Conditioned avoidance response test

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The conditioned avoidance response (CAR) test, also known as the active avoidance test, is an animal test used to identify drugs with antipsychotic-like effects.[1][2][3][4][5] It is most commonly employed as a two-way active avoidance test with rodents.[6][2][5] The test assesses the conditioned ability of an animal to avoid an unpleasant stimulus.[1][4][2][7] Drugs that selectively suppress conditioned avoidance responses without affecting escape behavior are considered to have antipsychotic-like activity.[1][4][2] Variations of the test, like testing for enhancement of avoidance and escape responses, have also been used to assess other drug effects, like pro-motivational and antidepressant-like effects.[8][9][10][11]

Dopamine D2 receptor antagonists, like most classical antipsychotics, are active in the CAR test once occupancy of the dopamine D2 receptor reaches around 70%.[1][2] Dopamine D2 receptor partial agonists like aripiprazole are likewise active in the test.[1][12] Serotonin 5-HT2A receptor antagonists can enhance suppression of conditioned avoidance responses in the test.[1][13] Various other types of drugs have also been found to be active in the CAR test.[1] The effects of drugs that are active in the test are thought to be mediated by inhibition of signaling in the nucleus accumbens or ventral striatum of the mesolimbic pathway.[2][1][14] This is a major brain area involved in behavioral activation and motivation.[15][16][17][18]

The CAR test was developed in the 1950s soon after the discovery of antipsychotics.[2][19] It is one of the oldest animal tests of antipsychotic-like activity.[4][2] Other animal tests that are used to evaluate antipsychotic-like activity include inhibition of drug-induced hyperactivity or stereotypy, reversal of drug-induced prepulse inhibition deficits, and restoration of latent inhibition.[4][12][7]

  1. ^ a b c d e f g h Wadenberg ML (January 2010). "Conditioned avoidance response in the development of new antipsychotics". Curr Pharm Des. 16 (3): 358–370. doi:10.2174/138161210790170085. PMID 20109144.
  2. ^ a b c d e f g h Wadenberg ML, Hicks PB (1999). "The conditioned avoidance response test re-evaluated: is it a sensitive test for the detection of potentially atypical antipsychotics?". Neurosci Biobehav Rev. 23 (6): 851–862. doi:10.1016/s0149-7634(99)00037-8. PMID 10541060.
  3. ^ Ayyar P, Ravinder JR (June 2023). "Animal models for the evaluation of antipsychotic agents". Fundam Clin Pharmacol. 37 (3): 447–460. doi:10.1111/fcp.12855. PMID 36410728.
  4. ^ a b c d e Gobira PH, Ropke J, Aguiar DC, Crippa JA, Moreira FA (2013). "Animal models for predicting the efficacy and side effects of antipsychotic drugs". Braz J Psychiatry. 35 Suppl 2: S132–S139. doi:10.1590/1516-4446-2013-1164. PMID 24271225.
  5. ^ a b Wadenberg, Marie-Louise G. (2011). "Schizophrenia Key Essays: Active Avoidance". In Fleischhacker, W. Wolfgang; Stolerman, Ian P. (eds.). Encyclopedia of Schizophrenia. Tarporley: Springer Healthcare Ltd. pp. 5–12. doi:10.1007/978-1-907673-96-2_1. ISBN 978-1-907673-17-7.
  6. ^ Cite error: The named reference RowleyBristowHutson2001 was invoked but never defined (see the help page).
  7. ^ a b Cite error: The named reference ForrestCotoSiegel2014 was invoked but never defined (see the help page).
  8. ^ Cite error: The named reference Knoll2003 was invoked but never defined (see the help page).
  9. ^ Cite error: The named reference Healy2000 was invoked but never defined (see the help page).
  10. ^ Cite error: The named reference ShirayamaChaki2006 was invoked but never defined (see the help page).
  11. ^ Cite error: The named reference ShirayamaIshidaIwata2004 was invoked but never defined (see the help page).
  12. ^ a b Ginovart, Nathalie; Kapur, Shitij (19 September 2009). "Dopamine Receptors and the Treatment of Schizophrenia". The Receptors. Totowa, NJ: Humana Press. pp. 431–477. doi:10.1007/978-1-60327-333-6_16. ISBN 978-1-60327-332-9. ISSN 1048-6909.
  13. ^ Svensson, Torgny H. (2003). "Preclinical effects of conventional and atypical antipsychotic drugs: defining the mechanisms of action". Clinical Neuroscience Research. 3 (1–2). Elsevier BV: 34–46. doi:10.1016/s1566-2772(03)00017-3. ISSN 1566-2772.
  14. ^ Cite error: The named reference TangYangShi2022 was invoked but never defined (see the help page).
  15. ^ Cite error: The named reference SalamonePardoYohn2016 was invoked but never defined (see the help page).
  16. ^ Cite error: The named reference SalamoneCorrea2024 was invoked but never defined (see the help page).
  17. ^ Cite error: The named reference SalamoneCorreaFerrigno2018 was invoked but never defined (see the help page).
  18. ^ Cite error: The named reference SalamoneCorrea2012 was invoked but never defined (see the help page).
  19. ^ Kapur S, Mamo D (October 2003). "Half a century of antipsychotics and still a central role for dopamine D2 receptors". Prog Neuropsychopharmacol Biol Psychiatry. 27 (7): 1081–1090. doi:10.1016/j.pnpbp.2003.09.004. PMID 14642968.