Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Cheer, Joseph F.; Heien, Michael L.; Garris, Paul A.; Carelli, Regina M.; Wightman, R. Mark

doi:10.1073/pnas.0509607102

Cited by 122 publications

(138 citation statements)

References 55 publications

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“…Future studies will be required to evaluate dopaminergic activity in the NAc core during similar behaviors, as discussed in prior work (18). Indeed, using a similar protocol, we previously reported stimulus evoked dopamine changes in the NAc core, but, over a limited set of trials, these were unaccompanied by cueevoked dopamine signals (46). Taken together, the data presented here suggest a complex role of NAc dopamine in ICSS.…”

Section: Discussionsupporting

confidence: 61%

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

Owesson-White

Cheer²,

Beyene³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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118

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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...

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Section: Discussionsupporting

confidence: 61%

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

Owesson-White

Cheer²,

Beyene³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

118

167

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“…Although predicted by animal results indicating that dopamine is closely associated with reward processing (2,3,(14)(15)(16)(17)(18), such an association has not previously been shown directly in humans. Moreover, our multimodal imaging approach offers key insights into findings with fMRI, a technique that cannot by itself directly relate BOLD signal changes observed in the reward system with dopaminergic activity, a challenge met by our concurrent measurements of midbrain dopamine synthesis with FDOPA PET.…”

Section: Discussionmentioning

confidence: 78%

Age-related changes in midbrain dopaminergic regulation of the human reward system

Dreher

Meyer‐Lindenberg

Kohn

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

200

153

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The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharmacological and clinical studies also supports such an association, there has been no direct demonstration of a link between midbrain dopamine and rewardrelated neural response. Moreover, there are no in vivo data for alterations in this relationship in older humans. Here, by using 6-[ 18 F]FluoroDOPA (FDOPA) positron emission tomography (PET) and event-related 3T functional magnetic resonance imaging (fMRI) in the same subjects, we directly demonstrate a link between midbrain dopamine synthesis and reward-related prefrontal activity in humans, show that healthy aging induces functional alterations in the reward system, and identify an age-related change in the direction of the relationship (from a positive to a negative correlation) between midbrain dopamine synthesis and prefrontal activity. These results indicate an age-dependent dopaminergic tuning mechanism for cortical reward processing and provide system-level information about alteration of a key neural circuit in healthy aging. Taken together, our findings provide an important characterization of the interactions between midbrain dopamine function and the reward system in healthy young humans and older subjects, and identify the changes in this regulatory circuit that accompany aging.aging ͉ dopamine ͉ fMRI ͉ PET ͉ reinforcement S uccessful aging has become one of the most crucial public health challenges of our time. Achieving an understanding of age-related changes in the neurobiology of key brain circuits, such as the reward system, is an integral part of rising to this challenge. Detecting, predicting, and responding to reward information are fundamental capabilities of simple life forms that have evolved in humans into complex behavioral patterns, such as learning, motivation, and appetitive and hedonic activities, which remain essential as we age. A substantial body of data in animals indicates that dopamine is closely associated with reward processing (1-3), and that midbrain dopamine neurons send reward-related signals to postsynaptic sites, particularly the prefrontal cortex. In humans, although indirect evidence from pharmacological (4, 5) and clinical (6-8) studies also suggests a fundamental role of dopamine in reward processing, there has been no direct demonstration of a link between midbrain dopamine and reward-related neural response. Moreover, although the dopamine system is known to be particularly vulnerable to aging (9, 10), there has been no search for alterations in this predicted relationship in older humans. Here, by using 6-[ 18 F]fluoroDOPA ...

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“…For example, ICSS promotes DA release in nucleus accumbens; it is enhanced by drugs that themselves increase extracellular DA levels in nucleus accumbens, and it is blocked by drugs that deplete DA or block DA receptors (Stellar and Stellar, 1985;Phillips et al, 1989;Fiorino et al, 1993;Wise, 1998;You et al, 2001;Cheer et al, 2005) [but see (Miliaressis et al, 1991;Kruk et al, 1998)]. Mesolimbic DA neurons constitute one subset of neurons that project through the MFB Veening et al, 1982), and optogenetic studies suggest that direct activation of these neurons is sufficient to maintain ICSS (You et al, 2001;Kim et al, 2012).…”

Section: A Definition Discovery and Neural Substratesmentioning

confidence: 99%

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

2014

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Simultaneous dopamine and single-unit recordings reveal accumbens GABAergic responses: Implications for intracranial self-stimulation

Cited by 122 publications

References 55 publications

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

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

Age-related changes in midbrain dopaminergic regulation of the human reward system

Intracranial Self-Stimulation to Evaluate Abuse Potential of Drugs

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