did not affect apomorphine's disposition in brain and plasma.(ABSTRACT TRUNCATED AT 250 WORDS)