Learning-dependent BDNF levels in the rat medial prefrontal cortex: approach vs. withdrawal

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Abstract

This article presents a comparison of changes in molecular markers of systemogenesis related to behavioral motivation: approach versus avoidance, differing in their stress levels. We conducted an immunohistochemical study of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex of adult Long-Evans rats. Two groups were trained in a bar-pressing task: 1) to activate a food dispenser and obtain food (approach); 2) to terminate a shock and avoid pain (avoidance). The avoidance group showed significantly fewer BDNF-immunopositive cells in the prelimbic and infralimbic prefrontal cortex compared to the approach group. Furthermore, BDNF levels correlated with individual differences in anxiety and exploratory activity. We conclude that the medial prefrontal cortex is involved in both approach and avoidance behaviors, but to a significantly lesser extent in avoidance. The potential role of stress-induced neuroinflammation in these differences is discussed.

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About the authors

A. I. Bulava

Institute of Psychology of the Russian Academy of Sciences; Moscow Institute of Psychoanalysis

Author for correspondence.
Email: bulavaai@ipran.ru
Russian Federation, Moscow; Moscow

Yu. I. Alexandrov

Institute of Psychology of the Russian Academy of Sciences

Email: bulavaai@ipran.ru
Russian Federation, Moscow

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2. Fig. 1. Experimental timeline. Behavioral tests – the open-field and the novel object recognition modified tests. Instrumental learning – animals were trained food-acquisition (Group 1) or footshock-avoidance (Group 2) operant behavior. Pictures from the actual video recording during acquisition of operant behavior (food/footshock). IHC-Fr HRP – frozen brain sections immunoperoxidase staining of BDNF or NeuN.

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3. Fig. 2. (a) – schematic diagram of the rat brain (3.72 mm from Bregma), sagittal and frontal planes, region of interest are indicated; (б) – representative microphotographs of IHC-prepared tissue (HRP DAB) show NeuN and BDNF stained areas of medial prefrontal cortex (PrL), including negative controls (contr-, IHC excluding primary antibodies). Scale bar =200 µm; (в) – the relationship between learning and level of BDNF in rat neocortex. M ± SEM are shown. Appetitive – instrumental food-obtaining behavior (n = 13); Avoidance – instrumental footshock-avoidance behavior (n = 11); Int.contr – intact animals (n = 6). Kruskal–Wallis, PrL H(N30) = 19.6, p = 0.0001; IL H(N30) = 20.4, p = 0.00001. Mann–Whitney, *Z = 2.95, p = 0.003; **Z = 3.15, p = 0.001; (г) – graphs showing the correlations obtained between behavioral variables, such as freeze and vertical activity and the number BDNF-positive cells of the medial prefrontal cortex. Spearman, Freeze +PrL r = -0.56, p = 0.007; ++IL r = -0.53, p = 0.012. Vertical activity #PrL r = 0.78, p = 0.00002; ##IL r = 0.77, p = 0.00003.

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