Behavioural pharmacology Anxiolytic-like effects of alverine citrate in experimental mouse models of anxiety Deepali Gupta n , Mahesh Radhakrishnan, Yeshwant Kurhe Department of Pharmacy, Birla Institute of Technology & Science, Pilani 333031, Rajasthan, India article info Article history: Received 15 July 2014 Received in revised form 28 August 2014 Accepted 28 August 2014 Available online 6 September 2014 Keywords: Alverine citrate Anxiolytic-like effects 5HT 1A antagonist Elevated-plus maze Hole-board Marble burying test abstract Anxiety disorders are widely spread psychiatric illnesses that are a cause of major concern. Despite a consistent increase in anxiolytics, the prevalence of anxiety is static; this necessitates the development of new compounds with potential activity and minimum unwanted effects. A serotonergic (5HT) system plays an important role in pathogenesis of anxiety and predominantly involves 5HT 1A receptor action in mediating anxiety-like behavior; the antagonism of 5HT 1A receptor has demonstrated to produce anxiolytic-like effects. Alverine citrate (AVC) is reported as a 5HT 1A antagonist; however, its effects on anxiety-like behavior are not investigated. Thus, the present study, by utilizing a neurobehavioral approach, examined the anxiolytic-like effects of AVC in experimental mouse models of anxiety. Mice were acutely treated with AVC (5–20 mg/kg, i.p.)/diazepam (DIA, 2 mg/kg, i.p.) and subjected to four validated anxiety models viz. elevated plus-maze (EPM), light/dark (L/D), hole-board (HB) and marble burying (MB) tests. AVC (15–20 mg/kg) and DIA significantly increased open arm activity in EPM, exploration in light chamber in L/D test, exploratory behavior in HB and reduced MB behavior in marble burying test. AVC (5 mg/kg) had no effect on all behavioral tests, while AVC (10 mg/kg) produced partial effects. It revealed anxiolytic-like effects of AVC. Furthermore, anxiolytic-like effects of AVC at higher doses (15–20 mg/kg) were more pronounced than lower doses (10 mg/kg) and were quite similar to the standard drug DIA. The present finding demonstrates, for the first time, the anxiolytic-like effects of AVC, which may be an alternative approach for management of anxiety-related disorders. & 2014 Elsevier B.V. All rights reserved. 1. Introduction Anxiety disorders are among the commonly occurring psychiatric illnesses imposing a prominent health care problem worldwide. Kessler et al. (2005) have reported that anxiety disorders have a lifetime prevalence of approximately 30% in the United States population. Anxiety disorders surface in a number of forms including panic disorders, post-traumatic stress disorders, obsessive–compul- sive disorders and phobias, which often share major physical and mental symptoms such as racing thoughts, nervousness, tremor, insomnia, emotional discomfort and agitation (Kalueff et al., 2007). Moreover, there is increasing clinical evidence that anxiety disorders also lead to suicidal attempts (Capron et al., 2012). Although several patients with anxiety disorders report significant relief of their symptoms with benzodiazepines (BDZ) like diaze- pam (DIA) and progressive recovery on continuous use of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Ravindran and Stein, 2010), these drugs are often associated with various side effects and delayed therapeutic effects (Chouinard, 2004; Ferguson, 2001; Periyakoil et al., 2005; Uzun et al., 2010). Moreover, despite consistent increase in anxiolytic drugs, the prevalence rate of this disorder is stable; this can be attributed at least in part to the inconsistent efficacy of current pharmacotherapy (Jindal et al., 2012). Thus, there is a grave need to explore novel targets and new agents with promising anxiolytic and fewer unwanted effects. Biochemical studies have revealed a prominent participation of a serotonin (5HT) system in pathogenesis of anxiety disorders (Akimova et al., 2009). 5HT pathways originating from raphe nuclei are widely innervated in corticolimbic structures such as hippocampus, amygdala and frontal cortex, where they play a major role in controlling mood and emotional behavior (Cubero et al., 2011). Notably, excessive 5HT stimulation may cause anxiety, while a decrease in 5HT neurotrans- mission may develop anxiolytic-like effects (Fedotova et al., 2004; Griebel et al., 2000). Based on the above observation, two approaches have been reported for the normalization of 5HT neurotransmission. Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/ejphar European Journal of Pharmacology http://dx.doi.org/10.1016/j.ejphar.2014.08.033 0014-2999/& 2014 Elsevier B.V. All rights reserved. n Corresponding author. Mobile: þ91 9352011573; fax: þ91 1596244183. E-mail addresses: deepaligupta2010@gmail.com (D. Gupta), rmaheshbits@gmail.com (M. Radhakrishnan), yashkurhe@gmail.com (Y. Kurhe). European Journal of Pharmacology 742 (2014) 94–101