Assessment of Susceptibility of Outbred Albino Rats to the Formation of Depression-Like State of Learned Helplessness.

Learned helplessness (a model of depression-like state) was developed in rats by exposure to repeated inescapable electric stimulation and evaluated by the absence of attempts to escape when it could be performed. In randomly grouped outbred white rats, 37.5% animals after the above procedure meet the criterion of learned helplessness. On experimental day 14, the latent period and the number of applied electric shocks prior to the first escape to the safe compartment in rats with learned helplessness were significantly higher than in the control, but no significant differences in these parameters were observed on day 21. The Porsolt forced swimming test performed on days 14 and 21 revealed no differences from the control group. After the rats were divided into low- and high-active subgroups according to their open field behavior, 35% rats with learned helplessness were in the low-active subgroup group and 30% rats with learned helplessness were in the high-active subgroup. On day 14, the parameters of learned helplessness significantly surpassed the control levels only in the low-active subgroup. Only in rats with learned helplessness and low activity in the open field, the immobility time in the Porsolt test was longer than in control low-active rats. These findings attest to advisability of preliminary splitting of outbred animals by their open-field behavior into low- and high-active subgroups and the use of only animals for modeling learned helplessness.

[Effect of afobazole and levodopa on the activity of proline-specific proteinases and adenosine deaminase in blood serum and brain structures of rats with experimental Parkinson's syndrome induced by systemic administration of rotenone]. / Vliianie afobazola i levodopy na aktivnost' prolinspetsificheskikh proteinaz i adenozindezaminazy v syvorotke krovi i strukturakh golovnogo mozga krys s éksperimental'nym parkinsonicheskim sindromom, vyzvannym sistemnym vvedeniem rotenona.

Rats with experimental Parkinson's syndrome induced by seven-day intraperitoneal administration of rotenone at a dose of 2.75 mg/kg have an increased activity of prolylendopeptidase (EC 3.4.21.26, PREP) in blood serum and a decreased activity of adenosine deaminase (EC 3.5.4.4, ADA) in serum and in the prefrontal cortex. PREP and ADA activity in other brain structures (in the striatum, hypothalamus and hippocampus) did not change; dipeptidyl peptidase IV activity (EC 3.4.14.5, DPP-4, CD26) also remained constant in serum and in all the brain structures investigated. Afobazole and levodopa, which exhibit antiparkinsonian activity in this model of Parkinson's syndrome, decrease elevated PREP activity in serum and increase reduced ADA activity in the prefrontal cortex of rats with the experimental pathology. Meanwhile, treatment with the study drugs was associated with a decrease of ADA activity in the other brain structures.

[COMPARISON OF CYTOPROTECTIVE EFFECTS OF HEMANTANE AND AMANTADINE UNDER CONDITIONS OF 6-HYDROXYDOPAMINE NEUROTOXIN ACTION ON CULTURED HUMAN NEUROBLASTOMA CELLS].

Potential neuroprotective activity of the novel antiparkinsonian drug hemantane (hydrochloride N-2-(adamantyl)-hexamethylenimine) in comparison to amantadine has been studied in various regimes of administration on human neuroblastoma SH-SY5Y cell line injury induced by 6-hydroxydopamine (6-OHDA), which is used as in vitro model of dopaminergic neurons for Parkinson's disease. Two regimes of hemantane and amantadine administration in a range of final concentrations 10⁻6-10⁻8 M were used either prior to or immediately after 6-OHDA introduction. MTT colorimetric assay was used to assess the viability of test cells. Significant decrease in viability of SH-SY5Y cells treated with 6-OHDA was observed. The addition of hemantane to cell medium produced cytoprotective effects in both regimes of administration--before and after 6-OHDA--at concentrations 10⁻7 M and 10⁻6-10⁻8 M, respectively. Amantadine in con- centrations 10⁻7-10⁻8 M was effective to increase cell survival only when administered after 6-OHDA. These results show that hemantane has a greater neu-roprotective potential in comparison to amantadine.