Russian Journal of PhysiologyRussian Journal of PhysiologyРоссийский физиологический журнал им. И.М. Сеченова0869-81392658-655XThe Russian Academy of Sciences65174810.31857/S0869813924090095AJSTYGEXPERIMENTAL ARTICLESЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИResearch ArticleD-serine reduces extracellular serotonin level in the medial prefrontal cortex and enhances the formation of fear response in ratsD-серин снижает уровень внеклеточного серотонина в медиальной префронтальной коре и усиливает формирование реакции страха у крысSaulskayaN. B.СаульскаяН. Б.
Russian Federation
saulskayanb@infran.ruSusorovaM. A.СусороваМ. А.
Russian Federation
saulskayanb@infran.ruPavlov Institute of Physiology, Russian Academy of SciencesИнститут физиологии им. И.П. Павлова Российской академии наук1509202411091406141902022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-8139/article/view/651748

D-serine is an endogenous agonist of the glycine site of NMDA receptors. However, its contribution to the medial prefrontal cortex (mPFC) functions has been little studied. The purpose of the work was to study the involvement of D-serine in the mPFC in the formation and generalization of the conditioned fear response (CFR – a fear model), as well as in the regulation of serotonin release in this area. In Sprague-Dawley rats by means of in vivo microdyalisis and HPLC analysis, we showed that the intra-mPFC infusion of D-serine (1 mM) reduces the basal level of extracellular serotonin in this area and decreases its rise during CFR acquisition (pared presentation of a conditioned cue (CS+) and inescapable footshock but not during differentiation 1 (presentation of a differentiation cue (CS-) alone).The intra-mPFC D-serine infusion reduced animals’ freezing to CS+ (a measure of passive footshock anticipation) during the CFR acquisition and increased ambulation and the number of rearing (attempts to escape footshock). This pharmacological treatment, a day after it, increased animals’ freezing to the potentially dangerous CS+, but did not affect freezing to the safe CS-. The data obtained indicate for the first time that, with a decrease in the release of serotonin in the mPFC, stimulation of the mPFC by D-serine enhances the animals’ active strategy of avoiding shock and suppresses the passive strategy of anticipating it.

This is accompanied by increased acquisition and/or consolidation of the CFR, but does not affect its generalization.

D-серин является эндогенным агонистом глицинового сайта NMDA-рецепторов. Однако его вклад в организацию функций медиальной префронтальной коры (мПК) исследован мало. Целью работы было изучение участия D-серина в мПК в формировании и генерализации условной реакции страха (УРС – модель страха), а также в регуляции выброса серотонина в этой области. На крысах линии Спрег-Доули методами прижизненного внутримозгового диализа и ВЭЖХ показано, что введение D-серина (1мМ) в мПК снижает в ней базальный уровень внеклеточного серотонина и уменьшает на фоне такого снижения рост данного показателя во время выработки УРС (сочетание условного сигнала (CS+) с неизбегаемым болевым раздражением), но не в ходе дифференцировки 1 (предъявление дифференцировочного сигнала (CS–) без болевого раздражения). Введение в мПК D-серина уменьшало во время выработки УРС замирание животных на CS+ (показатель пассивного ожидания болевого раздражения) и увеличивало горизонтальную двигательную активность и число стоек (попытки избежать болевого раздражения). Такое фармакологическое воздействие приводило через сутки к усилению замирания на потенциально опасный CS+, но не на безопасный CS–. Полученные данные впервые свидетельствуют, что D-сериновая стимуляция мПК, снижающая выброс серотонина в этой области, усиливает в ходе выработки УРС активную стратегию поведения животных, направленную на избегание, и тормозит пассивную стратегию ожидания болевого раздражения. Это сопровождается усилением формирования и/или консолидации УРС, но не влияет на ее генерализацию.

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