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.

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Correspondence to A. O. Korolev.

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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 168, No. 9, pp. 308-312, September, 2019

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Korolev, A.O., Kalinina, T.S., Volkova, A.V. et al. Role of GABAA Receptors in the Mechanism of In Vivo Psychotropic Activity of Amitriptyline in Rats. Bull Exp Biol Med 168, 341–344 (2020).

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Key Words

  • drug discrimination
  • GABAA receptors
  • tricyclic antidepressant
  • amitriptyline
  • rats