Semax prevents functional impairments of avoidance response in rats

Abstract

ACTH/MSHrelated peptides, known as melanocortins, play an important role in regulation of manyfunctions in the body, including CNS. Among melanocortins, Semax is very prominent because it is anootropic analogue of ACTH (4–10) with prolongedaction [1]. In experiments with animals, the beneficialeffects of Semax on learning with positive reinforcement have been repeatedly reported [2]. Data on theSemax effects on animal learning with negative reinforcement are very few and contradictory. Data onboth learning improvement [3] and no effect [4] havebeen published.Mixed effects of nootropic drugs on learning arewell known [5, 6]; therefore, different approachesimpairing learning and memory, such as maximalelectroshock, ischemia or frontal lobectomy [7] areused for study of nootropic properties of substances.We suppose that use of models without any excessivemethodical complications and extreme physical treatment is very promising. For this purpose, functionalimpairments of the conditioned response of activeavoidance of pain stimulation in rats were suggested[8]. They are based on modification of definite cause–effect, i.e., “avoidance response failure,” and spatialrelationships in experimental environment.Here, we studied the effects of Semax on the development of avoidance conditioning in rats and its functional impairments modeled using failure and spatialmodification approaches.MATERIALS AND METHODSTwentysix male outbred albino rats weighing 250–370 g were used for the experiment. The animals weredaily trained for active avoidance conditioning in ashuttlebox for 7 days. Each daily session consisted of25 stimulus presentations. A shuttlebox was equippedwith a partition with two doors. During training, thedistal door in the partition was opened. The followingprotocol was used for training: a rat was placed into acompartment of the shuttlebox, the conditionedstimulus (tone) was presented, and, 10 s later, theunconditioned stimulus (electroshock) was presented.Crossing to the opposite compartment in response tothe conditioned stimulus was regarded as a conditioned avoidance response. Daily, we recorded thenumber of avoidances and expressed them as percentof the total number of stimulus presentations. On thelast day of training, we used the protocol of avoidancefailure after 20 stimulus presentations. For this purpose, during 5 last stimulus presentations, we did notturn off stimuli when the rat crossed to another compartment in response to conditioned or unconditionedstimuli, and it was subjected to electroshocks. After thefifth presentation, electroshock was stopped immediately, whereas the tone was turned off 2 s later. Then,20 presentations were used for testing of avoidanceresponse under the initial conditions. Since behavioralchanges appeared immediately after functionalimpairment, we analyzed the time course of changesin the indices of avoidance conditioning in blocks of 5presentations.Failure is reversible functional impairment thatallows using the same animals to study consequentlythe effects of nootropics under the conditions of oneand the other model and to obtain a reproducible nootropic effect [9]. Based on this assumption, we reproduced avoidance response one day after its failure.Then we closed the distal door, opened the proximaldoor, and tested avoidance response recall under newconditions during 20 stimuli presentations.Thirty minutes prior to each experiment, we intraperitoneally injected a Semax solution at a dose of0.05 mg/kg in a volume of 1 mL/kg. Control animalswere injected with an equal volume of distilled water.Data in figures are presented as the means andstandard errors.