Objective: Various sources of evidence suggest that men and women differ in their experience of sexual pleasure. Such gender differences have been attributed to men\'s higher innate sex drive, supported by evolutionary psychology perspectives and gender differences in reproductive strategies. Method: This paper presents biopsychosocial evidence for gender similarities in the capacity to experience pleasure, and for substantial gender differences in opportunities for sexual pleasure. Results: We conclude that sexual activity, in most cultures, is less pleasurable and associated with greater cost for heterosexual women than for heterosexual men, even though they do not differ in the capacity for sexual pleasure. Conclusion: Since gender differences in experienced sexual pleasure are not a biological given, a more critical discourse of sexual pleasure might create awareness of current inequalities, help lift restrictions for women\'s opportunities for pleasure, and could reduce gender differences in the cost of sex. That would truly serve sexual justice around the globe.

While sign-tracking, also known as autoshaping, has been studied for many decades, only recently has the tendency to show sign-tracking behavior been linked to the development and persistence of addiction. Sign-tracking is dependent upon dopamine activity in the nucleus accumbens (NAc). The NAc is comprised predominantly of medium spiny projection neurons (MSN) that can be differentiated by their D1-like or D2-like dopamine receptor expression. Here we determined how reducing activity of D1-type MSNs in the NAc affects the expression and extinction of sign-tracking. To address this, we transfected the NAc of transgenic male and female rats that selectively express Cre recombinase in D1-type MSNs with a DIO viral vector expressing hM4Di. Cre- rats were given the same viral infusion but did not express the hM4Di receptor and therefore served as controls. Rats were then conditioned to associate lever presentations with pellet delivery. After sign-tracking was established, all rats were administered clozapine-n-oxide (CNO) prior to three additional conditioning sessions to assess the effects of NAc D1-MSNs inhibition on sign-tracking in the presence of reward. CNO treatment did not alter the expression of sign-tracking in Cre+ or Cre- rats. Next rats underwent extinction training where lever presentations occurred without pellet delivery and all rats received a CNO injection prior to each extinction session. In these extinction conditions, Cre+ rats exhibited robust extinction of sign-tracking across sessions, whereas Cre- rats did not. To determine if D1-MSN inhibition merely produced a temporary cessation of sign-tracking or instead had facilitated a persistent loss of sign-tracking, we evaluated the reemergence of sign-tracking in a test for reconditioning. During testing, reintroduction of the CS-US pairing did not promote the reemergence of sign-tracking in Cre+ rats, but restored sign-tracking in Cre- rats. Thus, chemogenetic inhibition of NAc D1-MSNs promoted extinction of sign-tracking. Collectively, these data suggest that D1-MSNs play an important role in resistance to extinction that typifies sign-tracking behavior.

UNASSIGNED: Anger can engender action by individuals and groups. It is thus important to understand anger\'s behavioral phenotypes and their underlying neural substrates. Here, we introduce a construct we term agentic anger, a negatively valenced internal state that motivates action to achieve risky goals. We evaluate our neurobehavioral model via testable hypotheses in two proof-of-concept studies.
UNASSIGNED: Study 1 used the Incentive Balloon Analogue Risk Task in a within-subjects, repeated measures design in 39 healthy volunteers to evaluate: (a) impact of blockade of reward on agentic anger, assessed by self-reports of negative activation (NA), (b) impact of achievement of reward on exuberance, assessed by self-reports of positive activation (PA), (c) the interrelationship of these valenced states, and (d) their relationship with personality.
UNASSIGNED: Task-induced NA was positively correlated with task-induced PA, risk-taking on the task and trait Social Potency (SP), a measure of trait agency and reward sensitivity on the Multidimensional Personality Questionnaire Brief-Form.
UNASSIGNED: Study 2 assessed functional MRI response to stakes for risk-taking in healthy volunteers receiving 20 mg d-amphetamine in a double-blinded, placebo-controlled crossover design (N = 10 males), providing preliminary information on ventral striatal response to risky rewards during catecholamine activation.
UNASSIGNED: Trait SP and task-induced PA were strongly positively related to catecholamine-facilitated BOLD response in the right nucleus accumbens, a brain region where DA prediction error signal shapes action value and selection. Participants\' task-induced NA was strongly positively related with trait SP and task-induced PA, replicating the findings of Study 1.
UNASSIGNED: Together these results inform the phenomenology and neurobiology of agentic anger, which recruits incentive motivational circuitry and motivates personal action in response to goals that entail risk (defined as exposure to uncertainty, obstacles, potential harm, loss and/or financial, emotional, bodily, or moral peril). Neural mechanisms of agency, anger, exuberance, and risk-taking are discussed, with implications for personal and group action, decision-making, social justice, and behavior change.

We review recent studies assessing the role of the bed nucleus of the stria terminalis (BNST) in the motivational control of instrumental conditioning. This evidence suggests that the BNST and central nucleus of the amygdala (CeA) form a circuit that modulates the ventral tegmental area (VTA) input to the nucleus accumbens core (NAc core) to control the influence of Pavlovian cues on instrumental performance. In support of these claims, we found that activity in the oval region of BNST was increased by instrumental conditioning, as indexed by phosphorylated ERK activity (Experiment 1), but that this increase was not due to exposure to the instrumental contingency or to the instrumental outcome per se (Experiment 2). Instead, BNST activity was most significantly incremented in a test conducted when the instrumental outcome was anticipated but not delivered, suggesting a role for BNST in the motivational effects of anticipated outcomes on instrumental performance. To test this claim, we examined the effect of NMDA-induced cell body lesions of the BNST on general Pavlovian-to-instrumental transfer (Experiment 3). These lesions had no effect on instrumental performance or on conditioned responding during Pavlovian conditioning to either an excitory conditioned stimulus (CS) or a neutral CS (CS0) but significantly attenuated the excitatory effect of the Pavlovian CS on instrumental performance. These data are consistent with the claim that the BNST mediates the general excitatory influence of Pavlovian cues on instrumental performance and suggest BNST activity may be central to CeA-BNST modulation of a VTA-NAc core circuit in incentive motivation.

BACKGROUND: Cocaine use disorder (CUD) is a highly heritable form of substance use disorder, with genetic variation accounting for a substantial proportion of the risk for transitioning from recreational use to a clinically impairing addiction. With repeated exposures to cocaine, psychomotor and incentive sensitization are observed in rodents. These phenomena are thought to model behavioral changes elicited by the drug that contribute to the progression into addiction, but little is known about how genetic variation may moderate these consequences.
OBJECTIVE: Here, we describe the use of two Collaborative Cross (CC) recombinant inbred mouse strains that either exhibit high (CC018/UncJ) or no (CC027/GeniUncJ) psychomotor sensitization in response to cocaine to measure phenotypes related to incentive sensitization after repeated cocaine exposures; given the relationship of incentive motivation to nucleus accumbens core (NAc) dopamine release and reuptake, we also assessed these neurochemical mechanisms.
METHODS: Adult male and female CC018/UncJ and CC027/GeniUncJ mice underwent Pavlovian conditioning to associate a visual cue with presentation of a palatable food reward, then received five, every-other-day injections of cocaine or vehicle. Following Pavlovian re-training, they underwent testing acquisition of a new operant response for the visual cue, now serving as a conditioned reinforcer. Subsequently, electrically evoked dopamine release was assessed using fast-scan cyclic voltammetry from acute brain slices containing the NAc.
RESULTS: While both strains acquired the Pavlovian association, only CC018/UncJ mice showed conditioned reinforcement and incentive sensitization in response to cocaine, while CC027/GeniUncJ mice did not. Voltammetry data revealed that CC018/UncJ, compared to CC027/GeniUnc, mice exhibited higher baseline dopamine release and uptake. Moreover, chronic cocaine exposure blunted tonic and phasic dopamine release in CC018/UncJ, but not CC027/GeniUncJ, mice.
CONCLUSIONS: Genetic background is a moderator of cocaine-induced neuroadaptations in mesolimbic dopamine signaling, which may contribute to both psychomotor and incentive sensitization and indicate a shared biological mechanism of variation.

Obesity and other eating disorders are marked by dysregulations to brain metabolic, hedonic, motivational, and sensory systems that control food intake. Classic approaches in hunger research have distinguished between hedonic and homeostatic processes, and have mostly treated these systems as independent. Hindbrain structures and a complex network of interconnected hypothalamic nuclei control metabolic processes, energy expenditure, and food intake while mesocorticolimbic structures are though to control hedonic and motivational processes associated with food reward. However, it is becoming increasingly clear that hedonic and homeostatic brain systems do not function in isolation, but rather interact as part of a larger network that regulates food intake. Incentive theories of motivation provide a useful route to explore these interactions. Adapting incentive theories of motivation can enable researchers to better understand how motivational systems dysfunction during disease. Obesity and addiction are associated with profound alterations to both hedonic and homeostatic brain systems that result in maladaptive patterns of consumption. A subset of individuals with obesity may experience pathological cravings for food due to incentive sensitization of brain systems that generate excessive \'wanting\' to eat. Further progress in understanding how the brain regulates hunger and appetite may depend on merging traditional hedonic and homeostatic concepts of food reward and motivation.

The following essay addresses the evolution of the term \"anhedonia\" as a key construct in biological psychiatry, especially as it pertains to positive emotional and motivational states central to mental health and well-being. In its strictest definition, anhedonia was intended to convey an inability to experience \"pleasure\" derived from ingestion of sweet tastes or the experience of pleasant odors and tactile sensations, among a host of positive sensations. However, this definition has proved to be too restrictive to capture the complexity of key psychological factors linked to major depression, schizophrenia, and substance use disorders it was originally intended to address. Despite the appeal of the elegant simplicity of the term anhedonia, its limitations soon became apparent when used to explain psychological constructs including aspects of learning, memory, and incentive motivation that are major determinants of success in securing the necessities of life. Accordingly, the definition of anhedonia has morphed into a much broader term that includes key roles in the disturbance of motivation in the form of anergia, impaired incentive motivation, along with deficits in associative learning and key aspects of memory, on which the ability to predict the consequences of one\'s actions are based. Here we argue that it is this latter capacity, namely predicting the likely consequences of motivated behavior, which can be termed \"anticipation,\" that is especially important in the key deficits implied by the general term anhedonia in the context of neuropsychiatric conditions.

BACKGROUND: Understanding the behavioral and neurobiological factors that render some individuals more susceptible than others to opioid addiction will be critical in combatting the opioid crisis.
OBJECTIVE: The purpose of the current study was to determine if behavioral traits associated with an increased likelihood to take and seek cocaine are the same traits that render one more susceptible to opioid-taking and opioid-seeking behavior. Individual differences in the acquisition of remifentanil self-administration and subsequent cue-induced reinstatement of remifentanil-seeking behavior were investigated using two animal models: the high-responder (HR)/low-responder (LR) and sign-tracker (ST)/goal-tracker (GT) models. Relative to LR rats, HR rats show increased novelty-induced locomotion or \"sensation-seeking\" behavior, and are more likely to acquire cocaine-taking behavior and do so at a faster rate. Relative to GT rats, ST rats attribute greater incentive motivational value to reward cues and are more likely to exhibit reinstatement of cocaine-seeking behavior.
RESULTS: In contrast to previous work using cocaine, we did not observe individual differences with respect to the acquisition of remifentanil self-administration- or cue-induced reinstatement of remifentanil-seeking behavior within the context of either the HR/LR or ST/GT model. Thus, neither the sensation-seeking trait nor the propensity to attribute incentive motivational value to reward cues predicts remifentanil-taking or remifentanil-seeking behavior.
CONCLUSIONS: These findings suggest that different traits may confer the initiation of opioid- vs. cocaine-taking behavior, and the propensity to relapse to opioid- vs. cocaine-seeking. Additional studies are needed to identify which neurobehavioral constructs confer liability to opioid use and relapse.

Binge-like eating behavior (BLE) has been characterized as an eating disorder in which subjects have an enhanced intake of food, mainly fats. However, intake of fats and carbohydrates may have differential effects on motivation. Previously it was shown that BLE produces an increase in operant responding for vegetable shortening, but others were unable to replicate the finding using sucrose as the reinforcer. Our aim was to determine if BLE behavior induced with a cafeteria-like diet (CaLD) with several options with fat content would produce an increment in performance. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE using CaLD options. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. Rats with intermittent access to CaLD options showed a clear BLE with an escalation in their intake; however they showed compensatory decrements of chow intake that rendered a similar body weight gain to a continuous access group. Although we were unable to observe an increase in BPs after BLE we were able to observe a protection against the decrements of BP previously observed with sugar. Different mechanisms for processing high fat and high carbohydrate reinforcers are variables worth exploring to gain a better understanding of BLE behavior in rodent models.

To survive in a complex environment, individuals form associations between environmental stimuli and rewards to organize and optimize reward seeking behaviors. The basolateral amygdala (BLA) uses these learned associations to inform decision-making processes. In this review, we describe functional projections between BLA and its cortical and striatal targets that promote learning and motivational processes central to decision-making. Specifically, we compare and contrast divergent projections from the BLA to the orbitofrontal (OFC) and to the nucleus accumbens (NAc) and examine the roles of these pathways in associative learning, value-guided decision-making, choice behaviors, as well as cue and context-driven drug seeking. Finally, we consider how these projections are involved in disorders of motivation, with a focus on Substance Use Disorder.