The effect of
phencyclidine and other drugs on
sodium-dependent high-affinity uptake of
choline in the rat hippocampus and/or striatum was investigated and related to the behavioral changes induced by these agents. In contrast to
atropine (40.0 mg/kg), which increased the uptake of
choline in synaptosomes from both the rat hippocampus and striatum, the administration of
phencyclidine (54.4 mg/kg), 30 min prior to sacrifice, caused a significant decrease in the uptake of
choline in synaptosomes from rat striatum (but not hippocampus). This effect of
phencyclidine could be seen up to 1 hr after administration of
drug, but by 3.5 hr the uptake of
choline was essentially back to normal. The inhibition of striatal uptake of
choline occurred at a time when brain levels of
phencyclidine and its metabolites were at their highest, and the animals were essentially immobile; it did not appear to correlate with behavioral changes (including stereotypy and
catalepsy) seen at later times after this dose of
phencyclidine (54.4 mg/kg), or at earlier times after smaller doses.
Amphetamine (6.0 mg/kg) also decreased the uptake of
choline in the striatum.
Haloperidol (2.0 and 3.0 mg/kg) blocked both the
phencyclidine and
amphetamine-induced inhibition of the uptake of
choline but only the behavioral effects of
amphetamine. The data suggest that
phencyclidine may be exerting an indirect effect on the uptake of
choline in the striatum via its interaction with the dopaminergic system. However, this neurochemical effect of
phencyclidine could not be related in any simple way to the immobility, stereotypy or
catalepsy caused by this
drug.