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.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Borovikov VP. Statistica: Art Analysis of the Data on the Computer: For professionals. St. Petersburg, 2003. Russian.
Kaluev AV, Nutt DJ. On the role of GABA in anxiety and depression. Eksp. Klin. Farmakol. 2004;67(4):71-76. Russian.
Korolev AO, Kalinina TS, Volkova AV, Mokrov GV, Kudryashov NV, Voronina TA. Comparative Study of Discriminative Stimulus Properties of Antidepressants. Eksp. Klin. Farmakol. 2014;77(7):3-7.
Belelli D, Lambert JJ. Neurosteroids: endogenous regulators of the GABA(A) receptor. Nat. Rev. Neurosci. 2005;6(7):565-675.
Girdler SS, Klatzkin R. Neurosteroids in the context of stress: implications for depressive disorders. Pharmacol. Ther. 2007;116(1):125-139.
Korpi ER, Gründer G, Lüddens H. Drug interactions at GABA(A) receptors. Prog. Neurobiol. 2002;67(2):113-159.
Kudryashov NV, Kalinina TS, Shimshirt AA, Korolev AO, Volkova AV, Voronina TA. Antidepressant-like effect of fluoxetine may depend on translocator protein activity and pretest session duration in forced swimming test in mice. Behav. Pharmacol. 2018;29(4):375-378. doi: https://doi.org/10.1097/FBP.0000000000000359
Malatynska E, Crites G, Yochum A, Kopp R, Giroux ML, Dilsaver SC. Schild regression analysis of antidepressant and bicuculline antagonist effects at the GABAA receptor. Pharmacology. 1998;57(3):117-123.
Malatynska E, Dilsaver SC, Knapp RJ, Giroux ML, Ikeda M, Yamamura HI. The interaction of a benzodiazepine receptor antagonist (Ro15-1788) with GABA and GABA receptor antagonists at the GABA(A) receptor chloride-ionophore complex. Neurochem. Int. 1991;18(3):405-410.
Malatynska E, Miller C, Schindler N, Cecil A, Knapp A, Crites G, Rogers H. Amitriptyline increases GABA-stimulated 36Clinflux by recombinant (alpha 1 gamma 2) GABAA receptors. Brain Res. 1999;851(1-2):277-280.
Möhler H. The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology. 2012;62(1):42-53.
Morrow AL, Suzdak PD, Paul SM. Steroid hormone metabolites potentiate GABA receptor-mediated chloride ion flux with nanomolar potency. Eur. J. Pharmacol. 1987;142(3):483-485.
Uzunova V, Sampson L, Uzunov DP. Relevance of endogenous 3alpha-reduced neurosteroids to depression and antidepressant action. Psychopharmacology (Berl). 2006;186(3):351-361.
Wettstein JG, Gauthier B. Discriminative stimulus effects of alprazolam and diazepam: generalization to benzodiazepines, antidepressants and buspirone. Behav. Pharmacol. 1992;3(3):229-237.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 168, No. 9, pp. 308-312, September, 2019
Rights and permissions
About this article
Cite this article
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). https://doi.org/10.1007/s10517-020-04704-0
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10517-020-04704-0