Frustrative Nonreward: Behavior, Circuits, Neurochemistry, and Disorders.

The surprising omission or reduction of vital resources (food, fluid, social partners) can induce an aversive emotion known as frustrative nonreward (FNR), which can influence subsequent behavior and physiology. FNR is an integral mediator of irritability/aggression, motivation (substance use disorders, depression), anxiety/fear/threat, learning/conditioning, and social behavior. Despite substantial progress in the study of FNR during the twentieth century, research lagged in the later part of the century and into the early twenty-first century until the National Institute of Mental Health's Research Domain Criteria initiative included FNR and loss as components of the negative valence domain. This led to a renaissance of new research and paradigms relevant to basic and clinical science alike. The COVID-19 pandemic's extensive individual and social restrictions were correlated with increased drug and alcohol use, social conflict, irritability, and suicide, all potential consequences of FNR. This article highlights animal models related to these psychiatric disorders and symptoms and presents recent advances in identifying the brain regions and neurotransmitters implicated.

Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast.

The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala's involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.

Frustrative nonreward and the basal ganglia: Chemogenetic inhibition and excitation of the nucleus accumbens and globus pallidus externus during reward downshift.

Frustrative nonreward contributes to anxiety disorders and addiction, and is included in the Research Domain Criteria initiative as a relevant endophenotype. These experiments explored the role of the basal ganglia in consummatory reward downshift (cRD) using inhibitory and excitatory DREADDs (designer receptors exclusively activated by designer drugs) infused in either the nucleus accumbens (NAc) or one of its downstream targets, the globus pallidus externus (GPe). NAc inhibition did not disrupt consummatory suppression during a 32-to-2% (Experiment 1) or 8-to-2% sucrose downshift (Experiment 2). However, NAc excitation enhanced consummatory suppression during a 32-to-2% sucrose downshift (Experiment 1). GPe inhibition caused a trend toward increased consummatory suppression after a 32-to-2% sucrose downshift, whereas GPe excitation eliminated consummatory suppression after an 8-to-2% sucrose downshift (Experiment 3). Chemogenetic manipulations of NAc and GPe had no detectable effects on open field activity. The effects of DREADD activation via clozapine N-oxide (CNO) administration were compared to controls that carried the DREADDs, but received vehicle injections. There was no evidence that CNO or vehicle injections in virus vector control (VVC) animals affected cRD or OF activity after either CNO or vehicle injections. NAc and GPe excitation led to opposite results in the cRD task, providing evidence that the basal ganglia circuit has a function in frustrative nonreward in the absence of detectable motor effects.

Evidence of successive negative contrast in terrestrial toads (Rhinella arenarum): central or peripheral effect?

Prior research with terrestrial toads (Rhinella arenarum) in a water-reinforced instrumental situation indicated a direct relationship between acquisition rate and reward magnitude. However, a reward downshift produced a gradual adjustment of instrumental performance and a rapid adjustment of consummatory performance, rather than the abrupt and transient deterioration of behavior typical of a successive negative contrast effect. In Experiment 1, using a two-chamber box, a downshift from deionized water (which supports maximal rehydration) to 250-mM sodium chloride solution (which supports a lower rehydration), also yielded a gradual adjustment of instrumental behavior. In this experiment, animals received one trial per day and were allowed 300 s of access to the reward in the goal box. Experiment 2 used the same procedure, except that animals were allowed access to the solution in the goal box for 600 s. Under these conditions, reward downshift led to longer latencies (instrumental) and lower rehydration levels (consummatory) than those of unshifted controls, providing evidence for successive negative contrast. Unlike in similar experiments with mammals, the effect was not transient, but persisted relatively unmodified over twelve daily postshift trials. In this case, the possibility of adaptation of the peripheral mechanisms for water uptake is considered. The comparative relevance of these results is discussed in terms of habit formation versus expectancy-guided behavior in vertebrate learning.

Incentive disengagement and the adaptive significance of frustrative nonreward.

Mammals respond to an unexpected reward omission or reduction with a variety of behavioral and physiological responses consistent with an aversive emotion traditionally called frustrative nonreward. This review focuses on two aspects of frustrative nonreward, namely (1) the evidence for an aversive emotional state activated by the surprising omission or reduction of a rewarding outcome, and (2) the adaptive value of frustration. Frustrative nonreward has been mainly studied in terms of its mechanisms, across development in rats and across vertebrate species in comparative research. However, its adaptive function remains obscure. Following Domjan's approach to animal learning, this article explores a specific adaptive function hypothesis of frustrative nonreward called the incentive disengagement hypothesis. According to this hypothesis, the adaptive function of frustrative nonreward is to break an attachment to a site, situation, or stimulus that no longer yields appetitive resources (especially food and fluids) to promote the search for rewards in alternative locations. This function is of particular relevance given that mammals are especially vulnerable to reward loss due to their high metabolic rate and the energy demands of their relatively large brain.

Frustrative nonreward: Chemogenetic inactivation of the central amygdala abolishes the effect of reward downshift without affecting alcohol intake.

The role of the central amygdala (CeA) in the adjustment to a 32-to-2% sucrose downshift in the consummatory successive negative contrast (cSNC) task and in a free-choice 10% alcohol-water preference task (PT) was studied using chemogenetic inactivation. cSNC is a model of frustrative nonreward that enhances alcohol consumption. In Experiment 1, sessions 1-10 involved 5-min access to 32% sucrose and sessions 11-12 involved access to 2% sucrose. Vehicle or clozapine N-oxide (CNO; 1 or 3 mg/kg, ip), used later to activate the inhibitory designer receptor, was administered 30 min before sessions 11-12. There was no evidence that CNO affected consummatory behavior after the sucrose downshift. In Experiment 2, all animals received an infusion of the inhibitory designer receptor hM4D(Gi) into the CeA. After recovery, animals received access to either 32% or 2% sucrose on sessions 1-10, followed by 2% sucrose on sessions 11-12. Immediately after each 5-min sucrose session, animals received a 2-bottle, 1-h PT with 10% alcohol and water. CNO (3 mg/kg, ip) or vehicle was administered 30 min before sessions 11-12. CeA inactivation prior to sucrose downshift eliminated the cSNC effect, which was observed in vehicle controls. However, there was no evidence that CeA inactivation affected preference for 10% alcohol over water. These results support the hypothesis that CeA activity is critical for cSNC effect, an outcome consistent with the view that the amygdala plays a central role in frustrative nonreward.

Duration of extinction trials as a determinant of instrumental extinction in terrestrial toads (Rhinella arenarum).

Instrumental learning guides behavior toward resources. When such resources are no longer available, approach to previously reinforced locations is reduced, a process called extinction. The present experiments are concerned with factors affecting the extinction of acquired behaviors in toads. In previous experiments, total reward magnitude in acquisition and duration of extinction trials were confounded. The present experiments were designed to test the effects of these factors in factorial designs. Experiment 1 varied reward magnitude (900, 300, or 100 s of water access per trial) and amount of acquisition training (5 or 15 daily trials). With total amount of water access equated in acquisition, extinction with large rewards was faster (longer latencies in 900/5 than 300/15), but with total amount of training equated, extinction with small rewards was faster (longer latencies in 100/15 than 300/15). Experiment 2 varied reward magnitude (1200 or 120 s of water access per trial) while holding constant the number of acquisition trials (5 daily trials) and the duration of extinction trials (300 s). Extinction performance was lower with small, rather than large reward magnitude (longer latencies in 120/300 than in 1200/300). Thus, instrumental extinction depends upon the amount of time toads are exposed to the empty goal compartment during extinction trials.

Reward devaluation disrupts latent inhibition in fear conditioning.

Three experiments explored the link between reward shifts and latent inhibition (LI). Using consummatory procedures, rewards were either downshifted from 32% to 4% sucrose (Experiments 1-2), or upshifted from 4% to 32% sucrose (Experiment 3). In both cases, appropriate unshifted controls were also included. LI was implemented in terms of fear conditioning involving a single tone-shock pairing after extensive tone-only preexposure. Nonpreexposed controls were also included. Experiment 1 demonstrated a typical LI effect (i.e., disruption of fear conditioning after preexposure to the tone) in animals previously exposed only to 4% sucrose. However, the LI effect was eliminated by preexposure to a 32%-to-4% sucrose devaluation. Experiment 2 replicated this effect when the LI protocol was administered immediately after the reward devaluation event. However, LI was restored when preexposure was administered after a 60-min retention interval. Finally, Experiment 3 showed that a reward upshift did not affect LI. These results point to a significant role of negative emotion related to reward devaluation in the enhancement of stimulus processing despite extensive nonreinforced preexposure experience.

Behavioral plasticity in aneural organisms.

Few contemporary psychologists would probably object to the notion that cognitive processes contribute to behavioral plasticity (learning) and are intimately linked to brain function. However, growing evidence suggests that behavioral plasticity is present in organisms lacking neurons (i.e., aneural organisms). This possibility would imply that at least some cognitive processes might have preceded the evolution of nervous systems. Evidence of learning in aneural organisms is reviewed within a mechanistic framework emphasizing four levels of analysis: psychological, neurobiological, neurochemical, and cell-molecular. Learning phenomena ranging from habituation to conditioning have been reported in some aneural organisms, and some key examples are reviewed with attention to evidence of underlying mechanisms. Species comparisons are framed in terms of the central evolutionary concepts of homology and homoplasy. This evidence raises the question of what new behavioral capacities were supported by the evolution of neurons that were not possible before. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Runway extinction in terrestrial toads (Rhinella arenarum): Instrumental or Pavlovian?

Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300 s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600 s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300 s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.

Instrumental successive negative contrast in rats: Trial distribution, reward magnitude, and prefrontal cortex activation.

Successive negative contrast (SNC) has been used to study reward relativity, reward loss, and frustration for decades. In instrumental SNC (iSNC), the anticipatory performance of animals downshifted from a large reward to a small reward is compared to that of animals always reinforced with the small reward. iSNC involves a transient deterioration of anticipatory behavior in downshifted animals compared to unshifted controls. There is scattered information on the optimal parameters to produce this effect and even less information about its neural basis. Five experiments with rats trained in a runway to collect food pellets explored the effects of trial distribution (massed or spaced), amount of preshift training, reward disparity, and reward magnitude on the development of an iSNC effect. Start, run, and goal latencies were measured. Using spaced trials (one trial per day), evidence of the iSNC effect was observed with 24 preshift trials and a 32-to-4 pellet disparity. With massed trials (4 trials per session separated by 30-s intertrial intervals), evidence of iSNC was found with 12 preshift sessions (a total of 48 trials) and a 16-to-2 pellet disparity. The massed-training procedure was then used to assess neural activity in three prefrontal cortex areas using c-Fos expression in animals perfused after the first downshift session. There was evidence of increased activation in the anterior cingulate cortex and a trend toward increased activation in the infralimbic and prelimbic cortices. These procedures open a venue for studying the neural basis of the instrumental behavior of animals that experience reward loss.

Open field activity is linked to, but is not affected by, the rate of recovery from reward downshift in female Wistar rats.

Frustration is an aversive emotion triggered by unexpected reward downshifts. Using the consummatory successive negative contrast (cSNC) task, a 32-to-2% sucrose downshift was shown to initially suppress consummatory behavior. Such suppression was followed by behavioral recovery over subsequent sessions. Individual differences often emerge in the rate of recovery after the initial consummatory suppression. These experiments were designed to determine whether a stable trait of sensation/novelty seeking (SNS) is related to such individual differences in recovery from reward downshift. In Experiment 1, open field (OF) activity in the central area served as a measure of SNS. A week later, animals received training in the cSNC task involving ten 5-min sessions of access to 32% sucrose followed by four sessions of access to 2% sucrose. Higher OF activity predicted greater consummatory suppression after downshift, but a steeper recovery rate across downshifted sessions. Controls not exposed to the OF showed cSNC, but downshifted animals performed at equivalent levels whether they had OF exposure or not. In Experiment 2, after a 32-to-2% sucrose downshift, fast vs. slow recovery animals displayed similar levels of central activity in the OF. In Experiment 3, animals exhibited similar levels of central activity whether after a 32-to-2% or an 8-to-2% sucrose downshift. In both experiments, activity levels were similar whether immediately after session 12 (onset of recovery) or after session 15 (fully recovered). These results suggest that individual variations in recovery from reward downshift are correlated with levels of SNS as a stable trait.

Behavioral and neural correlates of licking for 66% alcohol in Wistar rats: Caloric balance or sensation/novelty seeking?

Whereas rodents generally reject high alcohol concentrations, access to 66% alcohol can reinforce operant licking in a progressive ratio situation. Three experiments were conducted to identify a potential mechanism underlying this effect. In Experiment 1, food-restricted male and female Wistar rats received access to either 66% alcohol or water in their home cage for one hour over four sessions. Consumption of alcohol and water was similar, showing that rats neither preferred nor rejected 66% alcohol. Peripheral (but not central) activity in an open field (OF) was higher after access to 66% alcohol than water, a result inconsistent with motor impairment. Blood alcohol concentration was higher after 66% alcohol than water and was positively correlated with fluid displacement and peripheral distance in the OF. c-Fos immunoreactivity after exposure to 66% alcohol vs. water showed increased activation in the nucleus accumbens shell, anterior cingulate cortex, and insular cortex. In Experiment 2, whether access to food was restricted (to an 81-84% of the ad libitum weight) or free (ad libitum), female Wistar rats licked at similar frequency from a sipper tube delivering 66% alcohol. This result is inconsistent with an account based on the caloric content of 66% alcohol. In Experiment 3, food-restricted male and female Wistar rats exhibited a positive correlation between activity in the central area of an OF (an index of sensation/novelty seeking) and licking for 66% alcohol. These results are consistent with the hypothesis that the reinforcing value of 66% alcohol is related to sensation/novelty seeking.

Peripheral bacterial endotoxin administration triggers both memory consolidation and reconsolidation deficits in mice.

Peripherally administered inflammatory stimuli, such as lipopolysaccharide (LPS), induce the synthesis and release of proinflammatory cytokines and chemokines in the periphery and the central nervous system, and trigger a variety of neurobiological responses. Indeed, prior reports indicate that peripheral LPS administration in rats disrupts contextual fear memory consolidation processes, potentially due to elevated cytokine expression. We used a similar, but partially olfaction-based, contextual fear conditioning paradigm to examine the effects of LPS on memory consolidation and reconsolidation in mice. Additionally, interleukin-1ß (IL-1ß), brain-derived neurotrophic factor (BDNF), and zinc finger (Zif)-268 mRNA expression in the hippocampus and the cortex, along with peripheral cytokines and chemokines, were assessed. As hypothesized, LPS administered immediately or 2 h, but not 12 h, post-training impaired memory consolidation processes that support the storage of the conditioned contextual fear memory. Additionally, as hypothesized, LPS administered immediately following the fear memory trace reactivation session impaired memory reconsolidation processes. Four hours post-injection, both central cytokine and peripheral cytokine and chemokine levels were heightened in LPS-treated animals, with a simultaneous decrease in BDNF, but not Zif-268, mRNA. Collectively, these data reinforce prior work showing LPS- and cytokine-related effects on memory consolidation, and extend this work to memory reconsolidation.

Frustrative nonreward and emotional self-medication:Factors modulating alcohol consumption following reward downshift in rats.

Life experience involving unexpected incentive loss (e.g., loss of job or a significant other) may result in negative emotional reactions (frustration) and promote alcohol drinking. Similarly, animals exposed to a frustrative 32-to-4% sucrose downshift increase their preference for alcohol (2%) vs. water. This result was interpreted as reflecting emotional self-medication-the consumption of substances that reduce negative emotions. We conducted three experiments examining parametric manipulations of the animal model: (1) effects of a severe reward downshift (32-to-4% sucrose) on consumption of various alcohol concentrations (Experiment 1); (2) effects of different magnitudes of reward downshifts on consumption of 32% alcohol (Experiment 2); and (3) effects of partial reinforcement (an intervention that increases resistance to frustration) on 2% alcohol intake induced by a 32-to-4% sucrose downshift (Experiment 3). The results show that (1) a 32-to-4% sucrose downshift leads to an increase in alcohol intake over a wide range of alcohol concentrations; (2) the greater the reward downshift, the higher the relative increase in alcohol consumption; and (3) a treatment that increases resistance to frustration (partial reinforcement) also attenuates alcohol consumption after a sucrose downshift. These data are discussed in relation to the role of frustrative nonreward in alcohol consumption.

Psychological pain and opioid receptors: Reward downshift is disrupted when tested in a context signaling morphine.

A sucrose downshift causes a temporary suppression of consumption accompanied by psychological pain, a negative emotion triggered by reward loss. When administered systemically before downshift sessions, opioid agonists reduce and opioid antagonists enhance such behavioral suppression. However, little is known about the effects of signals of opioid drugs on behavior during a reward downshift episode. Research showed that morphine administration can induce a direct effect (e.g., hypoalgesia) followed by a compensatory effect (e.g., hyperalgesia). Therefore, a signal for morphine could elicit either a direct or a compensatory effect. Male Wistar rats were exposed to ten 5-min sessions of access to 32% sucrose in context A, followed by three sessions of access to 4% sucrose in context B. In parallel, animals received pairings between context B and morphine (5 mg/kg, sc) occurring each day immediately after sucrose sessions (contexts were counterbalanced). Control conditions included a saline control (no morphine injected), an unpaired control (morphine injected after exposure to B) tested in A (Experiment 1), and an unpaired control tested in B (Experiment 2). In both experiments, behavioral suppression induced by the 32-to-4% sucrose downshift was attenuated when the downshift occurred in a context previously paired with morphine. These data are consistent with the hypothesis that reward downshift is accompanied by an emotion of negative valence that can be counteracted by the conditioned release of endogenous opioids triggered by signals of morphine, much like it is attenuated by systemic morphine administration. Alternative hypotheses are also discussed.

Frustrative nonreward and cannabinoid receptors: Chronic (but not acute) WIN 55,212-2 treatment increased resistance to change in two reward downshift tasks.

Assessing the role of cannabinoid (CB) receptors in behavior is relevant given the trend toward the legalization of medicinal and recreational marijuana. The present research aims at bridging a gap in our understanding of CB-receptor function in animal models of frustrative nonreward. These experiments were designed to (1) determine the effects of chronic administration of the nonselective CB1-receptor agonist WIN 55,212-2 (WIN) on reward downshift in rats and (2) determine whether the effects of chronic WIN were reducible to acute effects. In Experiment 1, chronic WIN (7 daily injections, 10 mg/kg, ip) accelerated the recovery of consummatory behavior after a 32-to-4% sucrose downshift relative to vehicle controls. In addition, chronic WIN eliminated the preference for an unshifted lever when the other lever was subject to a 12-to-2 pellet downshift in free-choice trials, but only in animals with previous experience with a sucrose downshift. In Experiment 2, acute WIN (1 mg/kg, ip) reduced consummatory behavior, but did not affect recovery from a 32-to-4% sucrose downshift. The antagonist SR 141716A (3 mg/kg, ip) also failed to interfere with recovery after the sucrose downshift. In Experiment 3, acute WIN administration (1 mg/kg, ip) did not affect free-choice behavior after a pellet downshift, although it reduced lever pressing and increased magazine entries relative to vehicle controls. The effects of chronic WIN on frustrative nonreward were not reducible to acute effects of the drug. Chronic WIN treatment in rats, like chronic marijuana use in humans, seems to increase resistance to the effects of frustrative nonreward.

Recovery profiles from reward downshift are correlated with operant licking maintained by alcohol, but not with genetic variation in the mu opioid receptor.

After ten 5-min sessions of access to 32% sucrose, a reward downshift (RD) to 2% sucrose induces a transient rejection of the reward. Animals were segregated according to the speed of recovery from RD into Fast-recovery and Slow-recovery subgroups. Animals were subsequently trained in an operant licking (OL) task in which licking at an empty tube provided 10 s of access to a second tube containing 66% alcohol. Licking on the first tube was subjected to a progressive ratio (PR) schedule with a step of 4 licks. Fast-recovery animals (both males and females) licked to a higher ratio than Slow-recovery animals. Animals were also exposed to a well-lit open field (OF) for 20 min. Fast- and Slow-recovery males and females exhibited equal levels of activity in the OF. Tissue samples from tails were assessed for two well-known allelic variations of the human opioid receptor gene, OPRM1, known to affect mu opioid sensitivity: The C17T and A118G single nucleotide polymorphisms. There was no evidence of a relationship between genotype and behavior, suggesting that these genetic mechanisms in humans do not account for the individual differences in recovery from RD and OL for alcohol in rats.

Reinforcing properties of alcohol in rats: Progressive ratio licking performance reinforced with 66% alcohol.

Rodents are generally reluctant to consume high concentrations of alcohol. However, few experiments have reported the behavior of rats when they are given access to high alcohol concentrations. Four experiments with food-deprived Wistar rats were designed to determine whether 66% alcohol could be used as a positive reinforcer for operant responses. In Experiment 1, animals learned to lick an empty sipper to gain access to 66% alcohol in a second tube; licking extinguished after it if provided a only access to water (operant licking task, OL). Experiment 2 used the OL task combined with a progressive ratio (PR) schedule in a within-subject design with the order of alcohol concentrations counterbalanced across subjects. The breakpoint (the last completed ratio in the PR schedule) was higher for 10% and 66% alcohol concentrations than for water. In Experiment 3, animals trained in the same PR task gained access to water, 10%, or 66% alcohol in a between-subject design. Breakpoints were higher for 66% alcohol than for water, but not for 10% alcohol relative to water. Experiment 4 tested the effects of the orexin-1 receptor antagonist SB-334,867 on licking reinforced with access to 66% alcohol in the PR task. The antagonist reduced the breakpoint at 1- and 5-mg/kg doses, but not at 10 mg/kg. These results suggest that 66% alcohol can be used to reinforce operant behavior. Although the effects were modest, they were reliable. The estimated amount of alcohol consumed in the OL task suggests that these reinforcing effects were not dependent on the pharmacological effects of 66% alcohol, but could perhaps reflect a sensation-seeking effect.

Effects of alcohol consumption induced by reward loss on behavior in the hole-board test.

Rats exposed to reward downshift (from 32 to 4% sucrose) increase 2% alcohol intake in a 2-h, free-choice preference test which also offered water. This effect was accompanied by augmented general activity in the elevated plus maze (Donaire et al., 2018, Behav Proc, 150, 59-65). In the present study we analyzed the effect of alcohol consumption induced by reward downshift on anxiety behaviors registered in the hole-board (HB) test. Sixteen food-deprived female Wistar rats received 32% sucrose for ten 5-min daily sessions and were then downshifted to 4% sucrose for two 5-min daily sessions (postshift). Sessions also involved testing animals in a 2-h, 2-bottle preference task with 2% alcohol vs. water (Group A), or water vs. water (Group W). On postshift sessions, animals were exposed to a 6-min HB test after the preference task. Reward devaluation significantly reduced sucrose intake in Groups A and W, and increased alcohol consumption in Group A, but had no effect on water consumption in Group W. Increased alcohol consumption was followed by higher head-dipping frequency in the HB test compared with Group W. The results are discussed in terms of the impact of reward loss on anxiety behaviors in the HB test and the anxiolytic effects of alcohol in situations involving negative affect.