Phencyclidine induces D-1 dopamine receptor mediated Fos-like immunoreactivity in discretely localised populations of striatopallidal and striatoentopeduncular neurons in the rat

Phencyclidine (PCP), a non-competitive antagonist of the NMDA subtype of gl utamate receptor, which also acts as an indirect dopamine agonist and at si gma sites, can induce a long lasting psychotic state when taken acutely. It is well established that PCP is toxic to specific limbic structures and we have recently demonstrated that it induces apoptosis of a subpopulation of striatal neurons. These neurons lie predominantly in the dorsomedial stria tum and project to the globus pallidus. The mechanisms mediating this neuro nal death are unclear though manipulations of dopamine transmission can ind uce striatal c-Sos expression and continuous c-Sos expression has been impl icated in the molecular cascades controlling apoptosis. We accordingly unde rtook a series of experiments to determine the action of PCP on striatal Fo s-like immunoreactivity (FLI). PCP (80 mg/kg, s.c.) elicited FLI in three d istinct striatal areas, namely dorsomedial, dorsolateral and the nucleus ac cumbens. The level of PCP-induced FLI was consistently attenuated by the co -administration of the D-l antagonist, SCH 23390. Vehicle injections also i nduced modest levels of FLI in the dorsomedial striatum and the nucleus acc umbens which again were attenuated by SCH 23390. The type of striatal neuro n in which PCP-induced FLI was determined by the use of a retrograde anatom ical tracer. A colloidal gold tracer was thus injected into the major areas of termination of striatal projection neurons prior to the administration of PCP. This procedure demonstrated that the majority of the FLI positive s triatal cells were striatopallidal neurons, though some FLI positive striat oentopeduncular neurons were also seen. The potential pharmacological mecha nisms underlying the results are discussed. It is argued that the complex p attern of PCP-induced striatal FLI might be accounted for by a differential action upon extracellular dopamine levels whereby they are elevated in som e striatal areas and simultaneously reduced in others. (C) 1999 Elsevier Sc ience B.V. All rights reserved.