Molecular and Circuit-Dynamical Identification of Top-Down Neural Mechanisms for Restraint of Reward Seeking.

Reward-seeking behavior is fundamental to survival, but suppression of this behavior can be essential as well, even for rewards of high value. In humans and rodents, the medial prefrontal cortex (mPFC) has been implicated in suppressing reward seeking; however, despite vital significance in health and disease, the neural circuitry through which mPFC regulates reward seeking remains incompletely understood. Here, we show that a specific subset of superficial mPFC projections to a subfield of nucleus accumbens (NAc) neurons naturally encodes the decision to initiate or suppress reward seeking when faced with risk of punishment. A highly resolved subpopulation of these top-down projecting neurons, identified by 2-photon Ca2+ imaging and activity-dependent labeling to recruit the relevant neurons, was found capable of suppressing reward seeking. This natural activity-resolved mPFC-to-NAc projection displayed unique molecular-genetic and microcircuit-level features concordant with a conserved role in the regulation of reward-seeking behavior, providing cellular and anatomical identifiers of behavioral and possible therapeutic significance.

Reversing anterior insular cortex neuronal hypoexcitability attenuates compulsive behavior in adolescent rats.

Development of self-regulatory competencies during adolescence is partially dependent on normative brain maturation. Here, we report that adolescent rats as compared to adults exhibit impulsive and compulsive-like behavioral traits, the latter being associated with lower expression of mRNA levels of the immediate early gene zif268 in the anterior insula cortex (AIC). This suggests that underdeveloped AIC function in adolescent rats could contribute to an immature pattern of interoceptive cue integration in decision making and a compulsive phenotype. In support of this, we report that layer 5 pyramidal neurons in the adolescent rat AIC are hypoexcitable and receive fewer glutamatergic synaptic inputs compared to adults. Chemogenetic activation of the AIC attenuated compulsive traits in adolescent rats supporting the idea that in early stages of AIC maturity there exists a suboptimal integration of sensory and cognitive information that contributes to inflexible behaviors in specific conditions of reward availability.

Dissociated modulations of intranasal vasopressin on prosocial learning between reward-seeking and punishment-avoidance.

BACKGROUND: As an integral ingredient of human sociality, prosocial behavior requires learning what acts can benefit or harm others. However, it remains unknown how individuals adjust prosocial learning to avoid punishment or to pursue reward. Given that arginine vasopressin (AVP) is a neuropeptide that has been involved in modulating various social behaviors in mammals, it could be a crucial neurochemical facilitator that supports prosocial learning. METHODS: In 50 placebo controls and 54 participants with AVP administration, we examined the modulation of AVP on the prosocial learning characterized by reward and punishment framework, as well as its underlying neurocomputational mechanisms combining computational modeling, event-related potentials and oscillations. RESULTS: We found a self-bias that individuals learn to avoid punishment asymmetrically more severely than reward-seeking. Importantly, AVP increased behavioral performances and learning rates when making decisions to avoid losses for others and to obtain gains for self. These behavioral effects were underpinned by larger responses of stimulus-preceding negativity (SPN) to anticipation, as well as higher punishment-related feedback-related negativity (FRN) for prosocial learning and reward-related P300 for proself benefits, while FRN and P300 neural processes were integrated into theta (4-7 Hz) oscillation at the outcome evaluation stage. CONCLUSIONS: These results suggest that AVP context-dependently up-regulates altruism for concerning others' losses and reward-seeking for self-oriented benefits. Our findings provide insight into the selectively modulatory roles of AVP in prosocial behaviors depending on learning contexts between proself reward-seeking and prosocial punishment-avoidance.

Deep Brain Stimulation of the Medial Forebrain Bundle for Treatment-Resistant Depression: A Systematic Review Focused on the Long-Term Antidepressive Effect.

OBJECTIVE: Major depression affects millions of people worldwide and has important social and economic consequences. Since up to 30% of patients do not respond to several lines of antidepressive drugs, deep brain stimulation (DBS) has been evaluated for the management of treatment-resistant depression (TRD). The superolateral branch of the medial forebrain bundle (slMFB) appears as a "hypothesis-driven target" because of its role in the reward-seeking system, which is dysfunctional in depression. Although initial results of slMFB-DBS from open-label studies were promising and characterized by a rapid clinical response, long-term outcomes of neurostimulation for TRD deserve particular attention. Therefore, we performed a systematic review focused on the long-term outcome of slMFB-DBS. MATERIALS AND METHODS: A literature search using Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify all studies reporting changes in depression scores after one-year follow-up and beyond. Patient, disease, surgical, and outcome data were extracted for statistical analysis. The Montgomery-Åsberg Depression Rating Scale (ΔMADRS) was used as the clinical outcome, defined as percentage reduction from baseline to follow-up evaluation. Responders' and remitters' rates were also calculated. RESULTS: From 56 studies screened for review, six studies comprising 34 patients met the inclusion criteria and were analyzed. After one year of active stimulation, ΔMADRS was 60.7% ± 4%; responders' and remitters' rates were 83.8% and 61.5%, respectively. At the last follow-up, four to five years after the implantation, ΔMADRS reached 74.7% ± 4.6%. The most common side effects were stimulation related and reversible with parameter adjustments. CONCLUSIONS: slMFB-DBS appears to have a strong antidepressive effect that increases over the years. Nevertheless, to date, the overall number of patients receiving implantations is limited, and the slMFB-DBS surgical technique seems to have an important impact on the clinical outcome. Further multicentric studies in a larger population are needed to confirm slMFB-DBS clinical outcomes.

Regulation of Pv-specific interneurons in the medial prefrontal cortex and reward-seeking behaviors.

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model. We hypothesize that Pv-FSI activation elicits changes in cortical glutamate levels and reward-seeking behaviors. To determine molecular and behavioral effects of Pv-FSI, we performed microdialysis and operant conditioning tasks for sucrose and alcohol rewards. In addition, we also examined how alcohol reward itself affects Pv-FSI functioning. Interestingly, our microdialysis results demonstrate that alcohol exposure inhibits Pv-FSI functioning in the medial prefrontal cortex (mPFC) and this consequently can regulate glutamate levels downstream in the nucleus accumbens. For sucrose reward-seeking behaviors, Pv-FSI activation in the mPFC increases sucrose self-administration whereas it does not promote alcohol seeking. For alcohol rewards, however, Pv-FSI activation in the mPFC results in increased compulsive head entry in operant chambers during devaluation procedures. Overall, our results suggest that not only do Pv-FSI contribute to changes in the cortical microcircuit and reward-seeking behaviors but also that alcohol affects Pv-FSI neurotransmission. Therefore, Pv-FSI has prompted interest in their role in maintaining a balance in neuronal excitation/inhibition and in regulating reward-seeking processes such as compulsivity, all of which are important factors for excessive alcohol seeking.

Self-Report Measures of Anhedonia and Approach Motivation Weakly Correspond to Anhedonia and Depression Assessed via Clinical Interviews.

Self-report scales are popular tools for measuring anhedonic experiences and motivational deficits, but how well do they reflect clinically significant anhedonia? Seventy-eight adults participated in face-to-face structured diagnostic interviews: 22 showed clinically significant anhedonia, and 18 met criteria for depression. Analyses of effect sizes comparing the anhedonia and depression groups to their respective controls found large effects, as expected, for measures of depressive symptoms, but surprisingly weak effect sizes (all less than d=.50) for measures of general, social, or physical anhedonia, behavioral activation, and anticipatory and consummatory pleasure. Measures of Neuroticism and Extraversion distinguished the anhedonic and depressed groups from the controls at least as well as measures of anhedonia and motivation. Taken together, the findings suggest that caution is necessary when extending self-report findings to populations with clinically significant symptoms.

Viscoelasticity of reward and control systems in adolescent risk taking.

Heightened risk-taking tendencies during adolescence have been hypothesized to be attributable to physiological differences of maturation in key brain regions. The socioemotional system (e.g., nucleus accumbens), which is instrumental in reward response, shows a relatively earlier development trajectory than the cognitive control system (e.g., medial prefrontal cortex), which regulates impulse response. This developmental imbalance between heightened reward seeking and immature cognitive control potentially makes adolescents more susceptible to engaging in risky activities. Here, we assess brain structure in the socioemotional and cognitive control systems through viscoelastic stiffness measured with magnetic resonance elastography (MRE) and volumetry, as well as risk-taking tendencies measured using two experimental tasks in 40 adolescents (mean age â€‹= â€‹13.4 years old). MRE measures of regional brain stiffness reflect brain health and development via myelin content and glial matrix makeup, and have been shown to be highly sensitive to cognitive processes as compared to measures of regional brain volume and diffusion weighted imaging metrics. We find here that the viscoelastic and volumetric differences between the nucleus accumbens and the prefrontal cortex are correlated with increased risk-taking behavior in adolescents. These differences in development between the two brain systems can be used as an indicator of those adolescents who are more prone to real world risky activities and a useful measure for characterizing response to intervention.

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents.

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic-pituitary-adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity-focusing on serum corticosterone (CORT)-and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

Choice for Drug or Natural Reward Engages Largely Overlapping Neuronal Ensembles in the Infralimbic Prefrontal Cortex.

Cue-reward associations form distinct memories that can drive appetitive behaviors and are involved in craving for both drugs and natural rewards. Distinct sets of neurons, so-called neuronal ensembles, in the infralimbic area (IL) of the medial prefrontal cortex (mPFC) play a key role in alcohol seeking. Whether this ensemble is specific for alcohol or controls reward seeking in general remains unclear. Here, we compared IL ensembles formed upon recall of drug (alcohol) or natural reward (saccharin) memories in male Wistar rats. Using an experimental framework that allows identification of two distinct reward-associated ensembles within the same animal, we found that cue-induced seeking of either alcohol or saccharin activated ensembles of similar size and organization, whereby these ensembles consist of largely overlapping neuronal populations. Thus, the IL seems to act as a general integration hub for reward seeking behavior, but also contains subsets of neurons that encode for the different rewards.SIGNIFICANCE STATEMENT Cue-reward associations form distinct memories that can act as drivers of appetitive behaviors and are involved in craving for natural rewards as well as for drugs. Distinct sets of neurons, so-called neuronal ensembles, in the infralimbic area of the mPFC play a key role in cue-triggered reward seeking. However, it is unclear whether these ensembles act as broadly tuned controllers of approach behavior or represent the learned associations between specific cues and rewards. Using an experimental framework that allows identification of two distinct reward-associated ensembles within the same animal we find largely overlapping neuronal populations. Repeated activation by two distinct events could reflect the linking of the two memory traces within the same neuron.

Increased Maternal Care Rescues Altered Reinstatement Responding Following Moderate Prenatal Alcohol Exposure.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) commonly include deficits in learning, memory, and executive control that can have a severe negative impact on quality of life across the life span. It is still unclear how prenatal alcohol exposure (PAE) affects executive control processes, such as control over reward seeking, that lead to inappropriate behavior later in life. Learning and reinstatement of a previously learned response after extinction is a simple, well-validated measure of both acquisition of a rewarded instrumental response and sensitivity to reward and reward-associated cues. We investigated the effects of PAE on learning, extinction, and reinstatement of a simple instrumental response for food reward. Next, we assessed the effectiveness of an early intervention, communal nest (CN) housing, on increased reinstatement of an extinguished response seen after PAE. METHODS: To assess the effects of PAE on control over reward seeking, we tested male and female PAE and saccharine (SAC) controls raised in a standard nest (SN) on the acquisition, extinction, and food reward-induced reinstatement of an instrumental response utilizing a touch screen-based paradigm. Next, in order to examine the effects of an early-life intervention on these behaviors, we tested PAE and SAC mice raised in a CN early-life environment on these behaviors. RESULTS: PAE mice readily acquired and extinguished a simple touch response to a white square stimulus. However, PAE mice showed significantly increased and persistent reinstatement compared to controls. Increased maternal care via rearing in CN slowed acquisition and sped extinction learning and rescued the significantly increased reinstatement responding in PAE mice. CONCLUSIONS: Together these results demonstrate that even moderate PAE is sufficient to alter control over reward seeking as measured by reinstatement. Importantly, an early-life intervention previously shown to improve cognitive outcomes in PAE mice was sufficient to ameliorate this effect.

Dopamine invigorates reward seeking by promoting cue-evoked excitation in the nucleus accumbens.

Approach to reward is a fundamental adaptive behavior, disruption of which is a core symptom of addiction and depression. Nucleus accumbens (NAc) dopamine is required for reward-predictive cues to activate vigorous reward seeking, but the underlying neural mechanism is unknown. Reward-predictive cues elicit both dopamine release in the NAc and excitations and inhibitions in NAc neurons. However, a direct link has not been established between dopamine receptor activation, NAc cue-evoked neuronal activity, and reward-seeking behavior. Here, we use a novel microelectrode array that enables simultaneous recording of neuronal firing and local dopamine receptor antagonist injection. We demonstrate that, in the NAc of rats performing a discriminative stimulus task for sucrose reward, blockade of either D1 or D2 receptors selectively attenuates excitation, but not inhibition, evoked by reward-predictive cues. Furthermore, we establish that this dopamine-dependent signal is necessary for reward-seeking behavior. These results demonstrate a neural mechanism by which NAc dopamine invigorates environmentally cued reward-seeking behavior.

Navigating the complex terrain of motivated behavior: a bibliometric and neuroscientific perspective.

Over several decades, motivated behavior has emerged as a crucial study area within neuroscience. Understanding the neural substrates and mechanisms driving behaviors related to reward, addiction, and other motivation forms is pivotal for novel therapeutic interventions. This review provides a bibliometric analysis of the literature, highlighting the main trends, influential authors, and the potential future direction of the field. Utilizing a dataset comprised by 3,150 publications from the Web of Science and Scopus databases ("motivated behavior as query), we delve into key metrics like publication trends, keyword prevalence, author collaborations, citation impacts, and employed an unsupervised natural language processing technique - Latent Dirichlet Allocation - for topic modeling. From early investigations focusing on basic neural mechanism and behaviors in animal models to more recent studies exploring the complex interplay of neurobiological, psychological, and social factors in humans, the field had undergone a remarkable transformation. The last century has seen a proliferation of research dedicated to uncovering the intricacies of motivation, significantly enriching our understanding of its myriad implications for human behavior and mental health. This bibliometric analysis aims to offer comprehensive insights into this dynamic research area, highlighting the field's key contributions and potential future directions, thereby serving as a valuable resource for researchers, and hopefully give a more thorough understanding of the research area.

Less bang for my buck: Diminished anticipated enjoyment contributes to dysphoria-linked deficit in activity behavioural engagement choice.

This study experimentally investigated the role of anticipated enjoyment and effort in mediating dysphoria-related deficit in activity engagement behavioural choice. Using a novel activity information processing task (about a fictional "new" Nintendo Wii sports game called "Tornado Ball"), N = 249 participants (n = 95 High Dysphoria; n = 154 Low Dysphoria) were presented information about the benefits (enjoyable features) and costs (mental and physical effort barriers) as product reviews from another player. The order of cost vs. benefit information was manipulated such that participants either heard cost information before benefit information, or vice versa. They then rated what their anticipated enjoyment and effort will be if they were to play Tornado Ball, before being given the opportunity to choose to try it themselves or not. The High Dysphoria group reported lower anticipated enjoyment (but not higher effort) relative to the Low Dysphoria group, but only when cost information was presented first. Importantly, a moderated mediation showed that the High Dysphoria group reported lower tendency to choose activity engagement (game play) as a function of having lower anticipated enjoyment, but only when cost information was presented first. The present finding indicate that reduced anticipated enjoyment may causally contribute to dysphoria-linked deficits in activity engagement behavioural choice.

Sign-tracking to non-drug reward is related to severity of alcohol-use problems in a sample of individuals seeking treatment.

BACKGROUND: A prominent neuroscientific theory of drug addiction is the incentive sensitization model. Individual differences in the tendency to ascribe motivational salience to cues that predict reward, and involuntary "sign-tracking" (orientation towards) such cues have been identified as potentially important in understanding vulnerability to addiction and relapse. However, to date this behaviour has not been assessed in a treatment-seeking clinical population, who typically represent those most susceptible to alcohol-related harms and episodes of relapse. This highlights a significant gap in the literature pertaining to incentive sensitization and drug dependence. METHODS: Individuals accessing inpatient drug and alcohol services with alcohol as primary drug of concern were recruited to participate in a Cognitive Bias Modification (CBM) intervention. At the baseline assessment, participants completed various self-report measures (including the Alcohol Use Disorders Identification Test; AUDIT) in addition to a visual search task measuring sign-tracking to cues signalling monetary reward. At 3-month follow up, abstinence from alcohol was the primary outcome measure. All analyses and hypotheses were pre-registered. RESULTS: At baseline (57 participants), AUDIT scores correlated with sign-tracking to signals of monetary reward. In a subsequent regression analysis sign-tracking, gender and self-reported alcohol craving predicted abstinence at 3-month follow up (41 participants). CONCLUSIONS: Our work demonstrates that involuntary sign-tracking to cues signalling non-drug reward is associated with problematic alcohol use and return to use at 3-month follow up, in a treatment-seeking sample. Whether this automatic prioritisation of cues signalling reward is a consequence or vulnerability for problematic alcohol use remains to be investigated.

Two Distinct Neuronal Populations in the Rat Parafascicular Nucleus Oppositely Encode the Engagement in Stimulus-driven Reward-seeking.

BACKGROUND: The thalamus is a phylogenetically well-preserved structure. Known to densely contact cortical regions, its role in the transmission of sensory information to the striatal complex has been widely reconsidered in recent years. METHODS: The parafascicular nucleus of the thalamus (Pf) has been implicated in the orientation of attention toward salient sensory stimuli. In a stimulus-driven reward-seeking task, we sought to characterize the electrophysiological activity of Pf neurons in rats. RESULTS: We observed a predominance of excitatory over inhibitory responses for all events in the task. Neurons responded more strongly to the stimulus compared to lever-pressing and reward collecting, confirming the strong involvement of the Pf in sensory information processing. The use of long sessions allowed us to compare neuronal responses to stimuli between trials when animals were engaged in action and those when they were not. We distinguished two populations of neurons with opposite responses: MOTIV+ neurons responded more intensely to stimuli followed by a behavioral response than those that were not. Conversely, MOTIV- neurons responded more strongly when the animal did not respond to the stimulus. In addition, the latency of excitation of MOTIV- neurons was shorter than that of MOTIV+ neurons. CONCLUSION: Through this encoding, the Pf could perform an early selection of environmental stimuli transmitted to the striatum according to motivational level.

Choice impulsivity after repeated social stress is associated with increased perineuronal nets in the medial prefrontal cortex.

Repeated stress can predispose to substance abuse. However, behavioral and neurobiological adaptations that link stress to substance abuse remain unclear. This study investigates whether intermittent social defeat (ISD), a stress protocol that promotes drug-seeking behavior, alters intertemporal decision-making and cortical inhibitory function in the medial prefrontal cortex (mPFC). Male long evans rats were trained in a delay discounting task (DDT) where rats make a choice between a fast (1 s) small reward (1 sugar pellet) and a large reward (3 sugar pellets) that comes with a time delay (10 s or 20 s). A decreased preference for delayed rewards was used as an index of choice impulsivity. Rats were exposed to ISD and tested in the DDT 24 h after each stress episode, and one- and two-weeks after the last stress episode. Immunohistochemistry was performed in rat's brains to evaluate perineuronal nets (PNNs) and parvalbumin GABA interneurons (PV) labeling as markers of inhibitory function in mPFC. ISD significantly decreased the preference for delayed large rewards in low impulsive, but not high impulsive, animals. ISD also increased the density of PNNs in the mPFC. These results suggest that increased choice impulsivity and cortical inhibition predispose animals to seek out rewards after stress.

Effects of adolescent ethanol exposure on adult nondrug reward seeking behavior in male and female mice.

BACKGROUND: Adolescent alcohol use is associated with an increased likelihood of developing an alcohol use disorder in adulthood, potentially due to the effects of alcohol exposure on reward-seeking behavior. However, it remains unclear whether adolescent drinking is sufficient to alter nondrug reward seeking in adulthood. As adolescence is a period of both brain and sexual maturation, which occur in a sex-dependent manner, males and females may be differentially sensitive to the consequences of adolescent alcohol exposure. The present study investigated whether adolescent ethanol exposure affected food reward taking and seeking in male and female adult mice. METHODS: Male and female C57BL/6J mice underwent intermittent ethanol exposure (AIE) via vapor inhalation during early adolescence (28-42 days of age). At 10 weeks of age, the mice were trained in a conditioned place preference paradigm (CPP) for a food reward. We measured food consumption, CPP, and cFos expression in multiple brain regions following CPP testing. Data were analyzed using repeated measures analysis of variance with exposure (air vs. AIE), sex, and time as factors. RESULTS: AIE exposure increased food consumption during CPP training in adult male mice, but reduced pellet consumption in adult female mice. AIE exposure impaired CPP expression only in female mice. Despite these behavioral differences, exposure to the reward-paired chamber did not induce differential cFos expression following CPP testing in the prelimbic and infralimbic cortices or the nucleus accumbens core and shell. CONCLUSION: These findings indicate that adolescent ethanol exposure disrupted nondrug reward taking and seeking in adulthood in female mice and altered consumption in adult male mice.

Hormone sensitivity predicts the beneficial effects of transdermal estradiol on reward-seeking behaviors in perimenopausal women: A randomized controlled trial.

Depression is highly prevalent during the menopause transition (perimenopause), and often presents with anxious and anhedonic features. This increased vulnerability for mood symptoms is likely driven in part by the dramatic hormonal changes that are characteristic of the menopause transition, as prior research has linked fluctuations in estradiol (E2) to emergence of depressed mood in at risk perimenopausal women. Transdermal estradiol (TE2) has been shown to reduce the severity of depression in clinically symptomatic women, particularly in those with recent stressful life events. This research extends prior work by examining the relation between E2 and reward seeking behaviors, a precise behavioral indicator of depression. Specifically, the current study utilizes a randomized, double blind, placebo-controlled design to investigate whether mood sensitivity to E2 flux ("hormone sensitivity") predicts the beneficial effects of TE2 interventions on reward seeking behaviors in perimenopausal women, and whether recent stressful life events moderate any observed associations. METHOD: Participants were 66 women who met standardized criteria for being early or late perimenopausal based on bleeding patterns. Participants were recruited from a community sample; therefore, mood symptoms varied across the continuum and the majority of participants did not meet diagnostic criteria for a depressive or anxiety disorder at the time of enrollment. Hormone sensitivity was quantified over an 8-week baseline period, using within-subjects correlations between repeated weekly measures of E2 serum concentrations and weekly anxiety (State Trait Anxiety Inventory) and anhedonia ratings (Snaith-Hamilton Pleasure Scale). Women were then randomized to receive 8 weeks of TE2 (0.1 mg) or transdermal placebo, and reward-seeking behaviors were assessed using the Effort-Expenditure for Rewards Task (EEfRT). RESULTS: Participants who were randomized to receive transdermal estradiol and who demonstrated greater anxiety sensitivity to E2 fluctuations at baseline, demonstrated more reward seeking behaviors on the EEfRT task. Notably, the strength of the association between E2-anxiety sensitivity and post-randomization EEfRT for TE2 participants increased when women experienced more recent stressful life events and rated those events as more stressful. E2-anhedonia sensitivity was not associated with reward-seeking behaviors. CONCLUSION: Perimenopausal women who are more sensitive to E2 fluctuations and experienced more recent life stress may experience a greater benefit of TE2 as evidenced by an increase in reward seeking behaviors.

The role of sex on sign-tracking acquisition and outcome devaluation sensitivity in Long Evans rats.

Cues that predict rewards can trigger reward-seeking behaviors but also can, in some cases, become targets of motivation themselves. One behavioral phenomenon that captures this idea is sign-tracking in which animals, including humans, interact with reward-predictive cues even though it is not necessary to do so. Sign-tracking in rats has been studied in the domain of motivation and in how motivated behaviors can or cannot become excessive and habit-like over time. Many prior studies look at sign-tracking examine this behavior in male subjects, but there are few papers that look at this behavior in female subjects. Moreover, it is unknown where there might be sex-related variation in how flexible sign-tracking is when faced with changing reward values. Therefore, we asked if there were sex differences in the acquisition of sign-tracking behavior and if there were any sex differences in how sensitive animals were in their sign-tracking following reward devaluation. In contrast to previous reports, we found that males and females show no differences in how they acquire sign-tracking and in ultimate sign-tracking levels following training. Additionally, we found no difference in how quickly males and females learned to devalue the food reward, and we found no differences in sign-tracking levels by sex following outcome devaluation. We believe that this is primarily due to our experiment being performed in the Long Evans strain but also believe that there are many other factors contributing to differences between our study and previous work.

Still a "hidden island"? The rodent insular cortex in drug seeking, reward, and risk.

The insular cortex (IC) is implicated in risky decision making and drug-seeking behaviors, in a manner dissociable from natural reward seeking. However, evidence from rodent studies of motivated behaviors suggests that the role of the IC is not always consistent across procedures. Moreover, there is evidence of dissociation of function between posterior (pIC) and anterior (aIC) subregions in these behaviors. Under which circumstances, and by which mechanisms, these IC subregions are recruited to regulate motivated behaviors remains unclear. Here, we discuss evidence of rodent pIC and aIC function across drug-related behaviors, natural reward seeking, and decision making under risk and highlight procedural differences that may account for seemingly conflicting findings. Although gaps in the literature persist, we hypothesize that IC activity is broadly important for selection of appropriate behaviors based on learned action-outcome contingencies and that associated risk is sufficient, but not necessary, to recruit the aIC in reward seeking without involving the pIC.