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

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.

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

“…Discrete aversive stimuli evoke pauses in the firing rate of a clear majority of dopamine neurons (Cohen et al, 2012;Matsumoto and Hikosaka, 2009;Mirenowicz and Schultz, 1996) and suppress phasic dopamine release in the NAc (Badrinarayan et al, 2012;Oleson et al, 2012;Roitman et al, 2008;Wheeler et al, 2011; but also see Anstrom et al, 2009;Brischoux et al, 2009;Budygin et al, 2012;Park et al, 2015 for reported increases in phasic dopamine activity to aversive stimuli under some conditions). However, while discrete stimuli are commonly used to study phasic dopamine responses, the time domain of aversive stimuli can range from discrete to prolonged.…”

Evaluating long-term consequences of adolescent antipsychotic exposure

“…In addition, it is still unknown which major brain region is responsible for sensitized responses in the CAR. The NAc has been reported to play a central role in the maintenance of avoidance response (McCullough et al 1993;Oleson et al 2012). Intra-NAc injection of APD has also been reported to induce suppression of avoidance in a similar manner to systemic injection of APD (Wadenberg et al 1990b).…”

“…In adult APD treatment, alterations in DA system may be responsible for sensitized CAR suppression response. Two lines of evidence supporting this theory are: (1) DA neurotransmission in the striatum (Darvas et al 2011) and the NAc (McCullough et al 1993;Oleson et al 2012) plays an important role in the maintenance of CAR and (2) local injection of sulpiride, a D2 antagonist, into the NAc induces suppression of CAR (Wadenberg et al 1990b). Li and colleagues have also suggested that, in adult APD treatment, abnormal D2 receptor function may underlie sensitization-like CAR response.…”

“…I also wanted to examine whether short-term increases in striatal dopamine metabolites in risperidonetreated adolescents (Chapter 4) persisted after a lengthy drug-free interval. Mesolimbic dopaminergic system plays a major role in acquisition of the CAR (Fantin and Bottecchia 1984;Koob et al 1984;Oleson et al 2012;Ramirez et al 2015;Shumake et al 2010). This mesolimbic dopaminergic activity, in the NAc in particular, is thought to modulate motivational circuits and provide incentive value to neutral stimuli such as white noise or tone (CS) (Oleson and Cheer 2013).…”

“…Successful acquisition of the CAR has been related to neural activity in multiple brain regions such as the NAc (Oleson et al 2012), the VTA (Shumake et al 2010), the PFC (Stark et al 1999) and the amygdala (Choi et al 2010a;Darvas et al 2011;Lázaro-Muñoz et al 2010), the striatum (Darvas et al 2011;Dombrowski et al 2013). Connections between the NAc and the amygdala (Ramirez et al 2015) or between the PFC and the amygdala (Moscarello and LeDoux 2013) are also important for CAR acquisition.…”