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.

Neuroinflammation in the prefrontal-amygdala-hippocampus network is associated with maladaptive avoidance behaviour

“…In this test, the number of adaptive avoidance responses is scored along with the pattern of fear response exhibited to classify animals as presenting adaptive (AA) or maladaptive avoidance (MA) behaviour. Although this classification is commonly only established in the last two consecutive trials [ 3 , 4 , 18 ], behavioural differences between groups were observed since the first test and continued until the end of the experiment, suggesting that intrinsic differences between animals could determine a predisposition to develop maladaptive avoidance behaviour and exacerbated fear responses.…”

“…The test was performed as previously described [ 15 , 18 ]. Briefly, animals were tested 8 consecutive days (one 25-min session per day) in a two-way shuttle box placed inside a soundproof isolation cubicle (Insight Equipment, Brazil).…”

“…Controls animals were exposed to the two-way shuttle box for the same time/days as described above, but the footshock was turned off. The experimental animals that showed adaptive avoidance behaviour were included in the Adaptive Avoidance group (AA; >20 adaptive avoidance responses in two consecutive days), while the ones that showed a high fear response and maladaptive avoidance behaviour were included in the Maladaptive Avoidance group (MA; <20 adaptive avoidance responses) [ 15 , 18 ]. Freezing was defined as the absence of movement except that required for breathing, and it was assessed during the first 5 min of the test [ 15 , 19 ].…”

Unravelling the Role of Habenula Subnuclei on Avoidance Response: Focus on Activation and Neuroinflammation

“…The paradigm was performed as previously described [ 75 ]. In brief, animals were submitted to 25 min training sessions once a day for 8 consecutive days in a two-way shuttle box (Insight Equipment, Ribeirao Preto, Brazil).…”

“…Controls animals were exposed to the two-way shuttle box, but the footshock was turned off (i.e., without behavior contingency). Animals performing more than 20 avoidance responses in a session for 2 consecutive days were considered good performers, while animals that did not achieve this number were considered poor performers [ 7 , 75 , 76 ]. Freezing, defined as the absence of movement except that required for breathing [ 77 ], was assessed during the first 2 min of the tests [ 74 , 76 ].…”