Dynamic changes in accumbens dopamine correlate with learning during intracranial self-stimulation

Abstract

Dopamine in the nucleus accumbens (NAc) is an important neurotransmitter for reward-seeking behaviors such as intracranial selfstimulation (ICSS), although its precise role remains unclear. Here, dynamic fluctuations in extracellular dopamine were measured during ICSS in the rat NAc shell with fast-scan cyclic voltammetry at carbon-fiber microelectrodes. Rats were trained to press a lever to deliver electrical stimulation to the substantia nigra (SNc)/ ventral tegmental area (VTA) after the random onset of a cue that predicted reward availability. Latency to respond after cue onset significantly declined across trials, indicative of learning. Dopamine release was evoked by the stimulation but also developed across trials in a time-locked fashion to the cue. Once established, the cue-evoked dopamine transients continued to grow in amplitude, although they were variable from trial to trial. The emergence of cue-evoked dopamine correlated with a decline in electrically evoked dopamine release. Extinction of ICSS resulted in a significant decline in goal-directed behavior coupled to a significant decrease in cue-evoked phasic dopamine across trials. carbon-fiber electrode ͉ cyclic voltammetry ͉ extinction ͉ nucleus accumbens shell ͉ reward I ntracranial self-stimulation (ICSS) was discovered in 1954 (1). In this paradigm, a rat depresses a lever to deliver an electric shock to electrodes implanted within the brain. Extensive mapping studies by Olds and Olds later showed that the neuroanatomical region supporting ICSS centered in the posterior MFB region of the lateral hypothalamus (2). This finding provoked considerable interest, because it identified a brain reward pathway that could be centrally activated without the need for sensory stimulation (3, 4). Although a role for several neurotransmitters has been implicated in ICSS, dopamine appears to play a primary role (5, 6), leading to the view that dopaminergic signaling is essential during goal-directed behaviors. Indeed, it was postulated that increased dopaminergic neurotransmission was necessary for the reinforcement of reward-related behavior (7).More recently, electrophysiological studies in primates have provided new insight into the role of dopaminergic neurons in reward processing (8). In response to unexpected rewards, dopamine neurons exhibit phasic firing. However, when an animal learns that a cue predicts reward, the burst of neuronal firing switches to the onset of the cue (9-12). Responses to the cue increase with repeated trials, and these paired responses of midbrain dopamine neurons follow the expectations of models of associative learning in which dopamine signaling is a reward-prediction error (12,13). Similar responses to conditioned stimuli that predict reward have also been observed for midbrain dopaminergic neurons in rats (14).A phasic increase in dopamine neuronal firing should lead to a dopamine concentration transient in terminal areas such as the nucleus accumbens (NAc). Indeed, using fast-scan cyclic voltammetry at carbon-fiber microe...

Amphetamine modulates brain signal variability and working memory in younger and older adults

“…In addition, in line with the contention that brain signal variability can index a healthy neural system (2), animal models indicate that trial-to-trial variability in DA release appears to increase, rather than decrease, with increasing task proficiency (20). From this work, it is plausible that DA may also affect in vivo brain signal variability and its cognitive correlates in humans.…”

“…DA is typically associated with various forms of learning (9,10,13,14,39), but data on how DA modulation interacts with practice remain sparse. Of the few available studies, Owesson-White et al (20) demonstrated that DA release increases linearly with reward-based lever press practice in rats. Accordingly, one mechanism to support our findings may be that, by allowing practice, we shifted participants along an inverted-U-shaped DA-performance curve (13) by increasing baseline DA release.…”

“…2), those exhibiting the greatest AMPH-related increases in SD BOLD indeed showed the greatest improvements in RT mean and RT SD . However, in this AMPH-placebo group, practice effects unavoidably worked against AMPH-related modulations; as practicerelated improvements are expressed at retest (placebo), any AMPHrelated effects could then be attenuated due to practice-related increases in DA release (20). Although practice effects are unlikely to confound AMPH effects completely (34), a four-cell study design (placebo/placebo, placebo/drug, drug/placebo, drug/drug) may be needed to separate within-subject practice from drug effects.…”

Reward Sensitization: Effects of Repeated Nicotine Exposure and Withdrawal in Mice

“…Interestingly, we also observed a decline in the latency to respond in the saline animals with extended training. This effect was observed previously and interpreted as a result of motor-learning (Owesson-White et al, 2008). Thus, it is possible that a motor-learning impairment might be implicated in the increased response latencies of nicotine-treated animals.…”

Cross-hemispheric dopamine projections have functional significance

“…Dopamine is released on a subsecond timescale during unexpected reward (1,2), and becomes time-locked to cues that predict reward (3)(4)(5)(6)(7). Dopamine transients in the nucleus accumbens (NAc) occur as a result of cell firing in the ventral tegmental area (VTA) (8,9), and in rats reach concentrations of 50-200 nM before returning to baseline (10,11).…”