The conditioned avoidance response test re-evaluated: is it a sensitive test for the detection of potentially atypical antipsychotics?

The present review discusses the history and paradigm of the conditioned av oidance response (CAR) in rats for the detection of potential antipsychotic activity of drugs. In addition, the role of dopamine (DA) D-2, serotonin ( 5-HT)(2A/2C) alpha(1), 5-HT, DA D-4 muscarinic and glutamate receptors in t he suppression of CAR induced by various classes of drugs is evaluated. Fin ally, data investigating brain sites of action for the mediation of CAR beh avior is discussed. It is concluded that the CAR test, originally found to be sensitive for the detection of antipsychotic drugs with high affinity as antagonists for bra in dopamine receptors, is also sensitive for the detection of potentially a ntipsychotic compounds acting primarily via neurotransmitter receptors othe r than the DA D-2 receptor. Furthermore, the review confirms the importance of the nucleus accumbens(shell) in the mediation of effects on CAR produce d by traditional, as well as atypical antipsychotic drugs. (C) 1999 Elsevie r Science Ltd. All rights reserved.