Unilateral cerebral drug administration: pharmacokinetics of haloperidol and amphetamine

Following cannulation of the right common carotid artery of female Sprague-Dawley rats, 3 microCi (10 micrograms) of either [3H]haloperidol or [3H]amphetamine were infused. At various time intervals, drug concentrations were determined in the right and left striata, anterior forebrains, posterior forebrains and cerebella. One minute following unilateral intracarotid infusion of haloperidol, approximately a 90-100-fold right/left (ipsilateral/contralateral) difference in drug concentrations was attained in the striatum and the posterior forebrain, while more than a 75-fold difference was evident in the anterior forebrain. One minute following amphetamine infusion, a difference greater than 40-fold was seen in all forebrain structures. The right-left differences steadily declined with time as a result of the declining drug concentrations of the infused hemisphere. The pharmacokinetic parameters of both the distribution and elimination phases were similar in each forebrain region for both haloperidol and amphetamine. The kinetic parameters did, however, show specific drug differences. Bilateral drug concentrations in the striatum following intraperitoneal administration of amphetamine to unilaterally cannulated rats were nearly identical. Therefore, the cannulation procedure did not significantly alter the blood supply to either hemisphere. This is the first study to quantify drug concentrations and to analyze pharmacokinetic parameters following unilateral cerebral drug administration in conscious animals. This technique should be useful in studying functional and biochemical interhemispheric relationships as well as lateralized behaviors.