Operant behavior during sessions of intravenous cocaine infusion is necessary and sufficient for phasic firing of single nucleus accumbens neurons

Peoples, Laura L.; Uzwiak, Anthony J.; Gee, Fred; West, Mark O.

doi:10.1016/s0006-8993(97)00299-0

Cited by 65 publications

(45 citation statements)

References 14 publications

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“…This biphasic pattern of activity could facilitate switching from appetitive to consummatory behaviors. Interestingly, one of the most prevalent firing patterns in the NAc of rats during cocaine self-administration is a longlasting inhibition that begins on cocaine delivery and slowly recovers before the animal begins to work for the next injection (Nicola and Deadwyler 2000;Peoples and West 1996;Peoples et al 1998). The time course of inhibition parallels that of cocaine metabolism and is dependent on dopamine (Nicola and Deadwyler 2000), and the same neurons tend to show excitations just before and during operant behavior (Nicola and Deadwyler 2000;Peoples and West 1996).…”

Section: Information Encoded By Sustained Receptacle Excitations and mentioning

confidence: 99%

“…For instance, receipt of cocaine during self-administration results in long-lasting inhibition of many NAc neurons (Nicola and Deadwyler 2000;Peoples and West 1996;Peoples et al 1998) as well as inhibitions or excitations on a shorter time scale (Carelli and Deadwyler 1994;Carelli et al 1993;Chang et al 1994Chang et al , 1996Peoples and West 1996;Peoples et al 1997;Uzwiak et al 1997). Selfadministration of other drugs, such as ethanol and heroin, is also associated with excitation and inhibition after each operant response (Chang et al 1998;Janak et al 1999;Lee et al 1999).…”

Section: Introductionmentioning

confidence: 99%

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Firing of Nucleus Accumbens Neurons During the Consummatory Phase of a Discriminative Stimulus Task Depends on Previous Reward Predictive Cues

Nicola

Yun

Wakabayashi

et al. 2004

Journal of Neurophysiology

112

102

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. Firing of nucleus accumbens neurons during the consummatory phase of a discriminative stimulus task depends on previous reward predictive cues . J Neurophysiol 91: 1866 -1882, 2004. First published November 26, 2003 10.1152/jn.00658.2003. The nucleus accumbens (NAc) plays an important role in both appetitive and consummatory behavior. To examine how NAc neurons encode information during reward consumption, we recorded the firing activity of rat NAc neurons during the performance of a discriminative stimulus task. In this task, the animal must make an operant response to an intermittently presented cue to obtain a sucrose reward delivered in a reward receptacle. Uncued entries to the receptacle were not rewarded. Both excitations and inhibitions during reward consumption were observed, but substantially more neurons were inhibited than excited. These excitations and inhibitions began when the animal entered the reward receptacle and ended when the animal exited the receptacle. Both excitations and inhibitions were much smaller or nonexistent when the animal made uncued entries into the reward receptacle. In one set of experiments, we randomly withheld the reward in some cued trials that would otherwise have been rewarded. Excitations and inhibitions were of similar magnitude whether or not the reward was delivered. This indicates that the sensory stimulus of reward does not drive these phasic responses; instead, the rewardassociated responses may be driven by the conditioned stimuli associated with reward, or they may encode information about consummatory motor activity. Another population of NAc neurons was excited on exit from the reward receptacle. Many of these excitations persisted for tens of seconds after the receptacle exit and showed a significant inverse correlation with the rate of uncued operant responding. These findings are consistent with a contribution of NAc neurons to both reward consummatory and reward seeking behavior.

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Section: Information Encoded By Sustained Receptacle Excitations and mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Firing of Nucleus Accumbens Neurons During the Consummatory Phase of a Discriminative Stimulus Task Depends on Previous Reward Predictive Cues

Nicola

Yun

Wakabayashi

et al. 2004

Journal of Neurophysiology

112

102

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“…Populations of these cells show patterned changes in firing that either occur within seconds of the reinforced response (immediately before or after a lever press for IV cocaine) or that persist for several minutes during the period between IV infusions (Carelli & Deadwyler, 1994Carelli, King, Hampson, & Deadwyler, 1993;Chang, Sawyer, Lee, & Woodward, 1994;Nicola & Deadwyler, 2000;Peoples, Uzwiak, Gee, & West, 1997;Peoples & West, 1996;Uzwiak, Guyette, West, & Peoples, 1997). The period immediately before the lever press for IV cocaine is likely related to drug-seeking behavior and a subset of NAcc neurons show increases or decreases in activity.…”

Section: Electrophysiology Of Cocaine Seekingmentioning

confidence: 99%

Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

Rebec¹,

Sun²

2005

Journal of the Experimental Analysis of Behavior

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The return to drug seeking, even after prolonged periods of abstinence, is a defining feature of cocaine addiction. The neural circuitry underlying relapse has been identified in neuropharmacological studies of experimental animals, typically rats, and supported in brain imaging studies of human addicts. Although the nucleus accumbens (NAcc), which has long been implicated in goal-directed behavior, plays a critical role in this circuit, the prefrontal cortex (PFC) appears to process the events that directly trigger relapse: exposure to acute stress, cues previously associated with the drug, and the drug itself. In this paper, we review animal models of relapse and what they have revealed about the mechanisms underlying the involvement of the NAcc and PFC in cocaine-seeking behavior. We also present electrophysiological data from PFC illustrating how the hedonic, motor, motivational, and reinforcing effects of cocaine can be analyzed at the neuronal level. Our preliminary findings suggest a role for PFC in processing information related to cocaine seeking but not the hedonic effects of the drug. Further use of this recording technology can help dissect the functions of PFC and other components of the neural circuitry underlying relapse.Key words: cocaine seeking, prefrontal cortex (PFC), nucleus accumbens (NAcc), drug selfadministration, reinstatement, single-unit, electrophysiology, rat _______________________________________________________________________________ Repeated use of amphetamine, cocaine, and related psychomotor stimulants can elicit longlasting changes in behavior. Evidence of this effect in human addicts is a high rate of relapse, which often occurs months or years after the last use. In fact, relapse prevention is perhaps the single biggest challenge to successful treatment of stimulant addiction. Reaching this goal requires an understanding of the neurobiological substrates of addictive behavior. Excellent progress has come from research on the brain circuits underlying the reinstatement of cocaine seeking in experimental animals, typically rats (for review, see . In this report, we describe the reinstatement model and what it has revealed about the role of prefrontal cortex (PFC) in relapse to cocaine seeking. Although most research on the brain substrates of reinstatement has focused on the nucleus accumbens (NAcc), which has long been linked to appetitive behavior and arousal (LeMoal, 1995), increasing evidence implicates the PFC as the final common pathway by which the stimuli that trigger reinstatement converge to drive behavior (Kalivas & Nakamura, 1999).At the neuronal level, however, relatively little information is available on how the PFC processes information related to relapse. A powerful tool that can be used to address this issue is extracellular, single-unit recording from awake, unrestrained animals. Not only is the neuronal circuitry intact and functioning normally in this preparation, but with chronically implanted micro-wires, neuronal activity can be recorded when animals a...

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“…This hypothesis is based on a number of previous observations. Numerous studies have shown that during cocaine selfadministration sessions, only a subset of accumbal neurons show changes in activity related to encoding aspects of the instrumental task (eg Carelli et al, 1993;Peoples et al, 1997Peoples et al, , 1998b. The majority of those neurons show either transient or tonic increases in firing during the period of drug exposure (referred to as Task-Activated neurons).…”

Section: Introductionmentioning

confidence: 99%

Accumbal Neurons that are Activated during Cocaine Self-Administration are Spared from Inhibitory Effects of Repeated Cocaine Self-Administration

Peoples

Kravitz

Lynch

et al. 2006

Neuropsychopharmacol

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Hypoactivity of the accumbens is induced by repeated cocaine exposure and is hypothesized to play a role in cocaine addiction. However, it is difficult to understand how a general hypoactivity of the accumbens, which facilitates multiple types of motivated behaviors, could contribute to the selective increase in drug-directed behavior that defines addiction. Electrophysiological recordings, made during sessions in which rats self-administer cocaine, show that most accumbal neurons that encode events related to drugdirected behavior achieve and maintain higher firing rates during the period of cocaine exposure (Task-Activated neurons) than do other accumbal neurons (Task-Non-Activated neurons). We have hypothesized that this difference in activity makes the neurons that facilitate drug-directed behavior less susceptible than other neurons to the chronic inhibitory effects of cocaine. A sparing of neurons that facilitate drug-directed behavior from chronic hypoactivity might lead to a relative increase in the transmission of neuronal signals that facilitate drug-directed behavior through accumbal circuits and thereby contribute to changes in behavior that characterize addiction (ie differential inhibition hypothesis). A prediction of the hypothesis is that neurons that are activated in relation to task events during cocaine self-administration sessions will show less of a decrease in firing across repeated self-administration sessions than will other neurons. To test this prediction, rats were exposed to 30 daily (6 h/day) cocaine self-administration sessions. Chronic extracellular recordings of single accumbal neurons were made during the second to third session and the 30th session. Between-session comparisons showed that decreases in firing were exhibited by Task-Non-Activated, but not by Task-Activated, neurons. During the day 30 session, the magnitude of the difference in firing rate between the two groups of neurons was positively related to the propensity of animals to seek and take cocaine. The findings of the present study are consistent with a basic prediction of the differential inhibition hypothesis and may be relevant to understanding cocaine addiction.

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Operant behavior during sessions of intravenous cocaine infusion is necessary and sufficient for phasic firing of single nucleus accumbens neurons

Cited by 65 publications

References 14 publications

Firing of Nucleus Accumbens Neurons During the Consummatory Phase of a Discriminative Stimulus Task Depends on Previous Reward Predictive Cues

Firing of Nucleus Accumbens Neurons During the Consummatory Phase of a Discriminative Stimulus Task Depends on Previous Reward Predictive Cues

Neuronal Substrates of Relapse to Cocaine-Seeking Behavior: Role of Prefrontal Cortex

Accumbal Neurons that are Activated during Cocaine Self-Administration are Spared from Inhibitory Effects of Repeated Cocaine Self-Administration

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