Cocaine Cues Drive Opposing Context-Dependent Shifts in Reward Processing and Emotional State

Abstract

Background-Prominent neurobiological theories of addiction posit a central role for aberrant mesolimbic dopamine release, but disagree as to whether repeated drug experience blunts or enhances this system. While drug withdrawal diminishes dopamine release, drug sensitization augments mesolimbic function, and both processes have been linked to drug-seeking. One possibility is that the dopamine system can rapidly switch from dampened to enhanced release depending upon the specific drug-predictive environment. To test this, we examined dopamine release when cues signaled delayed cocaine delivery versus imminent cocaine self-administration.

The role of dopamine in the pursuit of nutritional value

“…In general, these substances are readily consumed by mice and rats and elicit appetitive orofacial reactions if infused intraorally, suggesting a positive hedonic evaluation [28,29]. Moreover, mice and rats show increased dopamine efflux and dopamine release in response to free consumption or intraoral delivery of nonnutritive sweeteners [22,30,31]. However, the extent to which these non-nutritive compounds participate in reinforcement/conditioning and how they interact with dopamine signalling during these processes is less clear.…”

κ-Opioid Receptors within the Nucleus Accumbens Shell Mediate Pair Bond Maintenance

“…For example, both unconditioned rewarding and aversive stimuli increase DA in the NAc shell (Kalivas and Duffy, 1995;Ikemoto, 2007), and this increase is associated with aspects of both approach and avoidance behaviors (Ikemoto and Panksepp, 1999;Di Chiara and Bassareo, 2007;Oleson et al, 2012). Thus, while aversive chemical stimuli have been shown to decrease DA transmission in the NAc shell (Roitman et al, 2008;Wheeler et al, 2011), there are many conditions in which DA release in the NAc shell is critical for the attribution of motivational salience to unconditioned salient stimuli regardless of the valence (Kelley and Berridge, 2002). While recent data have demonstrated that different subsets of DA containing neurons within the VTA are activated by rewarding versus aversive stimuli (Brischoux et al, 2009;Matsumoto and Hikosaka, 2009;Bromberg-Martin et al, 2010;Lammel et al, 2011), it has yet to be determined how this may be associated with social incentives.…”

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

“…The present data strengthen a dopamine-suppressive action of aversive stimuli that is consistent with investigations of discrete stimuli in awake and behaving subjects. These studies utilize electrophysiological and electrochemical recordings to demonstrate pauses in dopamine neuron firing (Cohen et al, 2012;Matsumoto and Hikosaka, 2009;Mirenowicz and Schultz, 1996) and dopamine release (Badrinarayan et al, 2012;Roitman et al, 2008;Wheeler et al, 2011) in the NAc following discrete aversive stimuli. Our work extends these findings to include a dopamine-suppressive action of an agent, LiCl, which produces a long-lasting aversive state Tomasiewicz et al, 2006).…”

“…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.…”