Current Opinion in Behavioral Sciences

Understanding the neural mechanisms of risky decision-making is critical to developing appropriate treatments for psychiatric disorders, problem gambling, and addiction to drugs of abuse. Probing neurobiological mechanisms requires the use of nonhuman animal models (particularly rhesus macaques, rats, and mice). However, there is considerable variation across species in risk preferences. Nevertheless, there are shared core features of risky decision-making present across species. As demonstrated with a wide variety of behavioral paradigms, modulators of risk preference observed in humans are readily replicated in model species...

In major depressive disorder, women exhibit higher lifetime prevalence and different antidepressant response rates than men, which illustrates the importance of examining individual differences in the pathophysiology of depression and therapeutic response. In recent years, the consideration of sex in related preclinical research has thus gained interest-particularly in light of novel evidence for rapid-acting antidepressants. Notably, the literature recently revealed a higher sensitivity of females to the antidepressant effects of the N-methyl-D-aspartate receptor antagonist ketamine, in both baseline and preclinical conditions...

Adverse early-life experiences, including various forms of early-life stress, have consistently been linked with vulnerability to cognitive and emotional disorders later in life. Understanding the mechanisms underlying the enduring consequences of early-life stress is an active area of research, because this knowledge is critical for developing potential interventions. Animal models of early-life stress typically rely on manipulating maternal/parental presence and care, because these are the major source of early-life experiences in humans...

Young infant rat pups learn to approach cues associated with pain rather than learning amygdala-dependent fear. This approach response is considered caregiver-seeking and ecologically relevant within the context of attachment. With maturation, increases in the stress hormone corticosterone permit amygdala-dependent fear, which is crucial for survival during independent living. During the developmental transition from attachment to fear learning, maternal presence suppresses corticosterone elevation to block amygdala-dependent fear learning and re-engage the attachment circuitry...

A wide range of stressful experiences can influence human decision making in complex ways beyond the simple predictions of a fight-or-flight model. Recent advances may provide insight into this complicated interaction, potentially in directions that could result in translational applications. Early research suggests that stress exposure influences basic neural circuits involved in reward processing and learning, while also biasing decisions towards habit and modulating our propensity to engage in risk-taking...

Psychiatric diseases, notably major depression, are associated with imbalance of excitatory and inhibitory neurotransmission within the prefrontal cortex (PFC) and related limbic brain circuitry. In many cases these illnesses are precipitated or exacerbated by chronic stress, which also alters excitatory and inhibitory neurotransmitter systems. Notably, exposure to repeated uncontrollable stress causes persistent changes in the synaptic integrity and function of the principal glutamatergic excitatory neurons in the PFC, characterized by neuronal atrophy and loss of synaptic connections...

Many reports show that repeated cocaine administration increases dendritic spine density in medium spiny neurons of the nucleus accumbens, but there is less agreement regarding the persistence of these changes. In this review we examine these discrepancies by systematically categorizing papers that measured cocaine-induced changes in accumbal spine density. We compare published reports based on withdrawal time, short versus long duration of cocaine administration, environmental pairing with cocaine, and core/shell subregion specificity...

Fundamental to cognitive models of addiction is the gradual strengthening of automatic, urge-related responding that develops in tandem with the diminution of self-control-related processes aimed at inhibiting impulses. Recent conceptualizations of addiction also include a third set of cognitive processes related to self-awareness and superordinate regulation of self-control and other higher brain function. This review describes new human research evidence and theoretical developments related to the multicausal strengthening of urge-related responding and failure of self-control in addiction, and the etiology of disrupted self-awareness and rational decision-making associated with continued substance use...

The transition from moderate to compulsive alcohol drinking is driven by increasingly dysfunctional reward and stress systems. We review behavioral and pharmacological studies of alcohol self-administration in rats that were mainly conducted within the framework of the alcohol vapor model of dependence. We discuss neurotransmitter systems that are implicated in alcohol drinking, with a focus on contrasting those neurotransmitter systems that drive behavior in the dependent vs. nondependent states. We hypothesize that the identification of systems that become increasingly dysfunctional in alcohol dependence will reveal possible targets for successful interventions to reduce the motivation that drives compulsive alcohol drinking...

Chronic pain is a disease that encompasses both sensory and emotional elements. Opioids are highly effective analgesics because they target both of these elements, by inhibiting pain pathways and alleviating negative affect (including depression) by engaging reward or hedonic pathways. Unfortunately, chronic opioid use is limited by the development of unwanted side effects, such as tolerance, hyperalgesia, and abuse liability. Thus, the challenge of providing effective pain treatment while minimizing these unwanted side effects is an ongoing issue with significant clinical and societal impact...

Adolescence is a period of vulnerability for developing substance use disorder. Recent neuropsychological and neuroimaging studies have elucidated underlying neural vulnerabilities that contribute to initiation of substance use during adolescence. Findings suggest poorer performance on tasks of inhibition and working memory, smaller brain volumes in reward and cognitive control regions, less brain activation during executive functioning tasks, and heightened reward responsivity are predictive of youth initiating substance use during adolescence...

The prefrontal cortex (PFC) represents and executes the highest forms of goal-directed behavior, and has thereby attained a central neuroanatomical position in most pathophysiological conceptualizations of motivational disorders, including alcohol use disorder (AUD). Excessive, intermittent exposure to alcohol produces an allostatic dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis along with heightened forebrain glucocorticoid signaling that can damage PFC architecture and function. Negative affective states intimately associated with the transition to alcohol dependence result not only from a dysregulated HPA axis, but also from the inability of a damaged PFC to regulate subcortical stress and reinforcement centers, including the ventral striatum and amygdala...

Psychostimulant addiction is an important, relapsing condition for which there is no effective pharmacological treatment. Countering this problem requires an understanding of the specific risk factors that predispose individuals to initial misuse of these drugs. Healthy individuals display marked individual differences in emotional, behavioral and brain responses to low and moderate doses of stimulant drugs. These between-person differences have been most often studied using personality measures of sensation seeking...

The simultaneous and/or concurrent use of licit and illicit substances (polysubstance use, PSU) is most common today. Structural magnetic resonance imaging (MRI) has been applied extensively to study individuals ostensibly using a single substance. These studies have produced a picture of regional gray matter and white matter alterations with each substance or class of substances. Very few studies measured regional brain morphometry in today's polysubstance users. This limited data suggest morphometric alterations with PSU that are not simply additive but often different from those of monosubstance users...

Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality...

Cannabis use affects cortico-striatal networks that are essential for producing movement. In this review, we summarize the literature on motor system dysfunction in cannabis users and provide a rationale for why motor learning should be considered an important area in cannabis research. A majority of studies have addressed cognitive impairments in cannabis users and some have focused on driving performance, motor impulsivity, and motor inhibition. Our review of the literature has found that cannabis use is associated with motor performance impairments; however, there is a gap in the literature regarding impairments in motor learning...

Recent experiments suggest that subsecond dopamine delivery to human striatum encodes a combination of reward prediction errors and counterfactual errors thus composing the actual with the possible into one neurochemical signal. Here, we present a model where the counterfactual part of these striatal dopamine fluctuations originates in another valuation system that shadows the dopamine system by acting as its near-antipode in terms of spike-rate encoding yet co-releases dopamine alongside its own native neurotransmitter...

Understanding the neural basis of human honesty and deception has enormous potential scientific and practical value. However, past approaches, largely developed out of studies with forensic applications in mind, are increasingly recognized as having serious methodological and conceptual shortcomings. Here we propose to address these challenges by drawing on so-called signaling games widely used in game theory and ethology to study behavioral and evolutionary consequences of information transmission and distortion...

Generalizing knowledge from experimental data requires constructing theories capable of explaining observations and extending beyond them. Computational modeling offers formal quantitative methods for generating and testing theories of cognition and neural processing. These techniques can be used to extract general principles from specific experimental measurements, but introduce dangers inherent to theory: model-based analyses are conditioned on a set of fixed assumptions that impact the interpretations of experimental data...

To many, the poster child for David Marr's famous three levels of scientific inquiry is reinforcement learning-a computational theory of reward optimization, which readily prescribes algorithmic solutions that evidence striking resemblance to signals found in the brain, suggesting a straightforward neural implementation. Here we review questions that remain open at each level of analysis, concluding that the path forward to their resolution calls for inspiration across levels, rather than a focus on mutual constraints...