Impaired decision-making is a core problem in several psychiatric disorders including attention-deficit/hyperactivity disorder, schizophrenia, obsessive–compulsive disorder, mania, drug addiction, eating disorders, and substance abuse as well as in chronic pain. To ensure progress in the understanding of the neuropathophysiology of these disorders, animal models with good construct and predictive validity are indispensable. Many human studies aimed at measuring decision-making capacities use the Iowa gambling task (IGT), a task designed to model everyday life choices through a conflict between immediate gratification and long-term outcomes. Recently, new rodent models based on the same principle have been developed to investigate the neurobiological mechanisms underlying IGT-like decision-making on behavioral, neural, and pharmacological levels. The comparative strengths, as well as the similarities and differences between these paradigms are discussed. The contribution of these models to elucidate the neurobehavioral factors that lead to poor decision-making and to the development of better treatments for psychiatric illness is considered, along with important future directions and potential limitations.

Deficits in decision-making is a hallmark of several neuropsychiatric pathologies but is also observed in some healthy individuals that could be at risk to develop these pathologies. Poor decision-making can be revealed experimentally in humans using the Iowa gambling task, through the inability to select options that ensure long term gains over larger immediate gratification. We devised an analogous task in the rat, based on uncertainty and conflicting choices, the rat gambling task (RGT). It similarly reveals good and poor performers within a single session. Using this task, we investigated the role of three prefrontal cortical areas, the orbitofrontal, prelimbic, and cingulate cortices on decision-making, taking into account inter-individual variability in behavioral performances. Here, we show that these three distinct subregions are differentially engaged to solve the RGT. Cingulate cortex lesion mainly delayed good decision-making whereas prelimbic and orbitofrontal cortices induced different patterns of inadapted behaviors in the task, indicating varying degree of functional specialization of these three areas. Their contribution largely depended on the level of adaptability demonstrated by each individual to the constraint of the task. The inter-individual differences in the effect of prefrontal cortex area lesions on decision-making revealed in this study open new perspectives in the search for vulnerability markers to develop disorders related to executive dysfunctioning.

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The ability to discern temporally pertinent environmental events is essential for the generation of adaptive behavior in conventional tasks, and our overall survival. Cannabinoids are thought to disrupt temporally controlled behaviors by interfering with dedicated brain timing networks. Cannabinoids also increase dopamine release within the mesolimbic system, a neural pathway generally implicated in timing behavior. Timing can be assessed using fixed-interval (FI) schedules, which reinforce behavior on the basis of time. To date, it remains unknown how cannabinoids modulate dopamine release when responding under FI conditions, and for that matter, how subsecond dopamine release is related to time in these tasks. In the present study, we hypothesized that cannabinoids would accelerate timing behavior in an FI task while concurrently augmenting a temporally relevant pattern of dopamine release. To assess this possibility, we measured subsecond dopamine concentrations in the nucleus accumbens while mice responded for food under the influence of the cannabinoid agonist WIN 55 212-2 in an FI task. Our data reveal that accumbal dopamine concentrations decrease proportionally to interval duration-suggesting that dopamine encodes time in FI tasks. We further demonstrate that WIN 55 212-2 dose-dependently increases dopamine release and accelerates a temporal behavioral response pattern in a CB1 receptor-dependent manner-suggesting that cannabinoid receptor activation modifies timing behavior, in part, by augmenting time-engendered patterns of dopamine release. Additional investigation uncovered a specific role for endogenous cannabinoid tone in timing behavior, as elevations in 2-arachidonoylglycerol, but not anandamide, significantly accelerated the temporal response pattern in a manner akin to WIN 55 212-2.