Emotional reactivity to incentive downshift as a correlated response to selection of high and low alcohol preferring mice and an influencing factor on ethanol intake

Abstract

Losing a job or significant other are examples of incentive loss that result in negative emotional reactions. The occurrence of negative life events is associated with increased drinking (Keyes et al., 2011). Further, certain genotypes are more likely drink alcohol in response to stressful negative life events (Blomeyer et al., 2008; Covault et al., 2007). Shared genetic factors may contribute to alcohol drinking and emotional reactivity, but this relationship is not currently well understood. We used an incentive downshift paradigm to address whether emotional reactivity is elevated in mice predisposed to drink alcohol. We also investigated if ethanol drinking is influenced in High Alcohol Preferring mice that had been exposed to an incentive downshift. Incentive downshift procedures have been widely utilized to model emotional reactivity, and involve shifting a high reward group to a low reward and comparing the shifted group to a consistently rewarded control group. Here, we show that replicate lines of selectively bred High Alcohol Preferring mice exhibited larger successive negative contrast effects than their corresponding replicate Low Alcohol Preferring lines, providing strong evidence for a genetic association between alcohol drinking and susceptibility to the emotional effects of negative contrast. These mice can be used to study the shared neurological and genetic underpinnings of emotional reactivity and alcohol preference. Unexpectedly, an incentive downshift suppressed ethanol drinking immediately following an incentive downshift. This could be due to a specific effect of negative contrast on ethanol consumption, or a suppressive effect on consummatory behavior in general. These data suggest that alcohol intake either doesn’t provide the anticipated negative reinforcement, or that a single test was insufficient for animals to learn to drink following incentive downshift. However, that high drinking and emotional intensity following incentive downshift provide initial evidence that this type of emotional reactivity may be a predisposing factor in alcoholism.

High Alcohol–Preferring Mice Show Reaction to Loss of Ethanol Reward Following Repeated Binge Drinking

“…It is not clear whether the difference between HAP mice and B6 mice is specific to cSNC or whether this may indicate important differences between these populations in sensitivity to EtOH's rewarding effects. In other strain comparisons of cSNC, previous research has demonstrated that in a sucrose downshift paradigm, HAP replicates display greater cSNC than LAPs (Matson and Grahame, 2015). LAP mice will not drink EtOH, and therefore, we cannot assess whether EtOH cSNC would be found in them.…”

“…The cognitive state induced by this downshift has classically been described as frustration (Amsel, 1962;Amsel, 1992). The relationship between EtOH and cSNC has primarily been studied within the context of assessing the ability of EtOH to relieve the frustrative effects associated with a sucrose downshift (Becker and Flaherty, 1982;Manzo et al, 2015;Manzo et al, 2014a;Matson and Grahame, 2015). Interestingly, cSNC is greater in mice genetically predisposed to excessive alcohol consumption than their corresponding low alcoholpreferring (LAP) lines when using a shift from 32% sucrose to 4% sucrose (Matson and Grahame, 2015).…”

“…The relationship between EtOH and cSNC has primarily been studied within the context of assessing the ability of EtOH to relieve the frustrative effects associated with a sucrose downshift (Becker and Flaherty, 1982;Manzo et al, 2015;Manzo et al, 2014a;Matson and Grahame, 2015). Interestingly, cSNC is greater in mice genetically predisposed to excessive alcohol consumption than their corresponding low alcoholpreferring (LAP) lines when using a shift from 32% sucrose to 4% sucrose (Matson and Grahame, 2015). Both frontloading and cSNC have also been observed in HAP1 mice following an unexpected switch from an EtOH solution to a water solution (Linsenbardt and Boehm, 2015).…”

The effects of ethanol on diverse components of choice in the rat: reward discrimination, preference and relative valuation

“…This ‘protective’ effect of alcohol against frustration experienced during negative contrast fits the tension‐reduction hypothesis in that alcohol may reduce anxiety caused by reward downshift. As a negative experience, contrast can impact alcohol intake (Matson & Grahame, ) and vice versa (Cox, ). Our work provides a novel view of contrast over weekly experiences with an identical outcome paired with different alternatives.…”

“…Previous work with rats has investigated alcohol's effect on different components of choice that include reward discrimination between quantitative (Martinetti et al ., ) and qualitative (Samson et al ., ) shifts in natural reward (i.e., sucrose) as well as preference for diverse outcomes including alcohol (Tomie et al ., ; Morales et al ., ). Separate work with mice has investigated alcohol's effect on relative valuation of sucrose outcomes using a standard incentive contrast paradigm (Matson & Grahame, ). These traditional approaches focus on a specific behavioral component which can be effective at assessing reward processing and choice.…”