Abstract
To study the mechanisms of the action of neuroglutam (beta-phenylglutamic acid hydrochloride, RGPU-135), which is a drug with antidepressant and anxiolytic activities, we examined the influence of the antagonist of GABAA receptors bicuculline (1 mg/kg) and the antagonist of GABAB receptors phaclofen (2 mg/kg) on the type and strength of the effects of neuroglutam (26 mg/kg) in behavioral tests. Anxiolytic effects were examined in the open-field test and dark–light box; antidepressant effects were examined in the tail-suspension test. During combined treatment with neuroglutam and bicuculline, anxiolytic and antidepressant effects of neuroglutam did not occur, i.e., development of these effects requires activation of GABAA receptors. Phaclofen counteracted the antidepressant effect of neuroglutam, which, to a certain degree is related to activation of GABAB receptors. Neuroglutam (26–650 mg/kg) suppressed seizures that were induced by the blockers of GABAA receptors picrotoxin (5 mg/kg) and pentylenetetrazol (90 mg/kg), which reflects its capacity to influence this channel. Analysis of the neuroglutam influence (10–10–10–4 M) on the rat brain GABAA and GABAB receptors by the method of radioligand binding in vitro using tritiated [G3-H]SR95531 (for GABAA) and [G3-H](-)Baclofen (for GABAB receptors) did not reveal direct interaction of neuroglutam with these receptors. Subchronic systemic administration of neuroglutam (26 mg/kg, daily for 5 days) to rats induced an increase in the density of GABAA receptors in the prefrontal cortex, which points to its capacity to modulate the expression of GABAA receptors. These data suggest that one of the aspects of the neuropsychotropic effects of neuroglutam is interaction with the GABAergic neurotransmitter system.
Published Version
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