Interactions of antidepressants and ethanol on spontaneous locomotor activity and rotarod performance in NMRI and C57BL/6 mice

Abstract

In order to find appropriate doses for studying antidepressant-ethanol interaction in two mouse strains, spontaneous locomotor activity and rotarod performance were first studied in NMRI mice after amitriptyline 3-30 mg/kg, mianserin 3-30 mg/kg, nomifensine 1- 10 mg/kg, citalopram 3-100 mg/kg, and ethanol 1-3 g/kg intraperitoneally. Ethanol increased significantly locomotor activity at 1 g/kg and impaired rotarod performance at 2 and 3 g/kg. Amitriptyline and mianserin decreased dose-dependently locomotor activity at doses ≥ 10 mg/kg. Nomifensine and citalopram increased locomotor activity at 10 mg/kg and citalopram 100 mg/kg decreased it. Rotarod performance was affected only by amitriptyline 10 and 30 mg/kg and citalopram 100 mg/kg, which impaired performance. Interaction studies with the two strains using amitriptyline, mianserin, nomifensine and citalopram 10 mg/kg and ethanol 1 g/kg showed that C57BL/6 mice were less sensitive than NMRI mice to the stimu lating effects of ethanol and more sensitive to impairment of rotarod performance by amitrip tyline and mianserin. C57BL/6 mice had a significantly poorer baseline performance on rotarod, and the citalopram plus ethanol combination impaired their performance severely, although drugs alone did not impair this test. The results suggest that decreased locomotor activity as a measure of antidepressant-induced sedation does not parallel with impaired performance on rotarod and that significant strain differences can be seen in psy chopharmacological tests and responses to drugs in mice.