CORRECTION OF CONSEQUENCES OF NEONATAL ALGESIC AND STRESS STIMULATIONS OF ADULT RATS WITH BUSPIRONE

Abstract

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Neonatal and prepubertal periods of the development are characterized with hypersensibility to the environmental effects. Repetitive sensations of pain in a neonatal peri-od are the risk factor for the further development and functioning of not only no-ciceptive system, but also other systems of an organism, and the formation of different types of adaptive behavior. Serotonergic system and its receptors of 5-HT1A type play one of the principal roles in these processes. The purpose of the work was to study the influence of 5-HT1A agonist of buspirone receptors in a pubertal period of development on the adaptive behavior (painful response, psychoemotional behavior, anxiety and depressiveness level) of adult rats, exposed to the pain and/or stress stimulation in different terms of neonatal period. Materials and methods of the study: male and female Wistar rats on the first and again on the second day of their life or on the seventh and on the eighth day were exposed to the following stimulations: complex stimulation - pain with inflammation (intradermal injection with 2.5% of 0.5 μl formalin solution into the foot of a hindleg), and then stress stimulation by separation from their mother for 60 min, only pains with inflammation without separation from their mother, injection of physiological solution with separation from their mother, injections of physiological solution only. Chronic administration of 5-HT1A agonist of buspirone receptors (buspirone hydrochloride, Sigma, 3.5 mg/kg abdominally) was carried out from the 25th postnatal day during two weeks (prepubertal period of development). After growing up to 90 days rats were examined for a functional state of nociceptive system in the conditions of newly developed inflammation in a formalin test, the anxiety level in the “elevated plus maze” test, the level of tendency to a depression-like behavior in a forced swimming test, and the ability to regional differentiation in the Morris maze. Results: formalin test has revealed the intensification of a pain response of adult animals exposed to the inflammation pain on 1-2 day and separation from mothers of male rats, only stress for female rats, and in female rats exposed to the pain stimulation on 7-8 day. Chronic injection of buspirone leveled hyperalgesia in adult male and female rats in the formalin test, comparing with hyperalgesia in control animals. Data obtained in other behavioral tests points on the dependence of long-term influences of neonatal effects on the term of a neonatal period, in which the animals were exposed to the influence, type of influence and a unit gender, and also on the normalization of the studied indices to the chronic injection of buspirone. Conclusions: thus, the pain of inflamma-tion on the 1-2 day and 7-8 day of life provokes hyperalgesia in animals in the conditions of newly developed inflammation only in male rats, while the stress of separation from their mother on the 1-2 day provokes hyperalgesia in adult rats of both sexes. Chronic administration of buspirone in prepubertal period normalizes a pain sensibility of adult rats, which were ex-posed to the pain as well as to stress stimulation in a neonatal period. The results obtained give evidence about the fact that the buspirone administration in critical prepubertal period of development allows correction of the disorders provoked by neonatal pain and stress stimu-lations in nociceptive system, psychoemotional behavior, and cognitive sphere.