Role of GABAA Receptors in the Mechanism of In Vivo Psychotropic Activity of Amitriptyline in Rats.

Standard water-reinforced drug discrimination model was employed to train Wistar rats to discriminate the intraperitoneal injections of tricyclic antidepressant amitriptyline (5.4 mg/kg) and physiological saline. To examine the role of GABAA receptors in psychotropic action of amitriptyline, the substitution tests were performed with muscimol (0.1-1.0 mg/kg) and pregnenolone (30-50 mg/kg). Similar tests were carried out with amitriptyline interoceptive antagonists bicuculline (1 mg/kg), flumazenil (15 mg/kg), finasteride (5 mg/kg), and indomethacin (7.5 mg/kg). The study showed that interoceptive effects of amitriptyline depend on functional activity of GABAA receptors but not on the neurosteroid site of GABAA receptor complex.