An Investigation of the Behavioral Mechanisms of Antipsychotic Action Using a Drug-Drug Conditioning Paradigm

We recently took a preclinical approach and investi-gated this issue using a well-established preclinical an-imal model of antipsychotics-conditioned avoidance re-sponse (CAR) model (Li et al., 2007, 2009; Mead and Li, in press). All currently available antipsychotics, at clin-ically relevant doses, selectively disrupt avoidance re-sponding to a conditional stimulus (CS, e.g. white noise) without altering escape responding to an unconditional stimulus (US, e.g. footshock) (Arnt, 1982; Wadenberg et al., 2001; Natesan et al., 2006). Thus, an antiavoidance re-sponding effect is frequently used as a validated behav-ioral index of ‘antipsychotic ’ property. Using this model, we found that rats treated with haloperidol (HAL), ris-peridone (RIS) and olanzapine (OLZ) daily for 7 consec-utive days showed a progressive across-session declin