PECULIARITIES OF LEARNING IN RATS WITH ACUTE AND CHRONIC EPILEPTIC SYNDROME UNDER CONDITIONS OF PITOLISANT ADMINISTRATION

The study of neuropathophysiological mechanisms of epileptic activity that occur with the participation of the brain’s endogenous histaminergic system makes it possible to substantiate effective, complex means of controlling seizure manifestations and comorbid conditions, including cognitive impairment. Objective – to investigate the state of cognitive functions in models of PTZ-induced kindling and maximal electroconvulsive seizures (MES) against a background of pitolisant administration. Material and Methods. Kindling syndrome was induced in Wistar rats by daily administration of pentylenetetrazole (PTZ) (35.0 mg/kg, i. p.) for three weeks. In the tests of active avoidance and recognition of new objects, behavioral parameters were studied under the conditions of pitolisant administration (0.5 and 3.0 mg/kg, i. p.), which were compared with MES-induced disorders. Results. The number of sound signals to which active avoidance reaction was observed in rats with MES was 5.7 times less than in the control (P<0.05). The pitolisant (0.5 mg/ kg, i. p.) increased the studied index 52.2% (P<0.05), and at a dose of 3.0 mg/ kg, i. p. – 73.1% (P<0.05) compared to the baseline. In rats with PTZ-kindling, the studied index was 59.8% lower than in control (P<0.05). Against the background of pitolisant administration at a higher dose (3.0 mg/kg, i. p.), the number of sound signals to which active avoidance reactions were observed was 6.92+0.71. It was 49.4% higher than in rats with developed PTZ-kindling (P<0.05). The discriminative index (DI) of rats with MES was lower than that of the control 47.7% (P<0.05) and amounted to 33.21+3.14 units (U). The DI against a background of pitolisant (3.0 mg/kg, i. p.) exceeded the index in rats with MES 35.4% (P<0.05) and was less than in the control 25.4% (P<0.05). In rats with PTZ-kindling, the DI was 41.27+2.93 U and was 35.0% less than in the control (P<0.05). Against the background of the use of pitolisant at a dose of 3.0 mg/kg, the DI exceeded that in the group of kindling rats 32.7% (P<0.05) and did not differ from the control group (P>0.05). Conclusions. The severity of cognitive impairment in PTZ-kindling rats is less than in rats with MES. Cognitive impairment in rats after the seizure period is corrected using pitolisant, indicating histamine-dependent pathogenesis mechanisms.