[Comparative study of discriminative stimulus properties of antidepressants].

Interoceptive stimulus properties of amitriptyline (54 mg/kg body weight), fluoxetine (10 mg/kg), and pyrrolo[1,2-a][1,4]diazepine derivative GMAL-24 (10 mg/kg) were studied in a standard operant model with liquid reinforcement of drug discrimination (DD) in male Wistar rats. A new experimental schedule that includes subchronic (7-day) administration of a training drug was used to perform DD learning. For the first time, it was found that amitriptyline has a discriminative interoceptive stimulus properties. Neither fluoxetine nor GMAL-24 did exhibit interoceptive properties. Imipramine (15 mg/kg, i.p.) fully substitutes for amitriptyline stimulus in substitution test. Fluoxetine (5 - 20 mg/kg, i.p.) failed to substitute with amitriptyline. Thus, amitriptyline/saline drug discrimination should be used for a comparative analysis of the central mechanisms of action of psychotropic substances, rather than for screening specific antidepressant activity.

[Role of GABA-A receptors in mechanism of psychotropic action of pyrrol[1,2-a][1,4]diazepines studied using drug discrimination technique in Wistar rats].

The role of GABA-A receptors in psychotropic effects of pyrrolo[1,2-a][1,4]diazepine derivatives GMAL-24 and GMAL-27 has been studied on an operant method with liquid reinforcement of drug discrimination in male Wistar rats. It is established that, in substitution tests, GMAL-24 (2, 5, 10 mg/kg) and GMAL-27 (2, 5, 10 mg/kg) do not produce interoceptive effects of phenazepam (1 mg/kg) and fail to inhibit interoceptive effects of corasol (20 mg/kg). The obtained results indicate that pyrrolo[1,2-a][1,4]diazepine derivatives do not exhibit GABA-A receptor-positive modulator properties in vivo.

[Neurosteroidogenesis and exploratory responses in rodents].

We have studied the influence of intraperitoneal introduction of a selective blocker of mitochondrial translocation protein 18kD PK11195 (5 mg/kg), indomethacin (5 and 10 mg/kg), finasteride (5 and 15 mg/kg), and neurosteroid pregnenolone (20 mg/kg) on the exploratory behavior of male BALB/c mice, C57BL/6 mice, and Wistar rats in open-field test. It is found that treatment with PK11195 weakens the exploratory behavior in open-field test in mice of both strains. Finasteride and indomethacin decrease the exploratory responses in rodents regardless of the species or type of stress emotional response phenotype. Pregnenolone possesses activating effect in open-field in open-field test, but enhances the inhibitory effect of finasteride in BALB/c mice.