[Changes in the psychoemotional state under the influence of derivatives of neuroactive amino acids of rats after chronic alcohol intoxication]. / Izmenenie psikhoemotsional'nogo sostoyaniya pod vliyaniem proizvodnykh neiroaktivnykh aminokislot u krys posle khronicheskoi alkogol'noi intoksikatsii.

OBJECTIVE: To study an effect of neuroactive amino acids derivatives glufimet and mefargin on the psychoemotional state of rats after chronic alcohol intoxication (CAI). MATERIAL AND METHODS: The study was carried out on 10-month-old female Wistar rats. CAI was modeled by replacing drinking water with a 10% solution of ethyl alcohol sweetened with sucrose (50 g/l) for 6 months. Animals (age - 16 months) were divided into groups at the end of alcoholization: 1 (n=15) - intact group - rats without CAI; 2 (n=14) - control - females after CAI; 3 (n=11), 4 (n=14), 5 (n=11) and 6 (n=10) - experimental - females after CAI who received the GABA derivative mefargin (25 mg/kg), the glutamic acid derivative glufimet (29 mg/kg) and comparison drugs phenotropil (25 mg/kg) and heptral (100 mg/kg), respectively. Substances were administered to rats after 6 months of alcoholization intraperitoneally once a day for 14 days, the intact and control groups received physiological saline. The psychoemotional state of the animals was studied in the «Open field¼ test, «Elevated plus maze¼ test, «Marble burying¼ test and the Porsolt swim test after the treatment. RESULTS: In animals of the control group, an increase in anxiety was noted, as evidenced by a greater number of boluses in the Open Field test (3.43±0.56 vs. 1.47±0.39) compared to the intact group (p<0.05), short duration of stay in open arms (26.07±3.47 vs. 68.67±10.08) and fewer hangings from them (3.07±0.25 vs. 6.67±0.79) in the «Elevated plus maze¼ test. Rats after CAI buried more balls (8.79±1.15 versus 2.73±0.71, p<0.05), which indicated that they had compulsive behavior. In addition, females of the control group were observed to be depressed, as evidenced by a long period of immobilization in the Porsolt swim test (2.36±0.41 versus 0.87±0.31, p<0.05). CONCLUSION: Mefargin, glufimet, phenotropil and heptral restricted anxiety and manifestations of obsessive-compulsive disorder in females subjected to alcoholism (p<0.05). The antidepressant effect was observed in animals treated with phenotropil and heptral after CAI (p<0.05).

Comparison of Nootropic and Neuroprotective Features of Aryl-Substituted Analogs of Gamma-Aminobutyric Acid.

GABA analogs containing phenyl (phenibut) or para-chlorophenyl (baclofen) substituents demonstrated nootropic activity in a dose of 20 mg/kg: they improved passive avoidance conditioning, decelerated its natural extinction, and exerted antiamnestic effect on the models of amnesia provoked by scopolamine or electroshock. Tolyl-containing GABA analog (tolibut, 20 mg/kg) exhibited antiamnestic activity only on the model of electroshock-induced amnesia. Baclofen and, to a lesser extent, tolibut alleviated seizures provoked by electroshock, i.e. both agents exerted anticonvulsant effect. All examined GABA aryl derivatives demonstrated neuroprotective properties on the maximum electroshock model: they shortened the duration of coma and shortened the period of spontaneous motor activity recovery. In addition, these agents decreased the severity of passive avoidance amnesia and behavioral deficit in the open field test in rats exposed to electroshock. The greatest neuroprotective properties were exhibited by phenyl-containing GABA analog phenibut.

Functional aspects of neuroprotective effects of new salts and compositions of baclofen in the convulsive syndrome caused by electroshock.

New salts of baclofen (4-amino-3-(para-chlorophenyl)-butyric acid) and its compositions with organic carbonic acids (citric, succinic, malic, oxalic, nicotinic, glutamic acids and glycine) exhibited neuroprotective and anticonvulsive effects. They reduced the intensity of the convulsive syndrome and postconvulsive psychoneurological disorders in animals exposed to the maximum electroshock and electroconvulsive shock. Analogs of baclofen containing citrate and to a lesser extent those containing glutamate and glycine were significantly more active than the initial substance.

[Fenibut and its citrate prevent psychoneurological disorders caused by chronic stress (paradoxical sleep deprivation)].

The antistress protective action of two structural analogs of GABA, fenibut and its salt with citric acid (fenibut citrate, citrocard, RGPU-147), has been studied using a model of chronic stress caused by seven-fold 24-h deprivation of paradoxical sleep phase at an interval of 24 h between the deprivations. It is established that fenibut and fenibut citrate produce a protective action by (i) reducing the intensity of emotional disorders in the open-field test and elevated plus maze test, (ii) decreasing cognitive disorders in the tests for conditioned avoidance response and extrapolatory deliverance; and (iii) limiting stress reaction due to a decrease in the intensity of adrenal hypertrophy, thymus involution, and stomach mucous membrane ulceration. Fenibut citrate surpasses fenibut in the intensity of antistress protective action.

[Effect of phenibut on the content of monoamines, their metabolites, and neurotransmitter amino acids in rat brain structures].

Effects of the nootropic drug phenibut, which is a structural analog of gamma-aminobutyric acid (GABA), on the content of monoamines, their metabolites, and neurotransmitter amino acids in brain structures have been studied on Wistar rats. It is established that a single administration of phenibut in a dose of 25 mg/kg (i.p.) produces a statistically significant increase in the content of dopamine metabolite (3,4-dioxyphenylacetic acid) and the retarding amino acid taurine in striatum. At the same time, phenibut did not significantly influence the levels of GABA, serotonin, and dopamine in various brain structures and produce a moderate decrease in the level of norepinephrine in the hippocampus.

[Effect of phenibut on interhemispheric transmission in the rat brain].

Effects of the nootropic drug phenibut on the transcallosal potential amplitude in the sensomotor brain cortex have been studied in rats. It is established that a single administration of phenibut in a dose of 25 mg/kg (i.p.) increases the transcallosal response amplitude, thus improving the interhemispheric transmission. This effect, being an objective evidence of the nootrope activity, confirms the drug status and corroborates the positive action of phenibut on the learning and memory processes.

[Comparative evaluation of the neuroprotective activity of phenibut and piracetam under experimental cerebral ischemia conditions in rats].

The neuroprotective properties of phenibut and piracetam were studied in rats with cerebral ischemia caused by bilateral irreversible simultaneous occlusion of carotid arteries and gravitational overload in craniocaudal vector. In addition, the effects of both drugs on microcirculation in brain cortex under ischemic injury conditions were studied. Phenibut and (to a lower extent) piracetam reduced a neuralgic deficiency, amnesia, and the degree of cerebral circulation drop, and improved the spontaneous movement and research activity deteriorated by brain ischemia.

[Effect of phenibut on the behavior of experimental animals under conditions of voluntary chronic alcoholism].

The effect of phenibut on the locomotor and orientation-research activity, as well as on the alcohol and food motivation, was studied on experimental animals under conditions of voluntary chronic alcoholism. Phenibut decreased the manifestations of alcohol-induced behavioral disorders and reduced alcohol motivation.