Similar dopamine-releasing effects of phencyclidine and nonamphetamine stimulants in striatal slices

Phencyclidine (PCP) elicits some behavioral and biochemical effects in rodents which resemble the effects of other central nervous system stimulants. Because an indirect dopaminergic agonist role has been proposed for PCP, we have compared the dopamine (DA)-releasing properties of PCP, amphetamine and certain nonamphetamine stimulants (methylphenidate, nomifensine, amfonelic acid). Striatal slices from male albino Sprague-Dawley rats were incubated with [³H]DA (10 nM) and then superfused in microperfusion chambers with a modified Tyrode's buffer (pH 7.4). Drug effects on [³H]DA release during depolarizing (40 mM KCl) and nondepolarizing (basal) conditions were determined by comparison with drug-free DA release rates in each preparation. PCP (3-100 μM) and all central nervous system stimulants tested produced a concentration-dependent increase of basal [³H]DA release (potency order: amfonelic acid, amphetamine > nomifensine, methylphenidate > PCP). At higher concentrations, PCP and the nonamphetamine stimulants also enhanced stimulated [³H]DA release. The effect of PCP on basal release was unchanged by the removal of extracellular calcium, addition of tetrodotoxin (1 μM) or pretreatment of rats with reserpine. Nomifensine (1 μM) enhanced the DA releasing actions of PCP and other nonamphetamine stimulants, but antagonized the DA releasing action of amphetamine. PCP, at concentrations which did not affect basal DA release (less than 1 μM), also antagonized the action of amphetamine. From these results, it appears that PCP enhanced DA release in a manner similar to the nonamphetamine class of central nervous system stimulants.