Effect of age on behavioral responses and tissue levels of apomorphine in the rat.

Rats of several ages between 2 and 24 months were tested for stereotyped behavioral responses to R(-)apomorphine-HCl (APO), a potent and selective dopamine agonist. Between 2 and 24 months, the ED50 for apomorphine decreased 2.5-fold (0.14-0.06 mg/kg, i.p.), as assessed by a microcomputer-assisted technique. Not only were older rats more sensitive to apomorphine, but the duration of the behavioral effects increased with age and showed a greater change at doses which were greater than the ED50. When levels of apomorphine in brain were assayed by liquid chromatography and electrochemical detection, there was a progressive increase in peak levels of the agent in the tissue as well as a delay in its elimination from brain, with increasing age. Moreover, there was a highly significant correlation between increased behavioral effect and the level of apomorphine in brain with increasing age (r greater than 0.8). These results indicate that increased levels in brain or decreased elimination of apomorphine may be an important factor contributing to a marked increase in behavioral sensitivity to apomorphine with age in the rat.