We have examined seleptine, a new derivative of the atypical neuroleptic clozapinum, on the retrieval of the active avoidance task in rats placed in a shuttlebox. Retention of the conditioned response was assessed in the test of repeated training for the same task to the score achieved in the first session. After oral seleptine (100 mg/kg), the retention of the active avoidance task was deteriorated to a greater extent than the ability for a new learning.Key Words: seleptine; neuroleptics; avoidance response As all conditioned responses (CR) developed by negative reinforcement, two-way active avoidance (AA) in a shuttlebox is controlled by endogenous substances that determine the emotion-motivational status of experimental animals [3]. Logically, chemical agents that decrease motivation level of response (neuroleptics and tranquilizers) impede learning and disturb consolidation of the memory trace [1]. Our aim was to study the effect of the putative tran-a new structural analog of clozapinum (azaleptine, an atypical benzodiazepine neuroleptic), on retention and repeated training for the conditioned active avoidance response (CAAR). MATERIALS AND METHODSMale Wistar rats with (body weight 230-260 g) were trained for CAAR in the shuttlebox of a Reflex-6 system (Columbus Instruments Inc.). The rats were trained for AA task by the modified method [4] to 10 successive correct avoidance responses. The conditioned stimulus was a 5-sec tone. The unconditioned stimulus was a footshock with the strength Institute of General Pathology and Pathological Physiology, Russian Academy of Medical Sciences, Moscow tuned individually for each rat. The period of combined presentation of conditioned and unconditioned stimuli was no longer than 15 sec; the interval between the combined stimuli was 20-40 sec. During a single session the rats were subjected to no more than 40 footshocks. If this criterion was not achieved, the rat was discarded. Only 61% of the tested rats acquired this reflex.The state of the temporal connection was assessed according to the retrieval of AA task after the second session: 7 days after acquisition of CAAR the rats were trained to the same score of 10 successive correct responses. Retention (R) of CR was calculated from the following formula R=(A-B)/A• 100%, where A and B are the numbers of combined stimuli presented to develop CR in the first and second session, respectively. Seleptine was synthesized at the Novokuznetsk Chemical-Pharmaceutical Institute. Water solution of seleptine (10, 30, and 100 mg/kg) was administered orally 30 or 60 rain prior to the second training session for CAAR. The total volume of liquid was no more than 0.5 ml. During the same period the control rats were treated with 0.5 ml saline. Each rat was tested only once, every group consisted of 7 rats. The results were statistically analyzed using nonparametric one-factor analysis for independent variants (Kruskal-Wallis test).

The neuroleptic azaleptine and its new derivative seleptine with anticonvulsive properties were examined in a chronic experiment on rabbits for their comparative effects on the spontaneous electroencephalogram (EEG) and the activation reaction in the sensorimotor cortex and dorsal hippocampus. Azaleptine induced synchronization of electroencephalographic activity in all frequency ranges of both cortical and hippocampal EEGs, while seleptine induced desynchronization in the. cortical EEG and synchronization in the 5, 0, and I~ ranges of the hippocampal EEG. Both compounds prevented the activation or altered its pattern, leading to a decrease in the power of the 13 range rather than increasing it as is normally observed.Key Words: azaleptine; seleptine; neuroleptics; anticonvulsants; total electroencephalogram; activation reaction, which has been successfully used in medical practice, is a typical neuroleptic with a unique neuropharmacological profile [4,8]. Its new structural analog seleptine (8-chloro-11-(4-methyl-1-piperazinyl)-5-acetylaminodibenzo-[b,e][1,4]-diazepine) is regarded as a potential anticonvulsant with possible psychotropic properties.In this study on rabbits, we compared the effects of the two compounds on spontaneous electric activity of the sensorimotor cortex and dorsal hippocampus as a test for alterations in the general excitability of the brain and in the functional status of neurotransmitter systems. MATERIALS AND METHODSThis chronic experiment was carried out on rabbits (bodyweight 2.3-3.5 kg), 6 animals in each group, implanted stereotaxicaUy with bipolar nichrome electrodes under Nembutal anesthesia (30 rag/ kg after Aminazine [chlorpromazine] administration). The recording electrodes were implanted into the sensorimotor area of the neocortex (AP 2-3; L 2; H 2) and into area CA3 of the dorsal hippocampus (AP 5.5-7; L 5.2-6.5; H 3.5), the stimulating electrodes were implanted into the mesencephalic part of the reticular formation (nucleus cuneiformis, pars dorsalis; AP 13.5; L 2.4; H 7), while the indifferent electrodes were placed in the nasal bone and over the visual cortex in the occipital bone. Tests were started 5-7 days postimplantation.The total electroencephalogram (EEG) was recorded bipolarly in nonrigidly fixed animals in a shielded soundproof darkened chamber. The EEG