D.F. Avgustinovich, T.G. Tolstikova

In the present study we determined effects of combined administration of the widely clinically used anxiolytic buspirone (0.05 mg/kg and 1 mg/kg; Sigma Chemical Co., USA), which is a partial agonist of 5-НТ1А receptors, and phenibut (25 mg/kg, Shenzhen Meredian Investment Co. Ltd, China), a GABAB receptors agonist. The objective was set to determine presence or absence of phenibut-s influence on buspirone-s effect as estimated by the animals - behavior. The experiments were performed on male mice of the C57BL/6J strain, being 3 months of age and having body weights of 24-27 g. The animals were placed one per experimental cage with the dimensions 28х14х10 cm, and 3.5 days later in the second part of the day (3.00 - 6.00 p.m.) the acute administration effects of phenibut and buspirone on the mice-s behavior were determined in the plus-maze test, a standard anxiety test. The following groups of mice were studied: «control1» - animals receiving an intraperitoneal injection of the saline30 minutes before the test; «buspirone0.05» - animals receiving an intraperitoneal injection of 0.05 mg/kg buspirone 30 minutes before the test; «buspirone1» - animals receiving an intraperitoneal injection of 1.0 mg/kg buspirone 30 minutes before the test; «control2» - per os administration of the saline + intraperitoneal injection of the saline 30 minutes after the first administration and half an hour before the test; «phenibut» - per os administration of 25 mg/kg phenibut + intraperitoneal injection of the saline 30 minutes after the first administration and half an hour before the test; «phenibut+buspirone0.05» - per os administration of 25 mg/kg phenibut + intraperitoneal injection of 0.05mg/kg buspirone 30 minutes after the first administration and half an hour before the test; «phenibut+buspirone1» - per os administration of 25 mg/kg phenibut + intraperitoneal injection of 1.0 mg/kg buspirone 30 minutes after the first administration and half an hour before the test. As the study demonstrated, the injections of both buspirone doses had no effect on behavior of the mice in the plus-maze test: the mice injected with buspirone did not differ from the mice injected with the saline by any parameters under investigation. However, the higher buspirone dose (1 mg/kg), as compared to the lower one (0.05 mg/kg), somewhat decreased locomotor activity, which was assessed by the total number of entries into and exits from the arms. Phenibut had no independent effect on the parameters of the mouse behavior in the maze, either. And yet, combined administration of both drugs - phenibut and buspirone - altered behavior of the mice in the elevated plus-maze test significantly. In this case buspirone-s effect was apparent even at the small dose (0.05 mg/kg), at which the number of head dipping decreased. While at the higher buspirone dose (1 mg/kg) 6 out of 9 estimated maze parameters changed. Thus, the conducted study revealed absence of any effects of separate acute administration of buspirone or phenibut, as well as presence of an expressed dose-dependent effect of buspirone on the behavioral parameters in the animals preliminarily receiving phenibut. The revealed fact that phenibut potentiates buspirone-s effect is of principal importance as it demonstrates one of practicable methods of increasing the anxiolytic-s effectiveness along with dose reduction.