Previous Cocaine Exposure Makes Rats Hypersensitive to Both Delay and Reward Magnitude

Roesch, Matthew R.; Takahashi, Yuji K.; Gugsa, Nishan; Bissonette, Gregory B.; Schoenbaum, Geoffrey

doi:10.1523/jneurosci.4080-06.2007

Cited by 109 publications

(114 citation statements)

References 41 publications

(56 reference statements)

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“…There is accumulating evidence that repeated passive exposure to psychostimulants leads to deficits in tasks that depend on intact prefrontal cortex function (Fletcher et al, 2005(Fletcher et al, , 2007Roesch et al, 2007;Schoenbaum et al, 2004;Schoenbaum and Setlow, 2005). Moreover, withdrawal from repeated passive cocaine or amphetamine treatments also decreases firing rate and bursting activity of dmPFC neurons (Nogueira et al, 2006;Homayoun and Moghaddam, 2007) and abolishes dopamine D 2 receptor-mediated regulation of dmPFC excitability (Nogueira et al, 2006) and membrane bistability of dmPFC neurons (Trantham et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

George

Mandyam

Wee

et al. 2007

Neuropsychopharmacol

152

127

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Humans with drug addiction exhibit compulsive drug-seeking associated with impairment of prefrontal cortex cognitive function. Whether prefrontal cortex dysfunction is a consequence of chronic drug exposure, or mediates the transition from drug use to drug dependence, is unknown. The current study investigates whether a history of escalated vs controlled cocaine intake is associated with specific working memory impairments, and long-lasting alterations of the dorsomedial prefrontal cortex and orbitofrontal cortex in rats. Working memory was assessed in rats with a history of extended (6 h per session) or limited (1 h per session) access to cocaine (0.5 mg/kg per injection), 3-17 days after the last self-administration session, using a delayed nonmatching-to-sample task. The density of neurons, oligodendrocytes, and astrocytes was quantified in the dorsomedial prefrontal cortex and orbitofrontal prefrontal cortex 2 months after the last self-administration session. Working memory impairments were observed after a history of chronic and escalated cocaine intake, but not after repeated limited access to cocaine. Moreover, working memory impairments were correlated with a decreased density of neurons and oligodendrocytes but not astrocytes in the dorsomedial prefrontal cortex, and with a decreased density of oligodendrocytes in the orbitofrontal cortex. Considering the role of the prefrontal cortex in goal-directed behavior, the prefrontal cortex dysfunctions observed here may exacerbate the loss of control associated with increased drug use and facilitate the progression to drug addiction.

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Section: Discussionmentioning

confidence: 99%

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

George

Mandyam

Wee

et al. 2007

Neuropsychopharmacol

152

127

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“…To our knowledge, no published studies have described the effects of chronic AMPH exposure on delay-discounting behavior in an animal model, but several have examined other psychostimulants (Richards et al 1999;Paine et al 2003;Roesch et al 2007;Simon et al 2007;Winstanley et al 2007). While most of these reports suggested that repeated psychostimulant exposure increases impulsive decisions, the most extensive study to date (Winstanley et al 2007) reported no baseline impairments in impulsive choice in rats exposed repeatedly to cocaine (15 mg/kg, i.p., for 21 days).…”

Section: Discussionmentioning

confidence: 99%

“…Although increased impulsivity is considered to be characteristic of individuals who abuse drugs (e.g., Jentsch and Taylor 1999;Coffey et al 2003;Kirby and Petry 2004;Heil et al 2006;Hoffman et al 2006;Verdejo-Garcia et al 2007), there have been relatively few studies that have directly addressed the role of repeated psychostimulant exposure in altering impulsive choice behavior. Those that have (e.g., Richards et al 1999;Paine et al 2003;Roesch et al 2007;Simon et al 2007) suggest that chronic treatment with methamphetamine or cocaine increases impulsivity. However, a recent study by Winstanley et al (2007) showed that repeated cocaine treatment did not alter baseline levels of impulsive choice.…”

Section: Introductionmentioning

confidence: 99%

Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task

et al. 2008

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Rationale: Repeated amphetamine (AMPH) exposure is known to cause long-term changes in AMPH-induced locomotor behavior (i.e., sensitization) that are associated with similarly long-lasting changes in brain function. It is not clear, however, if such exposure produces long-lasting changes in a cognitive behavior that, in humans, is hypothesized to contribute to addiction. Objectives:To examine whether repeated AMPH exposure induces both locomotor sensitization and alters impulsive choice in a delay-discounting task.Methods: Adult, male Sprague-Dawley rats (n = 29) were pre-treated with 3.0 mg/kg AMPH or saline every other day for 20 days, and were then trained to lever press for small, immediately delivered food reinforcement or larger reinforcements delivered after delays. We subsequently assessed the effects of acute AMPH (0.1-2.0 mg/kg) on delay-discounting. Lastly, we tested for longlasting effects of pre-treatment by giving an AMPH challenge (3.0 mg/kg) one week after the final delay-discounting session.Results: Repeated AMPH produced sensitization to the drug's stereotypy-inducing effects, but did not alter acquisition or baseline behavior in the delay-discounting task. Following acute AMPH, impulsive choice and other measures of delay-discounting were altered, but to a similar extent in both saline-and AMPH-pretreated groups. The AMPH challenge, given ∼3 months after the last pretreatment injection, revealed sensitization was still evident. Conclusions:Our results suggest that one behavioral consequence of repeated AMPH exposure -sensitization -does not overlap with another potential outcome -increased impulsivity. Furthermore, the neuroadaptations known to be associated with sensitization may be somewhat distinct from those that lead to changes in impulsive choice.

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“…It has been suggested that a high level of impulsivity develops as a result of repeated exposure to abused drugs, and this in turn facilitates the development and/or maintenance of addiction (Jentsch and Taylor, 1999). Evidence supporting this hypothesis comes in part from studies using animal models, where repeated exposure to cocaine in rats leads to an increase in impulsive choice behavior relative to that observed in saline-treated controls (Paine et al, 2003;Roesch et al, 2007;Simon et al, 2007), and from clinical studies, where individuals who have been chronically exposed to cocaine show increases in impulsive choice relative to non-drug users or drug abstainers (for review, see Marsch, 2001 andReynolds, 2006). …”

Section: Introductionmentioning

confidence: 99%

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

Stanis

Burns

Sherrill

et al. 2008

Drug and Alcohol Dependence

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Heightened impulsivity and differential sensitivity to a drug's behavioral effects are traits that, individually, have been associated with chronic drug use and dependence. Here, we used an animal model to test whether individual differences in cocaine-induced activity are predictive of impulsive choice behavior. Adult, male Sprague-Dawley rats were given cocaine (10 mg/kg, i.p.) and classified into low or high cocaine responders (LCRs and HCRs, respectively) based on their locomotor response in an open-field arena. Rats were then trained in a delay-discounting task that offers a choice between immediately delivered, but smaller reinforcements, or larger reinforcements that are delivered after a delay. We also examined the effects of amphetamine (AMPH; 0.3-1.0 mg/kg) and the 5-HT 1A agonist 8-OH-DPAT (0.3-1.0 mg/kg) on delay discounting. Lastly, all rats were retested in the open-field to determine if phenotypes were stable. We observed baseline differences in choice behavior between the groups, with HCRs behaving more impulsively (i.e., choosing the small reinforcement) compared to LCRs. AMPH decreased choice of the large reinforcement in LCRs, but did not alter choice in HCRs. Impulsive choice was increased in both phenotypes following 8-OH-DPAT, with LCRs exhibiting changes across a wider range of delays. When cocaine-induced openfield behavior was retested, responses in LCRs were similar whereas HCRs showed evidence of tolerance. Our results suggest that differential sensitivity to cocaine-induced locomotion is predictive of impulsivity and the potential neurobiological differences in LCRs and HCRs may provide insight into mechanisms contributing to vulnerability for chronic drug use and/or dependence.

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Previous Cocaine Exposure Makes Rats Hypersensitive to Both Delay and Reward Magnitude

Cited by 109 publications

References 41 publications

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

Extended Access to Cocaine Self-Administration Produces Long-Lasting Prefrontal Cortex-Dependent Working Memory Impairments

Dissociation between long-lasting behavioral sensitization to amphetamine and impulsive choice in rats performing a delay-discounting task

Disparate cocaine-induced locomotion as a predictor of choice behavior in rats trained in a delay-discounting task

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