Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-06-19T20:08:34.042Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  11 September 2015

Hila M Ene
Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel Department of Psychology, Tel-Aviv University, Tel-Aviv, Israel
Nirit Z Kara
Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, Israel
Noa Barak
Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel
Tal Reshef Ben-Mordechai
Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel
Haim Einat*
Psychobiology Laboratory, School of Behavioral Sciences, Tel Aviv-Yaffo Academic College, Tel-Aviv, Israel Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beersheba, Israel College of Pharmacy, University of Minnesota, Duluth, MN, USA
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:



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.

Original Articles
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


1. Hershenberg, R, Gros, DF, Brawman-Mintzer, O. Role of atypical antipsychotics in the treatment of generalized anxiety disorder. CNS Drugs 2014;28:519533.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
6. McIntyre, RS, Wong, R. Asenapine: a synthesis of efficacy data in bipolar mania and schizophrenia. Clin Schizophr Relat Psychoses 2012;5:217220.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
10. Marston, HM, Young, JW, Martin, FD et al. Asenapine effects in animal models of psychosis and cognitive function. Psychopharmacology (Berl) 2009;206:699714.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
15. Kara, NZ, Einat, H. Rodent models for mania: practical approaches. Cell Tissue Res 2013;354:191201.Google Scholar
16. Haller, J, Alicki, M. Current animal models of anxiety, anxiety disorders, and anxiolytic drugs. Curr Opin Psychiatry 2012;25:5964.Google Scholar
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.Google Scholar
18. Deacon, RM. Hyponeophagia: a measure of anxiety in the mouse. J Vis Exp 2011; May 17;(51). pii: 2613. doi: 10.3791/2613.Google Scholar
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.Google Scholar
20. Borsini, F, Podhorna, J, Marazziti, D. Do animal models of anxiety predict anxiolytic-like effects of antidepressants? Psychopharmacology (Berl) 2002;163:121141.Google Scholar
21. Flaisher-Grinberg, S, Einat, H. Strain specific battery of tests for separate behavioral domains of mania. Front Psychiatry 2010;1:110.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
27. Crabbe, JC, Wahlsten, D, Dudek, BC. Genetics of mouse behavior: interactions with laboratory environment. Science 1999;284:16701672.Google Scholar
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.Google Scholar
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.Google Scholar
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.Google Scholar
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.CrossRefGoogle ScholarPubMed
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.Google Scholar