Role of dopaminergic and GABAergic mechanisms in discrete brain areas in phencyclidine-induced locomotor stimulation and turning behavior.
This study was designed to test whether phencyclidine (PCP)-induced turning behavior and locomotor stimulation result from the action of this drug on functionally different neuronal systems and different sites of the brain. PCP produced turning behavior towards the drug injection side with unilateral injection of PCP (50-100 micrograms) into the globus pallidus, but not the nucleus accumbens and the caudate nucleus. This turning behavior was strongly attenuated by a gamma-aminobutyric acid (GABA) antagonist, bicuculline, and by pimozide which reduces dopaminergic transmission in non-injection sites. Turning behavior induced by intraperitoneal injection of PCP (7.5 mg/kg) was enhanced by a GABA agonist, baclofen, and attenuated by GABA antagonists (bicuculline, picrotoxin). On the other hand, PCP produced significant locomotor stimulation, sniffing, rearing and forward locomotion with unilateral injection of 25-100 micrograms into the nucleus accumbens and the caudate nucleus. These behaviors were strongly antagonized by intraperitoneal injection of pimozide. The locomotor stimulation induced by intraperitoneal injection of PCP (5 mg/kg) was markedly enhanced by a small dose of methamphetamine and, by contrast, attenuated by reserpine, 6-hydroxydopamine, haloperidol, pimozide and a low dose of apomorphine which inhibits the release of dopamine by the stimulation of presynaptic receptors. These results suggest that PCP-induced turning behavior may be produced through stimulation of GABAergic transmission in the globus pallidus, although PCP-induced locomotor stimulation, sniffing, rearing and forward locomotion may be produced by increasing dopaminergic transmission in the nucleus accumbens and the caudate nucleus.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D002421:Caudate Nucleus / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005917:Globus Pallidus / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000502:physiology; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology; D012110:Reserpine / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*
D011954:Receptors, Dopamine; D011963:Receptors, GABA-A; D008694:Methamphetamine; D012110:Reserpine; D010622:Phencyclidine; D006220:Haloperidol; D004298:Dopamine