PHARMACOLOGICAL EVALUATION OF ANXIOLYTICS AND NICOTINE FOR ANXIETY-RELATED BEHAVIORS AND NEURONAL ACTIVITIES

Abstract Background Anxiety is frequently comorbid with peripheral as well as neuropsychiatric diseases. To alleviate the comorbid anxiety, anxiolytics are prescribed, and some people take nicotine through smoking. However, the physiological mechanism of anxiety and how anxiolytics and nicotine relieve it are not well known. Aims & Objects: To elucidate them, we performed a pharmacological evaluation of anxiolytics (diazepam, fluvoxamine, and tandospirone) and nicotine for the anxiety-related behaviors. Method The anxiety-related behaviors were evaluated in the marble burying test (MB), elevated plus-maze test (EPM), social interaction test (SIT), and novelty suppression feeding test (NSF) in an illuminance- dependent manner. Results Under the high anxiety illumination, diazepam showed anxiolytic effects on MB, SIT, EPM, and NSF. Fluvoxamine showed anxiolytic effect on MB. Tandospirone showed anxiolytic effects on MB and EPM. Nicotine showed anxiolytic effects on SIT and NSF. To evaluate the effect of anxiolytics and nicotine on the anxiety-related neuronal activity, we measured behavior-related immediate early gene (Arc) expression. Diazepam decreased EPM-related Arc expression in the amygdala but not the prefrontal cortex. However, nicotine did not affect SIT-related Arc expression in the amygdala and the prefrontal cortex. Discussion & Conclusion Since diazepam is a positive allosteric modulator of the GABAA receptors, our data suggest that diazepam shows anxiolytic effects on the various behavioral tests by suppression of neuronal activity in the amygdala through GABAergic receptors. Fluvoxamine and tandspiron are a selective serotonin reuptake inhibitor and a 5-HT1A receptor agonist, respectively. Our data suggest fluvoxamine and tandospirone show anxiolytic effect on MB via activation of 5-HT1A receptor. Interestingly, nicotine shows anxiolytic effects on SIT without change of neuronal activity in the amygdala and the prefrontal cortex. The anxiolytic effects of anxiolytics and nicotine were found to be specific to behavioural tests. More detailed assessment of neural activity in different tests will clarify their behavior-specific anxiolytic effects.