Incentive Relativity: Gene-Environment Interactions

Abstract

Reward loss experiences are among the main sources of emotional stress that humans face throughout their lives. In the animal laboratory, it has been repeatedly shown that the unexpected omission or devaluation of a reinforcer triggers a physiological, cognitive, and behavioral state called frustration. This state involves emotional mechanisms that resemble those unleashed by the presentation of other aversive stimuli, inducing similar stress responses through the activation of brain circuits involved in fear and anxiety. Although this hypothesis has been supported by behavioral, pharmacological, hormonal, and neurobiological evidence, only a few studies have focused on the neurogenetic basis of frustration in animals. This review focuses on the gene-environment interactions that determine the emotional response under conditions of reward loss. Behavioral and genetic correlates of frustration are reviewed in two strains of animals selected on the basis of extreme differences in active avoidance learning: inbred Roman High- (RHA-I) and Roman Low-Avoidance (RLA-I) rats. The review shows the usefulness of Roman strains for neurogenetic research and sets out unsolved questions regarding gene-environment interactions underlying behavior induced by incentive loss.

Neurobehavioral and neurodevelopmental profiles of a heuristic genetic model of differential schizophrenia- and addiction-relevant features: The RHA vs. RLA rats

“…(ii)-First quantitative genetic study on multiple anxiety-related traits, with > 800 F2 rats of both sexes (hybrids from the inbred RHA and RLA strains), revealing for the first time in rats the existence of pleiotropic QTL ("quantitative trait loci") influencing several conditioned and unconditioned anxiety-and fear-related traits. Aguilar et al, 2002bAguilar et al, , 2003Escorihuela et al, 1999;Fernandez-Teruel et al, 2002b (see also Johannesson et al, 2009) Supplementary Table 1 (continued) Mont et al, 2018 (iii)-Convincing evidence that, besides being anxious and passive coping animals, RLA rats display enhanced frustration responses to incentive loss in different paradigms, and might constitute a unique tool for research on the neurobiology of frustration Cuenya et al, 2012Cuenya et al, , 2015Gomez et al, 2008Gomez et al, , 2009aManzo et al, 2014aManzo et al, , 2015Moron et al, 2010;Papini et al, 2015;Rosas et al, 2007;Sabariego et al, 2011Sabariego et al, , 2013Torres and Sabariego 2014;Torres et al, 2005Torres et al, , 2007 (iv)-RHA (but not RLA) rats show a stop codon mutation at cysteine 407 in Grm2 (cys407*; mGlu2 receptor), which allows the RHA strain to represent a naturally-occurring "knock out" of mGlu2 receptors Wood et al, 2017(see also Fomsgaard et al, 2018Klein et al, 2014) (v)-As compared to RLA rats, RHA rats exhibit impulsivity in several tasks, impaired attentional/cognitive profiles and alterations of social behavior, decreased volume and/or activity of the medial prefrontal cortex (PFC), hippocampus and amygdala, as well as a number of alterations of neurodevelopment-related pre-/postsynaptic markers and in the pyramidal spine density in the PFC, all of which indicate the presence of an immature PFC and a schizophrenia-like phenotypic profile in RHA rats Merchan et al, 2019;Moreno et al, 2010;Del Río et al, 2014;Río-Álamos et al, 2017aRío-Álamos et al, , 2019…”

Comparative learning and evolution.

“…This research has revealed some of the key determinants of the SNC effect, including its dependence on the degree of reward disparity and type: ratio invariance regulates the detection of a reward downshift, incentive contrast phenomena require limbic and prefrontal cortex processing, GABAergic and opioidergic pathways are critically and specifically involved in regulating these effects, and these effects require the expression of specific genes in neural tissue (Flaherty, 1996;M. R. Papini, 2009;Torres & Sabariego, 2014). The research on learning phenomena involving reward downshifts reviewed later in this chapter provides a window into the type of knowledge and problems derived from comparative research on learning.…”

“…Many studies of selective breeding for behavioral divergence show a rapid response, indicating the presence of hereditary factors through which a differential set of alleles can bias specific behavioral traits. Several studies have explored the genetic basis of sensitivity to reward loss (see Chapter 16, this volume) by using strains of rats selectively bred for divergent emotional reactivity, fearfulness, or anxiety, as well as with respect to their divergence in the size of the cSNC effect (M. R. Papini et al, 2015;Torres & Sabariego, 2014). Flaherty, Krauss, Rowan, and Grigson (1994) selectively bred Sprague-Dawley rats showing large versus small cSNC effects over seven generations.…”

“…The most extensive effort to explore this topic has been conducted in the inbred Roman highavoidance (RHA) and Roman low-avoidance (RLA) strains of rats, selectively bred for extreme divergence in a two-way avoidance learning task. Originally selected from Wistar rats, RHA and RLA rats differ in anxiety or emotional reactivity (low in RHA, high in RLA rats), as well as with respect to novelty seeking, impulsivity, drug consumption and abuse, psychotic-like symptoms, offensive aggression, sensitivity to antidepressant, and sexual behavior (M. R. Papini et al, 2015;Torres & Sabariego, 2014).…”