A Window on the Study of Aversive Instrumental Learning: Strains, Performance, Neuroendocrine, and Immunologic Systems

Abstract

The avoidance response is present in pathological anxiety and interferes with normal daily functions. The aim of this article is to shed light on performance markers of active avoidance (AA) using two different rat strains, Sprague-Dawley (SD) and Wistar. Specifically, good and poor performers were evaluated regarding anxiety traits exhibited in the elevated plus maze (EPM) and corticosterone levels and motor activity in the open field test. In addition, the plasma levels of Interleukin-6 (IL-6), Interleukin-1Beta (IL-1beta), Nerve Growth Factor Beta (NGF-beta), Tumor Necrosis Factor-Alpha (TNF-alpha) and cytokine-induced neutrophil chemoattractant 1 (CINC-1) were compared in the good and poor performers to better understand the role of the immunologic system in aversive learning. Behavioral criteria were employed to identify subpopulations of SD and Wistar rats based on their behavioral scores during a two-way AA test. The animals were tested for anxiety-like behavior in the EPM and motor activity in the open-field test. Plasma corticosterone levels were measured at the end of the avoidance test. Cytokine levels of IL-6, IL-1beta, NGF-beta, TNF-alpha, and CINC-1 were measured in the plasma of the Wistar rats. Sixty-six percent of the Wistar rats and 35% of the SD rats exhibited a poor performance. This feature was associated with a decrease in anxiety-like behavior in the EPM. The poor and good performers exhibited lower levels of corticosterone compared with the control animals, which suggests that training alters corticosterone levels, thereby leading to hypocortisolism, independent of the performance. The CINC-1 levels were increased in the poor performers, which reinforces the role of immunologic system activation in learning deficits. Our study provides a better understanding of the complex interactions that underlie neuroimmune consequences and their implications for performance.

Keywords: anxiety; aversive instrumental learning; avoidance; corticosterone; elevated plus-maze; immunologic system.

Figure 1

Number of active avoidance responses in good and poor performers across training sessions with Wistar (A) and Sprague Dawley (B) rats. Data represent means ± SEMs. ^*P < 0.05 vs. poor performer, ^#P < 0.05 vs. good and poor performers. SD Good, Sprague Dawley good performers (n = 14); SD Poor, Sprague Dawley poor performers (n = 10); SD Control, Sprague Dawley control rats (n = 5); Wistar Good, Wistar good performers (n = 8); Wistar Poor, Wistar poor performers (n = 15); Wistar Control, Wistar control rats (n = 5).

Figure 2

Entries (A) and time spent (B) in the open arms by good and poor performers in the different strains of Wistar and Sprague Dawley rats. Bars represent the means, and the vertical lines indicate the SEMs. ^&P < 0.05 vs. all other groups. SD Good, Sprague Dawley good performers (n = 14); SD Poor, Sprague Dawley poor performers (n = 10); Wistar Good, Wistar good performers (n = 8); Wistar Poor, Wistar poor performers (n = 15).

Figure 3

Total distance traveled in the open field by good and poor performers in different strains of Wistar and Sprague Dawley rats. Bars represent the means, and the vertical lines indicate the SEMs. SD Good, Sprague Dawley good performers (n = 14); SD Poor, Sprague Dawley poor performers (n = 10); Wistar Good, Wistar good performers (n = 8); Wistar Poor, Wistar poor performers (n = 15).

Figure 4

Effects of AA training on corticosterone levels (pg/dL) in control, good and poor avoiders of two different strains: SD Sprague Dawley and Wistar. Bars represent the means, and the vertical lines indicate the SEMs. ^#P < 0.05 vs. good and poor performers. ^&P < 0.05 vs. all other groups. SD Good, Sprague Dawley good performers (n = 14); SD Poor, Sprague Dawley poor performers (n = 10); SD Control, Sprague Dawley control rats (n = 5); Wistar Good, Wistar good performers (n = 8); Wistar Poor, Wistar poor performers (n = 15); Wistar Control, Wistar control rats (n = 5).

Figure 5

Plasma concentration of cytokine-induced neutrophil chemoattractant 1 (CINC-1) in the Wistar lineage assessed by enzyme-linked immunosorbent assay. The data are represented in pg/mL; the bars represent the means, and the vertical lines indicate the SEMs. ^&P < 0.05 vs. Control and Good performers. Wistar Good, Wistar good performers (n = 8); Wistar Poor, Wistar poor performers (n = 15); Wistar Control, Wistar control rats (n = 5).