Subsecond Dopamine Release in the Nucleus Accumbens Predicts Conditioned Punishment and Its Successful Avoidance

Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 10/2012; 32(42):14804-8. DOI: 10.1523/JNEUROSCI.3087-12.2012
Source: PubMed

ABSTRACT The mesolimbic dopamine system is believed to be a pathway that processes rewarding information. While previous studies have also implicated a general role for dopamine in punishment and its avoidance, the precise nature of subsecond dopamine release during these phenomena remains unknown. Here, we used fast-scan cyclic voltammetry to investigate whether subsecond dopamine release events in the nucleus accumbens encode cues predicting the avoidance of punishment during behavior maintained in a signaled footshock avoidance procedure. In this task, rats could initiate an avoidance response by pressing a lever within a warning period, preventing footshock. Alternatively, once footshocks commenced, animals could initiate an escape response by pressing the lever, terminating footshock. This design allowed us to assess subsecond dopamine release events during the presentation of a warning signal, safety periods, and two distinct behavioral responses. We found that release consistently increased upon presentation of the warning signal in a manner that reliably predicted successful punishment avoidance. We also observed subsecond dopamine release during the safety period, as occurs following the receipt of reward. Conversely, we observed a decrease in release at the warning signal during escape responses. Because of this finding, we next assessed dopamine release in a conditioned fear model. As seen during escape responses, we observed a time-locked decrease in dopamine release upon presentation of a cue conditioned to inescapable footshock. Together, these data show that subsecond fluctuations in mesolimbic dopamine release predict when rats will successfully avoid punishment and differentially encode cues related to aversive outcomes.

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Available from: Erik Oleson, Jul 19, 2015
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    • "Consistent with this theory, it has been recently demonstrated that subsecond dopamine release, which supplies such a prediction error signal, is elevated when rats successfully avoid being shocked (Oleson et al., 2012). All of this suggests a very important role for the NAc during avoidance, thus it seems unlikely that NAc signals would impede performance. "
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    ABSTRACT: The majority of work examining nucleus accumbens core (NAc) has focused on functions pertaining to behaviors guided by appetitive outcomes. These studies have pointed to NAc as being critical for motivating behavior toward desirable outcomes. For example, we have recently shown that lesions of NAc impaired performance on a reward-guided decision-making task that required rats to choose between differently valued rewards. Unfortunately, much less is known about the role that NAc plays in motivating behavior when aversive outcomes are predicted. To address this issue we asked if NAc lesions impact performance on a two-way active avoidance task in which rats must learn to shuttle back and forth in a behavioral training box in order to avoid a footshock predicted by an auditory tone. Although bilateral NAc lesions initially impaired reward-guided decision-making, we found that the same lesions improved acquisition and retention of two-way active avoidance.
    Neuroscience 11/2013; DOI:10.1016/j.neuroscience.2013.11.028 · 3.33 Impact Factor
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    • "Fear cues have been shown to decrease DA transmission in the NAc core, but increase transmission in the shell [41]. Dopamine release in the NAc also appears to assist in encoding cues that predict punishment avoidance [42]. These data suggest a role between fear and DA transmission and suggest that there may also be a role of accumbal DA in anxiety-like behavior. "
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    ABSTRACT: The majority of smokers start smoking in adolescence, beginning a potentially lifelong struggle with nicotine use and abuse. In rodent models of the effects of nicotine, the drug has been shown to elicit both locomotor and anxiety-like behavioral effects. Research suggests that these behavioral effects may be due in part to dopamine (DA) receptors D1 and D2 in the mesolimbic system, specifically the nucleus accumbens (NAc). We examined early adolescent (P28), late adolescent (P45), and adult (P80) male Long-Evans rats in the elevated plus maze (EPM) under normal conditions and the open field (OF) post-nicotine in order to test locomotor and anxiety-like behavior. These behavioral findings were then correlated with expression of DA D1 and D2 mRNA levels as determined via in situ hybridization. Nicotine-induced locomotor behavior was found to be significantly different between age groups. After a single injection of nicotine, early adolescents exhibited increases in locomotor behavior, whereas both late adolescents and adults responded with decreases in locomotor behavior. In addition, it was found that among, early adolescents, open arm and center time in the EPM were negatively correlated with D2 mRNA expression. In contrast, among adults, distance traveled in the center and center time in the OF were negatively correlated with D2 mRNA expression. This study suggests that DA D2 receptors play a role in anxiety-like behavior and that the relationship between observed anxiety-like behaviors and D2 receptor expression changes through the lifespan.
    Behavioural brain research 11/2013; 260. DOI:10.1016/j.bbr.2013.11.007 · 3.39 Impact Factor
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    • "We recently demonstrated that subsecond dopamine release events encode conditioned cues during behaviors driven by negative reinforcement, and that these subsecond dopamine release events are critically modulated by endocannabinoid signaling (Oleson et al., 2012a, 2012b). Understanding the neural mechanisms underlying these dopaminergic changes may offer novel insights into drug addiction, as avoidance from drug withdrawal is thought to promote compulsive drug seeking. "
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    ABSTRACT: Environmental and interoceptive cues are theorized to serve as 'signals' that motivate drug seeking, effects that may be augmented in the withdrawn state. Phasic dopamine release events are observed in the nucleus accumbens in response to such motivational salient stimuli and are thought to be necessary for drug-associated cues to trigger craving. We recently demonstrated how dopamine neurons encode stimuli conditioned to a negative event, as might occur during conditioned withdrawal, and stimuli predicting the avoidance of negative events, as might occur as an addict seeks out drugs to prevent withdrawal. In this review we first discuss how the subsecond dopamine release events might process conditioned withdrawal and drug seeking driven by negative reinforcement processes within the context of our dopamine data obtained during conditioned avoidance procedures. We next describe how the endocannabinoid system modulates phasic dopamine release events and how it might be harnessed to treat negative affective states in addiction. Specifically, we have demonstrated that endocannabinoids in the ventral tegmentum sculpt cue-induced accumbal surges in dopamine release and, therefore, may also be mobilized during drug withdrawal.
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