Effects of persistent cocaine self-administration on amygdala-dependent and dorsal striatum-dependent learning in rats

Udo, Tomoko; Ugalde, Francisco; DiPietro, Nina; Eichenbaum, Howard; Kantak, Kathleen M.

doi:10.1007/s00213-003-1734-1

Cited by 23 publications

(30 citation statements)

References 63 publications

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“…It is possible, though, that this enhanced LTP could account for the better performance during testing of the subjects which had received 0.1 mg/kg cocaine before training. Other studies on both acute and frequent cocaine intake have revealed the disruption of amygdala-dependent learning, as well [29,48]. The present effects on both context and tone conditioning suggest that both hippocampus and amygdala-dependent learning can be disrupted even by acute, moderate cocaine administration, while a very low dose can enhance this learning.…”

Section: Discussionsupporting

confidence: 55%

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Wood

Fay

Sage

et al. 2007

Behavioural Brain Research

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Emerging evidence suggests that cocaine and other drugs of abuse can interfere with many aspects of cognitive functioning. The authors examined the effects of 0.1 -15 mg/kg of cocaine on Pavlovian contextual and cued fear conditioning in mice. As expected, pre-training cocaine dose-dependently produced hyperactivity and disrupted freezing. Surprisingly, when the mice were tested off-drug later, the group pre-treated with a moderate dose of cocaine (15 mg/kg) displayed significantly less contextual and cued memory, compared to saline control animals. Conversely, mice pre-treated with a very low dose of cocaine (0.1 mg/kg) showed significantly enhanced fear memory for both context and tone, compared to controls. These results were not due to cocaine's anesthetic effects, as shock reactivity was unaffected by cocaine. The data suggest that despite cocaine's reputation as a performance-enhancing and anxiogenic drug, this effect is seen only at very low doses, whereas a moderate dose disrupts hippocampus and amygdala-dependent fear conditioning. KeywordsHippocampus; Amygdala; Freezing; Memory A growing body of evidence supports the view that drugs of abuse interfere with many aspects of cognitive functioning. For example, cocaine use has been linked to deficits in such cognitive areas as attention, cognitive flexibility, and short-term and working memory [34,43]. However, these findings in humans are controversial as cocaine use is naturally confounded with many other variables [e.g. 23, 27, 31]. Some studies, in fact, provide evidence for enhancement of certain cognitive abilities in cocaine users [e.g. 27, 50]. Relatively few studies in animals have examined the effects of cocaine on learning outside of the realm of addiction (e.g. selfadministration, place preference, sensitization). Indeed, several studies have focused on the mechanisms underlying addiction, including structural plasticity [see 41 for review], but few have examined the acute, behavioral effects of cocaine in rodents on simple learning and memory paradigms. We believe that most researchers implicitly assume, as we once did, that cocaine, as a psychostimulant, would naturally enhance learning and memory. However, evidence now exists linking cocaine use with specific cognitive deficits [5,25,34,43] as well as with general problems such as unemployment [35]. Moreover, a view has emerged that addictive drugs such as cocaine may work by taking control of critical reinforcement-related learning and memory circuits in the brain [28]. If cocaine modulates such circuits, then it may 1 Address correspondence and reprint requests to: Suzanne C. Wood,

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Section: Discussionsupporting

confidence: 55%

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Wood

Fay

Sage

et al. 2007

Behavioural Brain Research

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“…Some insight into the time course of the effects of contingent and passive cocaine administration on stimulusreward learning in adult rats stems from consideration of an earlier investigation (Udo et al 2004). In that study, contingent and passive administration of cocaine produced deficits in conditioned cue preference, whether rats were under the influence of cocaine at the time of testing or after a 1-day drug-free period.…”

Section: Discussionmentioning

confidence: 98%

“…This task requires the intact functioning of the amygdala memory system for acquisition and expression of stimulus-reward learning (McDonald and White 1993;Kantak et al 2001). As clinical studies typically assess neurocognitive functioning of adult cocaine addicts during a forced or self-imposed abstinence period (Bolla et al 1999(Bolla et al , 2003Grant et al 2000;Di Sclafani et al 2002;Simon et al 2002;Pace-Schott et al 2005), using an experimental design that incorporates a drug-free period is relevant from a translational perspective and extends our earlier work in adult rats tested under the influence of cocaine (Udo et al 2004;Kantak et al 2005).…”

mentioning

confidence: 96%

“…In adult male rats self-administering cocaine, previous research using a yoked-triad design demonstrated deficits in tasks requiring the intact functioning of the amygdala, orbital prefrontal cortex, and medial prefrontal cortex memory systems but no deficits in tasks requiring the intact functioning of the dorsal striatum or hippocampus memory systems (Udo et al 2004;Kantak et al 2005). Using a fivechoice serial reaction time task (5-CSRTT), which measures attention that requires the intact functioning of the medial prefrontal cortex, it was revealed that rats with cocaine selfadministration experience had selective impairments in attention when tested after a 1-day drug-free period compared to yoked-saline controls (Dalley et al 2005).…”

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confidence: 97%

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Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Kerstetter

Kantak

2007

Psychopharmacology

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“…In a recent investigation, Udo et al (2004) established that certain forms of learning are susceptible to disruption by prior intravenous (i.v.) cocaine self-administration, namely the acquisition of a conditioned cue preference task.…”

Section: Introductionmentioning

confidence: 99%

Cognitive Sequelae of Intravenous Amphetamine Self-Administration in Rats: Evidence for Selective Effects on Attentional Performance

Dalley

Theobald

Berry

et al. 2004

Neuropsychopharmacol

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Characterizing the nature and severity of cognitive deficits associated with chronic stimulant abuse may provide new insights into the neural substrates of drug addiction because such deficits may contribute to the chronic relapsing nature of compulsive drug use. This investigation examines in rats the long-term cognitive consequences of intravenously self-administered amphetamine, specifically on performance of a 5-choice serial reaction time task (5-CSRTT), which assesses visuo-spatial attention and impulsivity. Rats experienced 5 days of intravenous (i.v.) amphetamine self-administration and were then withdrawn for a period of 9 days, during which time testing on the 5-CSRTT took place. This was repeated on five consecutive occasions for a period of 10 weeks. Controls experienced identical training on the 5-CSRTT but during the self-administration sessions received yoked i.v. infusions of normal saline. The results reveal a selective and reproducible pattern of deficits on the 5-CSRTT following repeated withdrawal from amphetamine self-administration, with deleterious effects on the speed and accuracy of responding as well as increased omission errors. Premature (impulsive) responding, perseveration, and food consumption latencies were not significantly affected. Deficits in attentional performance fully recovered 4-5 days after amphetamine cessation and there was no evidence of any long-term disturbances, even when the attentional load was increased. However, following a 2-month abstinence period, abnormalities in the subsequent effects of acute noncontingent amphetamine were found, with increased omissions, slower response times, and reduced impulsivity. Thus, contingent i.v. amphetamine administration has both short-and long-term consequences, which may be relevant to the complex disturbances that accompany drug addiction.

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Effects of persistent cocaine self-administration on amygdala-dependent and dorsal striatum-dependent learning in rats

Cited by 23 publications

References 63 publications

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Cocaine and Pavlovian fear conditioning: Dose–effect analysis

Differential effects of self-administered cocaine in adolescent and adult rats on stimulus–reward learning

Cognitive Sequelae of Intravenous Amphetamine Self-Administration in Rats: Evidence for Selective Effects on Attentional Performance

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