Skip to main content Accessibility help

Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice

  • Hila M Ene (a1) (a2), Nirit Z Kara (a1) (a3), Noa Barak (a1), Tal Reshef Ben-Mordechai (a1) and Haim Einat (a1) (a3) (a4)...



A number of atypical antipsychotic drugs were demonstrated to have anxiolytic effects in patients and in animal models. These effects were mostly suggested to be the consequence of the drugs’ affinity to the serotonin system and its receptors. Asenapine is a relatively new atypical antipsychotic that is prescribed for schizophrenia and for bipolar mania. Asenapine has a broad pharmacological profile with significant effects on serotonergic receptors, hence it is reasonable to expect that asenapine may have some anxiolytic effects. The present study was therefore designed to examine possible effects of asenapine on anxiety-like behaviour of mice.


Male ICR mice were repeatedly treated with 0.1 or 0.3 mg/kg injections of asenapine and then tested in a battery of behavioural tests related to anxiety including the open-field test, elevated plus-maze (EPM), defensive marble burying and hyponeophagia tests. In an adjunct experiment, we tested the effects of acute diazepam in the same test battery.


The results show that diazepam reduced anxiety-like behaviour in the EPM, the defensive marble burying test and the hyponeophagia test but not in the open field. Asenapine has anxiolytic-like effects in the EPM and the defensive marble burying tests but had no effects in the open-field or the hyponeophagia tests. Asenapine had no effects on locomotor activity.


The results suggest that asenapine may have anxiolytic-like properties and recommends that clinical trials examining such effects should be performed.


Corresponding author

Haim Einat, Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, 2 Rabenu Yeruham Street, Tel-Aviv 6818211, Israel. Tel: +972 3 6802536; Fax: +972 3 6802526; E-mail:


Hide All
1. Hershenberg, R, Gros, DF, Brawman-Mintzer, O. Role of atypical antipsychotics in the treatment of generalized anxiety disorder. CNS Drugs 2014;28:519533.
2. Barnett, SD, Kramer, ML, Casat, CD, Connor, KM, Davidson, JR. Efficacy of olanzapine in social anxiety disorder: a pilot study. J Psychopharmacol 2002;16:365368.
3. Bandelow, B, Chouinard, G, Bobes, J et al. Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. Int J Neuropsychopharmacol 2010;13:305320.
4. Peng, Z, Zhang, R, Wang, H et al. Ziprasidone ameliorates anxiety-like behaviors in a rat model of PTSD and up-regulates neurogenesis in the hippocampus and hippocampus-derived neural stem cells. Behav Brain Res 2013;244:18.
5. McLelland, AE, Martin-Iverson, MT, Beninger, RJ. The effect of quetiapine (Seroquel) on conditioned place preference and elevated plus maze tests in rats when administered alone and in combination with (+)-amphetamine. Psychopharmacology (Berl) 2014;231:43494359.
6. McIntyre, RS, Wong, R. Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia. Clin Schizophr Relat Psychoses 2012;5:217220.
7. Tarazi, FI, Neill, JC. The preclinical profile of asenapine: clinical relevance for the treatment of schizophrenia and bipolar mania. Expert Opin Drug Discov 2013;8:93103.
8. Tarazi, FI, Moran-Gates, T, Wong, EH, Henry, B, Shahid, M. Asenapine induces differential regional effects on serotonin receptor subtypes. J Psychopharmacol 2010;24:341348.
9. Tait, DS, Marston, HM, Shahid, M, Brown, VJ. Asenapine restores cognitive flexibility in rats with medial prefrontal cortex lesions. Psychopharmacology (Berl) 2009;202:295306.
10. Marston, HM, Young, JW, Martin, FD et al. Asenapine effects in animal models of psychosis and cognitive function. Psychopharmacology (Berl) 2009;206:699714.
11. McLean, SL, Neill, JC, Idris, NF, Marston, HM, Wong, EH, Shahid, M. Effects of asenapine, olanzapine, and risperidone on psychotomimetic-induced reversal-learning deficits in the rat. Behav Brain Res 2010;214:240247.
12. Snigdha, S, Idris, N, Grayson, B, Shahid, M, Neill, JC. Asenapine improves phencyclidine-induced object recognition deficits in the rat: evidence for engagement of a dopamine D1 receptor mechanism. Psychopharmacology (Berl) 2011;214:843853.
13. Marston, HM, Martin, FD, Papp, M, Gold, L, Wong, EH, Shahid, M. Attenuation of chronic mild stress-induced ‘anhedonia’ by asenapine is not associated with a ‘hedonic’ profile in intracranial self-stimulation. J Psychopharmacol 2011;25:13881398.
14. Ene, HM, Kara, NZ, Einat, H. The effects of the atypical antipsychotic asenapine in a strain-specific battery of tests for mania-like behaviors. Behav Pharmacol 2015;26:331337.
15. Kara, NZ, Einat, H. Rodent models for mania: practical approaches. Cell Tissue Res 2013;354:191201.
16. Haller, J, Alicki, M. Current animal models of anxiety, anxiety disorders, and anxiolytic drugs. Curr Opin Psychiatry 2012;25:5964.
17. Prut, L, Belzung, C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 2003;463:333.
18. Deacon, RM. Hyponeophagia: a measure of anxiety in the mouse. J Vis Exp 2011; May 17;(51). pii: 2613. doi: 10.3791/2613.
19. Broekkamp, CL, Rijk, HW, Joly-Gelouin, D, Lloyd, KL. Major tranquillizers can be distinguished from minor tranquillizers on the basis of effects on marble burying and swim-induced grooming in mice. Eur J Pharmacol 1986;126:223229.
20. Borsini, F, Podhorna, J, Marazziti, D. Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology (Berl) 2002;163:121141.
21. Flaisher-Grinberg, S, Einat, H. Strain specific battery of tests for separate behavioral domains of mania. Front Psychiatry 2010;1:110.
22. Fonken, LK, Finy, MS, Walton, JC et al. Influence of light at night on murine anxiety- and depressive-like responses. Behav Brain Res 2009;205:349354.
23. Decker, S, Grider, G, Cobb, M et al. Open field is more sensitive than automated activity monitor in documenting ouabain-induced hyperlocomotion in the development of an animal model for bipolar illness. Prog Neuropsychopharmacol Biol Psychiatry 2000;24:455462.
24. Bahi, A, Schwed, JS, Walter, M, Stark, H, Sadek, B. Anxiolytic and antidepressant-like activities of the novel and potent non-imidazole histamine H(3) receptor antagonist ST-1283. Drug Des Dev Ther 2014;8:627637.
25. Griebel, G, Belzung, C, Perrault, G, Sanger, DJ. Differences in anxiety-related behaviours and in sensitivity to diazepam in inbred and outbred strains of mice. Psychopharmacology (Berl) 2000;148:164170.
26. Gard, PR, Haigh, SJ, Cambursano, PT, Warrington, CA. Strain differences in the anxiolytic effects of losartan in the mouse. Pharmacol Biochem Behav 2001;69:3540.
27. Crabbe, JC, Wahlsten, D, Dudek, BC. Genetics of mouse behavior: interactions with laboratory environment. Science 1999;284:16701672.
28. Lapin, IP. Only controls: effect of handling, sham injection, and intraperitoneal injection of saline on behavior of mice in an elevated plus-maze. J Pharmacol Toxicol Methods 1995;34:7377.
29. Kane, JM, Mackle, M, Snow-Adami, L, Zhao, J, Szegedi, A, Panagides, J. A randomized placebo-controlled trial of asenapine for the prevention of relapse of schizophrenia after long-term treatment. J Clin Psychiatry 2011;72:349355.
30. Maina, G, Ripellino, C. The risk of metabolic disorders in patients treated with asenapine or olanzapine: a study conducted on real-world data in Italy and Spain. Expert Opin Drug Saf 2014;13:11491154.
31. Michalak, EE, Guiraud-Diawara, A, Sapin, C. Asenapine treatment and health-related quality of life in patients experiencing bipolar I disorder with mixed episodes: post-hoc analyses of pivotal trials. Curr Med Res Opin 2014;30:711718.
32. Caresano, C, Di Sciascio, G, Fagiolini, A et al. Cost-effectiveness of asenapine in the treatment of patients with bipolar I disorder with mixed episodes in an Italian context. Adv Ther 2014;31:873890.


Related content

Powered by UNSILO

Effects of repeated asenapine in a battery of tests for anxiety-like behaviours in mice

  • Hila M Ene (a1) (a2), Nirit Z Kara (a1) (a3), Noa Barak (a1), Tal Reshef Ben-Mordechai (a1) and Haim Einat (a1) (a3) (a4)...


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.