USE OF AMFONELIC ACID TO DISCRIMINATE BETWEEN CLASSICAL AND ATYPICAL NEUROLEPTICS AND NEUROTENSIN : AN IN VIVO VOLTAMMETRIC STUDY

Abstract Previous ex vivo studies have shown that the non-amphetamine stimulant amfonelic acid potentiates the increase in DOPAC induced by classical but not by atypical neuroleptics. In the present study, we have demonstrated that this neurochemical model can be used to discriminate typical from atypical neuroleptics in vivo usinf differential pulse voltammetry with carbon fibre electrodes. The study also compared the effect of intracerebroventricular (i.c.v.) administration of neurotensin, on extracellular striatal DOPAC following amfonelic acid, with the effects of both classical and atypical neuroleptics. Saline or amfonelic acid (2.5 mg/kg s.c.) were administered; followed 5 min later by the classical neuroleptics haloperidol, perphenazine, or the atypical neuroleptics clozapine, thioridazine, or by neurotensin. After drug administration extracellular striatal DOPAC was recorded every 5 min for 90 min. Amfonelic acid did not alter basal striatal DOPAC but potentiated the increase in DOPAC induced by haloperidol (1.0 and 0.05 mg/kg s.c.) and perphenazine (10 mg/kg s.c.). Both clozapine (30 mg/kg i.p.) and thioridazine (20 mg/kg s.c.) increased extracellular DOPAC, but pretreatment with amfonelic acid prevented the increase in DOPAC produced by both drugs. Neurotensin (10 μg, i.c.v.), in a similar manner to the atypical neuroleptics, increased extracellular DOPAC in the striatum and the effect was prevented by amfonelic acid. The present study demonstrates that pretreatment with amfonelic acid is a valuable tool to discriminate between classical and atypical neuroleptics in vivo. The results also indicate that neurotensin in the presence of amfonelic acid has a profile similar to the atypical neuroleptics.