The protective effects of a new low-molecular-weight mimetic of nerve growth factor hexamethylene diamide bis-(N-monosuccinyl-L-glutamine-L-lysine; GK-2) were studied on the experimental model of hemorrhagic stroke (intracerebral posttraumatic hematoma) in rats. Intraperitoneal injections of GK-2 in a dose of 1 mg/kg 4 and 24 h after surgery and 24 h before testing the CNS function on days 3, 7, and 14 prevent death of experimental animals, reduce the neurological deficit, and normalized behavior.
The antidepressant activity of the GSB-106, dipeptide mimetic of the 4th loop of BDNF, during long-term use was studied in doses of 1.0 mg/kg and 5 mg/kg for. When comparing antidepressant activity in the “forced swimming Porsolt test” on the 14th and 28th day of administration, it was established that the antidepressant effect did not change. It was shown that a withdrawal of prolonged administration for 28 days did not lead to an increase in anxiety in the “elevated plus-maze test” and to the development of disturbances in the exploratory behavior of animals and motor activity in the “open field” test. It was concluded that during long-term administration of GSB-106 the tolerance for the main antidepressant effect did not developed, and cessation of long-term administration of GSB-106 did not lead to the development of withdrawal syndrome. (For citation: Garibova TL, Krayneva VA, Valdman EA, et al. The study of the effects of dipeptide mimetic of a brain derived neurotrophic factor with antidepressant activity during prolonged use and after withdrawal. Reviews on Clinical Pharmacology and Drug Therapy. 2018;16(1):28-33. doi: 10.17816/RCF16128-33).
The “learned helplessness” (LH) model in rats is widely used in a battery of tests to assess depression-like behaviour and the effects of antidepressants. The model is considered to be suffi ciently valid, though having some limitations with reproducibility. This review discusses the possibilities of using the model for assessing the symptoms of a depressive-like state and the pathogenesis of depression, as well as the effects of antidepressants. The factors affecting the reproducibility of the LH model are described, the most important of which is the different sensitivity of animals to stress. Several protocols for the induction and testing of LH, which are used by different research teams, are presented. Due to the diffi culty of comparing the results obtained using different LH protocols, LH models should be standardized for use in individual laboratories. LH models are worth using in preclinical studies of potential drugs exhibiting antidepressant activity.
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