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Acute stress has various effects on cognition, executive function and certain forms of cost/benefit decision making. Recent studies in rodents indicate that acute stress differentially alters reward-related decisions involving particular types of costs and slows choice latencies. Yet, how stress alters decisions where rewards are linked to punishment is less clear. We examined how 1 h restraint stress, followed by behavioral testing 10 min later altered action-selection on two tasks involving reward-seeking under threat of punishment in well-trained male and female rats. One study used a risky decision-making task involving choice between a small/safe reward and a large/risky one that could coincide with shock, delivered with a probability that increased over blocks of trials. Stress increased risk aversion and punishment sensitivity, reducing preference for the larger/risky reward, while increasing decision latencies and trial omissions in both sexes, when rats were teste. A second study used a “behavioral control” task, requiring inhibition of approach towards a readily available reward associated with punishment. Here, food pellets were delivered over discrete trials, half of which coincided with a 12 s audiovisual cue, signalling that reward retrieval prior to cue termination would deliver shock. Stress exerted sex- and timing-dependent effects on inhibitory control. Males became more impulsive and received more shocks on the stress test, whereas females were unaffected on the stress test, and were actually less impulsive when tested 24 h later. None of the effects of restraint stress were recapitulated by systemic treatment with physiological doses of corticosterone. These findings suggest acute stress induces qualitatively distinct and sometimes sex-dependent effects on punished reward-seeking that are critically dependent on whether animals must either choose between different actions or withhold them to obtain rewards and avoid punishment.

Abstract Daily, individuals select actions based on cost-benefit to allocate resources into goal-directed actions. Different brain regions coordinate this complex decision, including the nucleus accumbens (NAc), anterior cingulate cortex (ACC), and ventral tegmental area (VTA). In utero exposure to synthetic glucocorticoids (iuGC), such as dexamethasone, triggers prominent motivation deficits but the impact of this exposure in the ACC-NAc and/or ACC-VTA circuits is unknown. Here, we show that iuGC exposure causes decreased motivation for natural rewards (food) and impaired effort-based decision-making. Importantly, reduced neuronal activation (number of c-fos+ neurons) was observed in the NAc core and ACC of iuGC rats in comparison to CTR rats after performing the effort-based decision-making task. In addition, iuGC treatment led to increased NAc and ACC basal neuronal activity. Electrophysiological recordings during optogenetic modulation of ACC terminals in the NAc revealed that the ACC-NAc circuit is dysfunctional in iuGC animals. These data suggest that iuGC animals present motivational and effort-based decision-making deficits that can be associated with the observed ACC-NAc dysfunction.

LTP and LTD are involved in shaping hippocampal place field representations. Here, the authors show that de novo pathway-specific hippocampal LTD changes dynamics and stability of newly formed place fields, regulating acquisition and maintenance of novel spatial information in adult rats.

Multiple lines of evidence indicate that androgens, such as testosterone, modulate the mesocorticolimbic system and executive function. This review integrates neuroanatomical, molecular biological, neurochemical, and behavioral studies to highlight how endogenous and exogenous androgens alter behaviors, such as behavioral flexibility, decision making, and risk taking. First, we briefly review the neuroanatomy of the mesocorticolimbic system, which mediates executive function, with a focus on the ventral tegmental area (VTA), nucleus accumbens (NAc), medial prefrontal cortex (mPFC), and orbitofrontal cortex (OFC). Second, we present evidence that androgen receptors (AR) and other steroid receptors are expressed in the mesocorticolimbic system. Using sensitive immunohistochemistry and quantitative polymerase chain reaction (qPCR) techniques, ARs are detected in the VTA, NAc, mPFC, and OFC. Third, we describe recent evidence for local androgens (“neuroandrogens”) in the mesocorticolimbic system. Steroidogenic enzymes are expressed in mesocorticolimbic regions. Furthermore, following long-term gonadectomy, testosterone is nondetectable in the blood but detectable in the mesocorticolimbic system, using liquid chromatography tandem mass spectrometry. However, the physiological relevance of neuroandrogens remains unknown. Fourth, we review how anabolic-androgenic steroids (AAS) influence the mesocorticolimbic system. Fifth, we describe how androgens modulate the neurochemistry and structure of the mesocorticolimbic system, particularly with regard to dopaminergic signaling. Finally, we discuss evidence that androgens influence executive functions, including the effects of androgen deprivation therapy and AAS. Taken together, the evidence indicates that androgens are critical modulators of executive function. Similar to dopamine signaling, there might be optimal levels of androgen signaling within the mesocorticolimbic system for executive functioning. Future studies should examine the regulation and functions of neurosteroids in the mesocorticolimbic system, as well as the potential deleterious and enduring effects of AAS use.

Studies on prefrontal cortex (PFC) dopamine (DA) function have revealed its essential role in mediating a variety of cognitive and executive functions. A general principle that has emerged (primarily from studies on working memory) is that PFC DA, acting on D1 receptors, regulates cognition in accordance to an inverted-U shaped function, so that too little or too much activity has detrimental effects on performance. However, contemporary studies have indicated that the receptor mechanisms through which mesocortical DA regulates different aspects of behavioral flexibility can vary considerably across different DA receptors and cognitive operations. This article will review psychopharmacological and neurochemical data comparing and contrasting the cognitive effects of antagonism and stimulation of different DA receptors in the medial PFC. Thus, set-shifting is dependent on a co-operative interaction between PFC D1 and D2 receptors, yet, supranormal stimulation of these receptors does not appear to have detrimental effects on this function. On the other hand, modification of cost/benefit decision biases in situations involving reward uncertainty is regulated in complex and sometimes opposing ways by PFC D1 versus D2 receptors. When viewed collectively, these findings suggest that the inverted-U shaped dose-response curve underlying D1 receptor modulation of working memory is not a one-size-fits-all function. Rather, it appears that mesocortical DA exerts its effects via a family of functions, wherein reduced or excessive DA activity can have a variety of effects across different cognitive domains.