Levonorgestrel maintains goal-directed behavior in habit-trained intact female rats.

Hormonal contraceptives are utilized by millions of women worldwide. However, it remains unclear if these powerful endocrine modulators may alter cognitive function. Habit formation involves the progression of instrumental learning as it goes from being a conscious goal-directed process to a cue-driven automatic habitual motor response. Dysregulated goal and/or habit is implicated in numerous psychopathologies, underscoring the relevance of examining the effect of hormonal contraceptives on goal-directed and habitual behavior. This study examined the effect of levonorgestrel (LNG), a widely used progestin-type contraceptive, on the development of habit in intact female rats. Rats were implanted with subcutaneous capsules that slowly released LNG over the course of the experiment or cholesterol-filled capsules. All female rats underwent operant training followed by reward devaluation to test for habit. One group of females was trained at a level that is sub-threshold to habit, while another group of females was trained to a level well over the habit threshold observed in intact females. The results reveal that all sub-threshold trained rats remained goal-directed irrespective of LGN treatment, suggesting LNG is not advancing habit formation in female rats at this level of reinforcement. However, in rats that were overtrained well above the threshold, cholesterol females showed habitual behavior, thus replicating a portion of our original studies. In contrast, LNG-treated habit-trained rats remained goal-directed, indicating that LNG impedes the development and/or expression of habit following this level of supra-threshold to habit training. Thus, LNG may offset habit formation by sustaining attentional or motivational processes during learning in intact female rats. These results may be clinically relevant to women using this type of hormonal contraceptive as well as in other progestin-based hormone therapies.

Longitudinal and experimental investigations of implicit happiness and explicit fear of happiness.

ABSTRACTSome individuals devalue positivity previously associated with negativity (Winer & Salem, 2016). Positive emotions (e.g. happiness) may be seen as threatening and result in active avoidance of future situations involving positivity. Although some self-report measures can capture emotions of happiness-averse individuals, they are not always capable of capturing automatic processing. Thus, we examined the association between implicitly-assessed happiness and explicit (i.e. self-reported) fear of happiness in three studies. In Study 1, participants completed the Fear of Happiness Scale (FHS) and an implicit measure of emotions at four-time points over approximately one year. The implicit measure required participants to choose which emotion (i.e. anger, fear, happiness, sadness, or none) best corresponded to 20 individual Chinese characters. In Studies 2 and 3, we utilized an experimental design, implementing a mood induction to emphasise the relationship between explicit fear of happiness and implicitly-assessed happiness. Participants completed the FHS and chose which emotion they believed the artist tried to convey in 20 abstract images. Results indicated that greater self-reported fear of happiness was related to reduced implicit happiness. Findings from these studies provide compound evidence that individuals who hold negative views of positivity may process implicit happiness in a devaluative manner.

A network analytic investigation of avoidance, dampening, and devaluation of positivity.

BACKGROUND AND OBJECTIVES: Reward Devaluation Theory suggests that devaluation of positivity may be integral in understanding depression (Winer & Salem, 2016). Specifically, the anticipatory (e.g., fear of happiness) and responsive (e.g., dampening) behaviors related to the processing of positivity may play a role in the development and maintenance of depression. METHODS: The goal of this study was to examine the potential overlap between measures that operationalize positivity avoidance, two Fear of Happiness Scales (Gilbert et al., 2012; Joshanloo, 2013), as well as positivity dampening, measured via the dampening subscale of the Responses to Positive Affect Questionnaire (Feldman et al., 2008). Network and community analyses were employed to examine the extent to which the items of these measures clustered into their parent measures and investigate the dynamic interactions between items. RESULTS: The results of the community analysis revealed that the three self-report measures overall clustered into their parent measures, except for the Gilbert et al. (2012) Fear of Happiness Scale, which clustered into two separate communities. The most influential nodes represented the concept that good feelings are often followed by negative outcomes. Additionally, nodes related to the theme of fear of letting oneself become happy emerged as the strongest bridge nodes. LIMITATIONS: One limitation of this study is the use of a cross-sectional design; thus, causality cannot be inferred, but the results can guide future longitudinal network designs. CONCLUSIONS: These findings demonstrate how anticipatory avoidance and responsive dampening may influence depression, thus providing evidence for unique targets for treatment.

Individuals fearing positivity do not perceive positive affect treatments as strong fits: A novel experimental finding and replication.

BACKGROUND AND OBJECTIVES: Positive affect treatments, which hold great promise to connect with those who are otherwise resistant to depression treatments, attempt to upregulate positive emotions. These treatments have potential advantages over standard therapies because they target cross-diagnostic core symptoms (e.g., anhedonia) that may respond better to interventions aimed at increased positivity. However, the extent to which these treatments are a perceived fit by individuals for whom they were developed (i.e., individuals who are afraid of, avoid, or experience less positivity) is unclear. METHODS: We conducted two independent studies utilizing a cross-sectional, experimental design to examine perceived treatment fit. Participants (Study 1: N = 416; Study 2: N = 321) read counterbalanced treatment descriptions of (1) positive affect treatment and (2) psychodynamic psychotherapy and answered questions regarding perceived treatment fit, effectiveness, and preference of the two treatments. RESULTS: Our findings suggest that individuals fearful of happiness perceived a prospective depression treatment specifically targeting positivity as a poorer fit, demonstrating an opposite pattern to the overall samples' treatment preference in both studies. Thus, as predicted by Reward Devaluation Theory, those fearing positivity exhibited avoidance behaviors for treatments that are to an extent designed, and might otherwise be most effective, for them. LIMITATIONS: The current study utilized a college student sample. CONCLUSION: These empirical findings may ultimately inform psychoeducation of why positive affect treatments, which are in direct contrast with clients' preferences, may be the very treatments they need the most.

Greater avoidance of a saccharin cue paired with passive delivery of heroin is associated with a select increase in expression of CRFR2 and CRFbp in the hippocampus in rats.

As a drug of abuse tightens its hold on addicted individuals, aspects of life that once brought pleasure lose their appeal while attention and motivation are turned toward acquiring drug. In a rodent model of self-administration and reward devaluation, we previously showed that animals that suppress intake of a drug-paired saccharin cue show greater addiction-like behaviors, as well as increased gene-expression of elements of the corticotropin releasing factor (CRF) pathway in the prefrontal cortex (mPFC), hippocampus (Hipp), and ventral tegmental area (VTA). In the present study, we explored whether the observed differences in components of the CRF signaling pathway were a function of self-administration or devaluation of the cue. Moreover, as an increasing body of work illustrates, functional and molecular hemispheric differences in reward pathway components, we examined whether these CRF pathway components exhibited hemispheric differences in response to heroin administration. Over a period of 7 trials, 30 male rats received brief access to saccharin followed by passive (IP) injection of heroin (n = 20) or saline (n = 10). Saccharin intakes between large saccharin suppressors (LS; 12 animals) and small suppressors (SS; 8 animals) were statistically different after trial 1 and separated further with ensuing trials. We then assessed gene expression for components of the CRF pathway in the mPFC, Hipp, VTA, Amygdala, and nucleus accumbens (NAc). Within the Hipp, LS showed greater expression of CRF binding protein (CRFbp). No differences were observed in the mPFC, VTA, NAc or Amygdala. Several hemisphere differences in CRF signaling pathway genes were detected. These findings indicate that avoidance of the experimenter delivered heroin-paired saccharin cue, do not recapitulate findings observed for avoidance of the iv self-administered heroin-paired saccharin cue, at least in terms of the expression of genes within the CRF pathway, and provide further evidence that consideration should be given to hemisphere differences when exploring molecular phenomena.

Compulsive Eating in a Rat Model of Binge Eating Disorder Under Conditioned Fear and Exploration of Neural Mechanisms With c-fos mRNA Expression.

Compulsive eating is the most obstinate feature of binge eating disorder. In this study, we observed the compulsive eating in our stress-induced binge-like eating rat model using a conflicting test, where sucrose and an aversively conditioned stimulus were presented at the same time. In this conflicting situation, the binge-like eating prone rats (BEPs), compared to the binge-like eating resistant rats (BERs), showed persistent high sucrose intake and inhibited fear response, respectively, indicating a deficit in palatability devaluation and stronger anxiolytic response to sucrose in the BEPs. We further analyzed the neuronal activation with c-fos mRNA in situ hybridization. Surprisingly, the sucrose access under conditioned fear did not inhibit the activity of amygdala; instead, it activated the central amygdala. In the BEPs, sucrose reduced the response of the paraventricular hypothalamic nucleus (PVN), while enhancing activities in the lateral hypothalamic area (LHA) to the CS. The resistance to devaluating the palatable food in the BEPs could be a result of persistent Acb response to sucrose intake and attenuated recruitment of the medial prefrontal cortex (mPFC). We interpret this finding as that the reward system of the BEPs overcame the homeostasis system and the stress-responding system.

Examining rumination, devaluation of positivity, and depressive symptoms via community-based network analysis.

OBJECTIVE: Components of rumination, including brooding and reflection, as well as devaluating prospective positivity, may help maintain depressive symptoms. We examined these components together for the first time using network analysis. METHODS: We examined the robustness of rumination communities of closely related items in one network and then examined the interrelationships between rumination communities, devaluation of positivity, and depression, in a second network. RESULTS: Three rumination communities emerged, replicating findings of Bernstein et al. (2019). Within a dense network, nodes representing brooding, reflective pondering, and difficulty trusting positive feelings were most influential. In addition, the node representing the depressive symptom negative self-views shared strong edges with nodes representing devaluation of positivity and brooding. CONCLUSION: Brooding, reflective pondering, and elements of devaluing positivity are influential to depressive symptoms and may be important future experimental and therapeutic targets. Depressed individuals with negative self-views may engage in brooding and devalue their experience of positivity.

Negative affect interference and fear of happiness are independently associated with depressive symptoms.

OBJECTIVES: Reward devaluation theory (RDT) posits that some depressed individuals avoid positivity due to its previous association with negative outcomes. Behavioral indicators of avoidance of reward support RDT, but self-report indicators have yet to be examined discriminantly. Two candidate self-report measures were examined in relation to depression: negative affect interference (NAI), or the experience of negative affect in response to positivity, and fear of happiness, a fear of prospective happiness. METHOD: Participants completed measures assessing NAI, fear of happiness scale, and depression online via Amazon's Mechanical Turk at three time points (N = 375). Multilevel modeling examined the relationship between NAI, fear of happiness, and depressive symptoms longitudinally. RESULTS: NAI and fear of happiness were both positively associated with depressive symptoms. They both uniquely predicted depressive symptoms when included within the same model. CONCLUSIONS: These findings suggest that different conceptualizations of positivity avoidance are uniquely associated with depressive symptoms.

Updating facial emotional expressions in working memory: Differentiating trait anxiety and depressiveness.

Individual differences in updating emotional facial expressions in working memory are not fully understood. Here we focused on the effects of high trait anxiety and high depressiveness in men and women on updating schematic emotional facial expressions (sad, angry, scheming, happy, neutral). A population representative sample of young adults was divided into four emotional disposition groups based on STAI-T and MADRS cut-offs: high anxiety (HA, n = 41), high depressiveness (HD, n = 31), high depressiveness & high anxiety (HAHD, n = 65) and control (CT, n = 155). Participants completed a 2-back task with schematic emotional faces, and valence/arousal ratings and verbal recognition tasks. A novel approach was used to separate encoding from retrieval. We found an interaction of emotional dispositions and emotional faces in updating accuracy. HD group made more errors than HA when encoding happy schematic faces. Other differences between emotional dispositions on updating measures were found but they were not specific to any emotional facial expression. Our findings suggest that there is a minor happy disadvantage in HD in contrast to HA which can be seen in lower accuracy for visual encoding of happy faces, but not in retrieval accuracy, the speed of updating, nor perception of emotional content in happy faces. These findings help to explain differences and similarities between high trait anxiety and high depressiveness in working memory and processing of facial expressions. The results are discussed in relation to prevalent theories of information processing in anxiety and depression.

Adolescent but not adult Sprague-Dawley rats display goal-directed responding after reward devaluation.

Alcohol drinking is typically initiated in adolescence, with use sometimes escalating to problematic levels. Escalation of drinking is often associated with a shift in drinking motives, with goal-directed initial use later transitioning to more habitual behavior. This study assessed whether adolescents are more sensitive than adults to habit formation when indexed via insensitivity to reward devaluation in an operant task for food reward. Adolescent and adult Sprague-Dawley rats were trained on either a random ratio (RR) or random interval (RI) schedule before undergoing devaluation. Adolescent animals on both schedules increased the number of lever presses across all training days. In contrast, adults in the RR group increased the number of lever presses across days whereas RI adults remained relatively stable. In response to pellet devaluation, only adolescents exhibited reduced responding, suggestive of goal-directed behavior, whereas no age differences were evident following control (home cage chow) devaluation. Contrary to our hypothesis, adolescents (but not adults) displayed goal-directed responding indexed via sensitivity to reward devaluation. These findings suggest that adolescents are not necessarily more likely to develop habits than adults, and hence other factors may contribute to the greater propensity of adolescents to engage in and escalate alcohol use.

Reward Devaluation Attenuates Cue-Evoked Sucrose Seeking and Is Associated with the Elimination of Excitability Differences between Ensemble and Non-ensemble Neurons in the Nucleus Accumbens.

Animals must learn relationships between foods and the environmental cues that predict their availability for survival. Such cue-food associations are encoded in sparse sets of neurons or "neuronal ensembles" in the nucleus accumbens (NAc). For these ensemble-encoded, cue-controlled appetitive responses to remain adaptive, they must allow for their dynamic updating depending on acute changes in internal states such as physiological hunger or the perceived desirability of food. However, how these neuronal ensembles are recruited and physiologically modified following the update of such learned associations is unclear. To investigate this, we examined the effects of devaluation on ensemble plasticity at the levels of recruitment, intrinsic excitability, and synaptic physiology in sucrose-conditioned Fos-GFP mice that express green fluorescent protein (GFP) in recently activated neurons. Neuronal ensemble activation patterns and their physiology were examined using immunohistochemistry and slice electrophysiology, respectively. Reward-specific devaluation following 4 d of ad libitum sucrose consumption, but not general caloric devaluation, attenuated cue-evoked sucrose seeking. This suggests that changes in the hedonic and/or incentive value of sucrose, and not caloric need, drove this behavior. Moreover, devaluation attenuated the size of the neuronal ensemble recruited by the cue in the NAc shell. Finally, it eliminated the relative enhanced excitability of ensemble (GFP+) neurons against non-ensemble (GFP-) neurons observed under non-devalued conditions, and did not induce any ensemble-specific changes in excitatory synaptic physiology. Our findings provide new insights into neuronal ensemble mechanisms that underlie the changes in the incentive and/or hedonic impact of cues that support adaptive food seeking.

Development of behavioural automaticity by extended Pavlovian training in an insect.

The effect of repetitive training on learned actions has been a major subject in behavioural neuroscience. Many studies of instrumental conditioning in mammals, including humans, suggested that learned actions early in training are goal-driven and controlled by outcome expectancy, but they become more automatic and insensitive to reduction in the value of the outcome after extended training. It was unknown, however, whether the development of value-insensitive behaviour also occurs by extended training of Pavlovian conditioning in any animals. Here we show that crickets Gryllus bimaculatus that had received minimal training to associate an odour with water (unconditioned stimulus, US) did not exhibit conditioned response (CR) to the odour when they were given water until satiation before the test, but those that had received extended training exhibited CR even when they were satiated with water. Further pharmacological experiments suggested that octopamine neurons, the invertebrate counterparts of noradrenaline neurons, mediate US value signals and control execution of CR after minimal training, but the control diminishes with the progress of training and hence the CR becomes insensitive to US devaluation. The results suggest that repetitive sensory experiences can lead to a change from a goal-driven response to a more automatic one in crickets.

Tract-Specific White Matter Correlates of Age-Related Reward Devaluation Deficits in Macaque Monkeys.

AIM: Cognitive aging is known to alter reward-guided behaviors that require interactions between the orbitofrontal cortex (OFC) and amygdala. In macaques, OFC, but not amygdala volumes decline with age and correlate with performance on a reward devaluation (RD) task. The present study used diffusion magnetic resonance imaging (dMRI) methods to investigate whether the condition of the white matter associated with amygdala-OFC connectivity changes with age and relates to reward devaluation. METHODS: Diffusion-, T1- and T2-weighted MRIs were acquired from adult and aged bonnet macaques. Using probabilistic tractography, fractional anisotropy (FA) estimates from two separate white matter tracts associated with amygdala-OFC connectivity, the uncinate fasciculus (UF) and amygdalofugal (AF) pathways, were obtained. Performance measures on RD and reversal learning (RL) tasks were also acquired and related to FA indices from each anatomical tract. RESULTS: Aged monkeys were impaired on both the RD and RL tasks and had lower FA indices in the AF pathway. Higher FA indices from the right hemisphere UF pathway correlated with better performance on an object-based RD task, whereas higher FA indices from the right hemisphere AF were associated with better performance on an object-free version of the task. FA measures from neither tract correlated with RL performance. CONCLUSIONS: These results suggest that the condition of the white matter connecting the amygdala and OFC may impact reward devaluation behaviors. Furthermore, the observation that FA indices from the UF and AF differentially relate to reward devaluation suggests that the amygdala-OFC interactions that occur via these separate tracts are partially independent.

Learning what to expect and when to expect it involves dissociable neural systems.

Two experiments with Long-Evans rats examined the potential independence of learning about different features of food reward, namely, "what" reward is to be expected and "when" it will occur. This was examined by investigating the effects of selective reward devaluation upon responding in an instrumental peak timing task in Experiment 1 and by exploring the effects of pre-training lesions targeting the basolateral amygdala (BLA) upon the selective reward devaluation effect and interval timing in a Pavlovian peak timing task in Experiment 2. In both tasks, two stimuli, each 60 s long, signaled that qualitatively distinct rewards (different flavored food pellets) could occur after 20 s. Responding on non-rewarded probe trials displayed the characteristic peak timing function with mean responding gradually increasing and peaking at approximately 20 s before more gradually declining thereafter. One of the rewards was then independently paired repeatedly with LiCl injections in order to devalue it whereas the other reward was unpaired with these injections. In a final set of test sessions in which both stimuli were presented without rewards, it was observed that responding was selectively reduced in the presence of the stimulus signaling the devalued reward compared to the stimulus signaling the still valued reward. Moreover, the timing function was mostly unaltered by this devaluation manipulation. Experiment 2 showed that pre-training BLA lesions abolished this selective reward devaluation effect, but it had no impact on peak timing functions shown by the two stimuli. It appears from these data that learning about "what" and "when" features of reward may entail separate underlying neural systems.

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.

Reward loss and the basolateral amygdala: A function in reward comparisons.

The neural circuitry underlying behavior in reward loss situations is poorly understood. We considered two such situations: reward devaluation (from large to small rewards) and reward omission (from large rewards to no rewards). There is evidence that the central nucleus of the amygdala (CeA) plays a role in the negative emotion accompanying reward loss. However, little is known about the function of the basolateral nucleus (BLA) in reward loss. Two hypotheses of BLA function in reward loss, negative emotion and reward comparisons, were tested in an experiment involving pretraining excitotoxic BLA lesions followed by training in four tasks: consummatory successive negative contrast (cSNC), autoshaping (AS) acquisition and extinction, anticipatory negative contrast (ANC), and open field testing (OF). Cell counts in the BLA (but not in the CeA) were significantly lower in animals with lesions vs. shams. BLA lesions eliminated cSNC and ANC, and accelerated extinction of lever pressing in AS. BLA lesions had no effect on OF testing: higher activity in the periphery than in the central area. This pattern of results provides support for the hypothesis that BLA neurons are important for reward comparison. The three affected tasks (cSNC, ANC, and AS extinction) involve reward comparisons. However, ANC does not seem to involve negative emotions and it was affected, whereas OF activity is known to involve negative emotion, but it was not affected. It is hypothesized that a circuit involving the thalamus, insular cortex, and BLA is critically involved in the mechanism comparing current and expected rewards.

Reward loss and addiction: Opportunities for cross-pollination.

Paradigms used to study the response to and consequences of exposure to reward loss have been underutilized in approaches to the psychobiology of substance use disorders. We propose here that bringing these two areas into contact will help expanding our understanding of both reward loss and addictive behavior, hence opening up opportunities for cross-pollination. This review focuses on two lines of research that point to parallels. First, several neurochemical systems involved in addiction are also involved in the modulation of the behavioral effects of reward loss, including opioid, GABA, and dopamine receptors. Second, there are extensive overlaps in the brain circuitry underlying both reward loss and addiction. Common components of this system include, at least, the amygdala, ventral and dorsal striatum, and various prefrontal cortex regions. Four emerging avenues of research that benefit from emphasis on the common ground between reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication. An understanding of the role of reward loss in addiction will point to a deeper understanding of the initiation and maintenance of substance use disorders.

Valor de la Recompensa: ¿Cómo y Para Qué se Usa el Concepto? / Value of the Reward: How Is the Concept Used and for What? / Valor de Recompensa: como e para que se usa o Conceito?

El escrito ofrece un panorama general sobre el valor de la recompensa, respondiendo los interrogantes: ¿qué es?, ¿cómo se ha conceptualizado? y ¿qué investigaciones han utilizado el concepto? En sentido general, este se utiliza para calificar una recompensa como más o menos efectiva: mientras mayor sea el valor, mayor es su eficacia. Primero se describe la medición histórica del valor y cómo lo define la literatura sobre economía conductual. A continuación aparecen dos usos diferentes del concepto: (a) como constructo hipotético y (b) como variable interviniente. También se incluyen definiciones operacionales, en las que no se definen exhaustivamente las variables asociadas, entonces no se le considera variable interviniente, pero tampoco se agrega significado, más allá del nivel de observación, por lo que no son ejemplo de constructo hipotético. Posteriormente se explora la relación entre demora del reforzador y descuento temporal. Las consideraciones finales retoman la discusión sobre su valor heurístico en la investigación contemporánea.

The article offers a general panorama on the value of the reward, answering the questions: What is it? How has it been conceptualized? What investigations have used the concept? In general, a reward is rated as more or less effective: the greater the value, the greater its efficiency. First, the article discusses the historical measurement of value and how the literature on behavioral economics defines it. Next, two different uses of the concept are presented: (a) as a hypothetical construct and (b) as intervening variable. The text includes operational definitions where the associated variables are not defined exhaustively and therefore not considered as intervening variable, but which also add no meaning beyond the level of observation and therefore are not an example of a hypothetical construct. The article then explores the relationship between delay of the reinforcing agent and temporal discount. Finally, the article considers the discussion about the concept's heuristic value in contemporary research.

Este texto oferece um panorama geral sobre o valor da recompensa ao responder aos questionamentos: o que é, como vem sendo conceituado e quais pesquisas têm utilizado o conceito? Em sentido geral, este se utiliza para qualificar uma recompensa como mais ou menos efetiva: quanto maior for o valor, maior será sua eficácia. Primeiramente, descreve-se a medição histórica do valor e como a literatura sobre economia comportamental o define. A seguir, aparecem dois usos diferentes do conceito: (a) como construto hipotético e (b) como variável interventora. Também são incluídas definições operacionais, nas quais não se definem exaustivamente as variáveis associadas, portanto não é considerada variável interventora nem se agrega significado mais além do nível de observação, razão pela qual não são exemplos de construto hipotético. Posteriormente, explora-se a relação entre demora do reforçador e desconto temporal. As considerações finais retomam a discussão sobre seu valor heurístico na pesquisa contemporânea.

Dorsomedial striatum lesions affect adjustment to reward uncertainty, but not to reward devaluation or omission.

The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. However, they showed normal negative contrast, acquisition under continuous reinforcement (CR), appetitive extinction, and response facilitation in early extinction trials. Open-field testing also indicated normal motor behavior. Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons.

Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes.

One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa. We find that large saccharin suppressors (large heroin takers) demonstrate increased mRNA expression for elements of the CRF signaling pathway (CRF, CRF receptors and CRF binding protein) within the hippocampus, medial prefrontal cortex and the ventral tegmental area. Moreover, there were no gene expression changes of these components in the nucleus accumbens. Use of bisulfite conversion sequencing suggests that changes in CRF binding protein and CRF receptor gene expression may be mediated by differential promoter methylation.