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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.

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Copy number variants (CNVs) are robustly associated with psychiatric disorders and their dimensions and changes in brain structures and behavior. However, as CNVs contain many genes, the precise gene-phenotype relationship remains unclear. Although various volumetric alterations in the brains of 22q11.2 CNV carriers have been identified in humans and mouse models, it is unknown how the genes in the 22q11.2 region individually contribute to structural alterations and associated mental illnesses and their dimensions. Our previous studies have identified Tbx1, a T-box family transcription factor encoded in 22q11.2 CNV, as a driver gene for social interaction and communication, spatial and working memory, and cognitive flexibility. However, it remains unclear how TBX1 impacts the volumes of various brain regions and their functionally linked behavioral dimensions. In this study, we used volumetric magnetic resonance imaging analysis to comprehensively evaluate brain region volumes in congenic Tbx1 heterozygous mice. Our data show that the volumes of anterior and posterior portions of the amygdaloid complex and its surrounding cortical regions were reduced in Tbx1 heterozygous mice. Moreover, we examined the behavioral consequences of an altered volume of the amygdala. Tbx1 heterozygous mice were impaired for their ability to detect the incentive value of a social partner in a task that depends on the amygdala. Our findings identify the structural basis for a specific social dimension associated with loss-of-function variants of TBX1 and 22q11.2 CNV.

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There are numerous evidence showing that cadmium (Cd) is an endocrine disruptor that exerts multiple toxic effects at different reproductive levels, including male sexual behavior (MSB). The effect of early exposure to Cd on sexual incentive motivation (SIM) and MSB in adult stage, and the immunoreactivity of receptors for hormones such as estrogens and androgens in brain regions that are relevant for the SIM and MSB display, have not been studied until now. The present study evaluated the effects of 0.5 and 1 mg/kg CdCl2 from day 1-56 of postnatal life on SIM and MSB in adults rats, as well as serum testosterone concentrations, Cd concentration in blood, testis, and brain areas, and the immunoreactivity in estrogen receptors (ER-α and -ß), and androgen receptor (AR) in the olfactory bulbs (OB), medial preoptic area (mPOA), and medial amygdala (MeA). Our results showed that both doses of Cd decreased SIM and MSB, accompanied by low serum concentrations of testosterone. Also, there was a significant reduction in immunoreactivity of ER-α and AR in mPOA, and a significant reduction in AR in MeA on male rats treated with Cd 1 mg/kg. These results show that exposure to high doses of Cd in early postnatal life could alter the correct integration of hormonal signals in the brain areas that regulate and display SIM and MSB in adult male rats.

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This study investigated the effect of material incentive motivation on the working memory performance of kindergartners using a large-scale randomized controlled trial covering 7123 children aged 50 to 144 months (M = 75.85 months) from 19 provinces in Thailand. This study measured the working memory of young children using the digit span task. The first finding is that material incentive motivation raised the working memory performance of young children by 4% of the mean of the control group. The second finding is that young children with different background characteristics responded to material incentive motivation uniformly except for the children's age. The third finding is that school readiness was the most predictive variable for the working memory performance of young children.

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Introduction: 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. Study 1 Methods: 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. Study 1 Results: 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. Study 2 Methods: 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. Study 2 Results: 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. Discussion: 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.

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RATIONALE: 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. OBJECTIVES: 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.

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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.

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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.

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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.

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RATIONALE: 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.

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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.

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Resumen Introducción y objetivo: Los procesos de aprendizaje y motivación han sido centrales para la comprensión de los mecanismos que subyacen al tabaquismo. En particular, existe evidencia creciente sobre la importancia de valores motivacionales de incentivo para entender el inicio y mantenimiento del tabaquismo. El objetivo general de este experimento fue evaluar el papel de la nicotina aguda sobre el valor de incentivo de una recompensa natural, (comida) asociada con un estímulo ambiental, (palanca experimental). Método: Se utilizaron ratas Wistar. Se administró nicotina (0.4 mg/kg) de manera aguda en momentos específicos del entrenamiento, utilizando un procedimiento de diez sesiones de adquisición y cuatro sesiones extinción en una tarea pavloviana de automoldeamiento. El diseño experimental incluyó tres grupos, el grupo control de solución salina y grupos de nicotina durante la adquisición y la extinción. Resultados: Se encontró que la administración aguda de nicotina, de manera específica y en comparación con los otros dos grupos experimentales, resultó en un efecto de retardo durante la fase de extinción, y que una administración similar de nicotina no resultó en efectos observables durante el desempeño comportamental en adquisición. Conclusiones: Estos resultados apoyan el papel de la nicotina como fortalecedora del valor de incentivo de las claves ambientales durante la extinción para una tarea de automoldeamiento.

Abstract Introduction and goal: Learning and motivational processes have been central for a modern understanding of tobacco addiction. There is evidence that supports the importance of incentive motivational processes for the maintenance of tobacco addiction. The main goal of the present experiment was to evaluate the effects of acute nicotine on the incentive value of a natural reward, (food) paired with an environmental cue (pressing lever). Method: Wistar rats were used. Accute nicotine (0.4 mg/kg) was administered on key sessions, using a pavlovian autoshaping procedure involving ten acquisition and four extinction sessions. The experimental design included three groups, a saline administration control group and groups with specific nicotine administration during either acquisition or extinction. Results: We found that acute administration of nicotine, in contrast with saline only or previous nicotine administration during acquisition, had an enhancing effect on responding for the environmental cue during autoshaping extinction, but we did not find evidence that acute nicotine affected acquisition performance. Conclusion: Our results are consistent with a role of nicotine enhancing the incentive value of stimuli during extinction from a pavlovian autoshaping task.

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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.

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BACKGROUND: Corticotropin-releasing factor (CRF) neural systems are important stress mechanisms in the central amygdala (CeA), bed nucleus of stria terminalis (BNST), nucleus accumbens (NAc), and related structures. CRF-containing neural systems are traditionally posited to generate aversive distress states that motivate overconsumption of rewards and relapse in addiction. However, CRF-containing systems may alternatively promote incentive motivation to increase reward pursuit and consumption without requiring aversive states. METHODS: We optogenetically stimulated CRF-expressing neurons in the CeA, BNST, or NAc using Crh-Cre+ rats (n = 37 female, n = 34 male) to investigate roles in incentive motivation versus aversive motivation. We paired CRF-expressing neuronal stimulations with earning sucrose rewards in two-choice and progressive ratio tasks and investigated recruitment of distributed limbic circuitry. We further assessed valence with CRF-containing neuron laser self-stimulation tasks. RESULTS: Channelrhodopsin excitation of CRF-containing neurons in the CeA and NAc amplified and focused incentive motivation and recruited activation of mesocorticolimbic reward circuitry. CRF systems in both the CeA and NAc supported laser self-stimulation, amplified incentive motivation for sucrose in a breakpoint test, and focused "wanting" on laser-paired sucrose over a sucrose alternative in a two-choice test. Conversely, stimulation of CRF-containing neurons in the BNST produced negative valence or aversive effects and recruited distress-related circuitry, as stimulation was avoided and suppressed motivation for sucrose. CONCLUSIONS: CRF-containing systems in the NAc and CeA can promote reward consumption by increasing incentive motivation without involving aversion. In contrast, stimulation of CRF-containing systems in the BNST is aversive but suppresses sucrose reward pursuit and consumption rather than increase, as predicted by traditional hedonic self-medication hypotheses.

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Irisin is a novel myokine/adipokine that is released into the circulation in response to types of exercise and increases energy expenditure. Disorders in the endocrine system related to reproduction, which occur due to the chronic or excessive exercise, cause a decrease in women's sexual desire. However, the role of irisin hormone on sexual desire in women has not been elucidated. We hypothesized that chronic irisin exposure would decrease sexual incentive motivation for male partners by affecting the endocrine system in female rats. We tested this by quantifying and comparing of both sexual incentive motivation and active investigation for sexual partner, and also changes in the serum hormone levels in chronically irisin-treated female rats. As a result, chronic irisin exposure decreased the time spent near the male rat, male preference ratio, and male investigation preference ratio. Furthermore, serum testosterone and progesterone levels significantly decreased and estradiol levels increased while kisspeptin-1 levels were not changed by chronic irisin exposure in female rats. These data indicate that chronic irisin exposure may cause low sexual incentive motivation for opposite-sex partners in female rats via changes in reproductive hormones. The results suggest that irisin hormone may play a role in decreased sexual desire due to long-term exercise in women.

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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.

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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. Our aim was to determine if BLE behavior induced with a sucrose solution would produce an increment in performance for sucrose reinforcers. Male Wistar rats were trained under an exponential progressive ratio schedule of sucrose reinforcement; thereafter, the limited access model was used to induce BLE. Finally, subjects were tested for increments in break points (BPs) in the progressive ratio schedule. We were unable to observe an increase in BPs after BLE. No increments in BPs were observed when a distinctive flavor (vanilla-flavored sucrose) was correlated with BLE induction and reinforcement, or when different types of ratio progression in the operant schedules were employed. However, rats adjusted their BPs according to reinforcer concentration after BLE induction, demonstrating that valuation (cost/benefit decision) of reinforcers was intact. Extent of training, alterations of reward processing after extended exposure to sucrose, and 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.

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A goal in addiction research is to distinguish forms of neuroplasticity that are involved in the transition to addiction from those involved in mere drug taking. Animal models of drug self-administration are essential in this context. Here, we compared in male rats two cocaine self-administration procedures that differ in the extent to which they evoke addiction-like behaviours. We measured both incentive motivation for cocaine using progressive ratio procedures, and cocaine-induced c-fos mRNA expression, a marker of neuronal activity. Rats self-administered intravenous cocaine (0.25 mg/kg/infusion) for seven daily 6-hour sessions. One group had intermittent access (IntA; 6 minutes ON, 26 min OFF × 12) to rapid infusions (delivered over 5 s). This models the temporal kinetics of human cocaine use and produces robust addiction-like behaviour. The other group had Long access (LgA) to slower infusions (90 s). This produces high levels of intake without promoting robust addiction-like behaviour. LgA-90 s rats took twice as much cocaine as IntA-5 s rats did, but IntA-5 s rats showed greater incentive motivation for the drug. Following a final self-administration session, we quantified c-fos mRNA expression in corticostriatal regions. Compared to LgA-90 s rats, IntA-5 s rats had more cocaine-induced c-fos mRNA in the orbitofrontal and prelimbic cortices and the caudate-putamen. Thus, a cocaine self-administration procedure (intermittent intake of rapid infusions) that promotes increased incentive motivation for the drug also enhances cocaine-induced gene regulation in corticostriatal regions. This suggests that increased drug-induced recruitment of these regions could contribute to the neural and behavioural plasticity underlying the transition to addiction.

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BACKGROUND: Pavlovian stimuli can influence instrumental behaviors via phenomena such as Pavlovian-to-instrumental transfer (PIT). PIT arises via dissociable processes as sensory-specific PIT (SS-PIT) and general PIT. The basolateral amygdala (BLA) mediates SS-PIT, but not general PIT. However, the specific BLA neuronal populations involved are unknown. AIMS: To determine the contribution of glutamatergic BLA neurons to the expression of SS-PIT and to the recall of sensory-specific properties of stimulus-outcome associations. METHODS: BLA neurons were transduced with virus containing either GFP or hM4Di, driven by the CamKII promoter. Rats were then tested for SS and general PIT and subsequently for expression of Pavlovian outcome devaluation effects and conditioned taste aversion following injections of vehicle or clozapine-N-oxide (CNO, the hM4Di agonist). RESULTS: CNO selectively blocked SS-PIT in the hM4Di-expressing group, but not controls, without altering expression of Pavlovian outcome devaluation or sensory-specific taste aversion in either group. Unexpectedly, CNO disrupted general PIT in both groups. CONCLUSIONS: CamKII BLA neurons mediate the expression of SS-PIT by enabling Pavlovian stimuli to trigger recall of the correct action-outcome associations rather than by mediating recall of the sensory-specific properties of the stimulus-outcome association. Separately, our data demonstrate that CNO alone is sufficient to disrupt affective, but not sensory-specific processes, an effect that was not due to generalized motor disruption. This non-specific effect on general PIT may be related to CNO-induced shifts in internal state. Together, these data identify BLA CamKII neurons as critical for the expression of SS-PIT and reveal important considerations for using CNO to study general affective motivation.

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Using a human Pavlovian-to-instrumental transfer (PIT) task, Alarcón and Bonardi showed that the selective elevation of instrumental responding produced by excitatory transfer cues was reduced when these cues were presented with a conditioned inhibitor (CI), relative to a control cue that was simply preexposed. However, previous research has shown that preexposed cues might also acquire inhibitor-like properties. This study aimed to contrast the inhibitory properties of CIs and preexposed cues, using novel stimuli as controls, in summation and PIT tests. Participants were trained to perform two actions, each reinforced with a distinct outcome (O1 or O2). Two images were trained as CIs, each signalling the absence of one of the outcomes, by presenting them with a cue that was otherwise followed by that outcome (e.g., A→O1, AI→no O1). In contrast, the preexposed cues were simply presented in the absence of the outcomes. In the summation test, participants rated the likelihood of the outcomes in the presence of two independently trained excitatory cues, each presented with a CI, a preexposed cue, or a novel stimulus. Similarly, in the PIT test, participants performed both actions in the presence and absence of these compounds. In the summation test, the CIs and the preexposed cues reduced participants' expectations of the outcomes more than the novel stimuli. However, in the PIT test, only the CIs reduced the selective elevation of responding produced by the transfer cues. These results might reflect distinct properties of stimuli trained as CIs and those simply preexposed.

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