Neurobiological substrates of persistent working memory deficits and cocaine-seeking in the prelimbic cortex of rats with a history of extended access to cocaine self-administration

AbstractThe anterior insular cortex (AIC) has been implicated in addictive behaviour, including the loss of control over drug intake, craving and the propensity to relapse. Evidence suggests that the influence of the AIC on drug-related behaviours is complex since in rats exposed to extended access to cocaine self-administration, the AIC was shown to exert a state-dependent, bidirectional influence on the development and expression of loss of control over drug intake, facilitating the latter but impairing the former. However, it is unclear whether this influence of the AIC is confined to stimulant drugs that have marked peripheral sympathomimetic and anxiogenic effects or whether it extends to other addictive drugs, such as opiates, that lack overt acute aversive peripheral effects. Thus, we investigated in outbred rats the effects of bilateral excitotoxic lesions of AIC, induced both prior to or after long-term exposure to extended access heroin self-administration, on the development and maintenance of escalated heroin intake and the subsequent vulnerability to relapse following abstinence. Compared to sham-surgeries, pre-exposure AIC lesions had no effect on the development of loss of control over heroin intake, but lesions made after a history of escalated heroin intake potentiated escalation and also enhanced responding at relapse. These data show that the AIC inhibits or limits the loss of control over heroin intake and propensity to relapse, in marked contrast to its influence on the loss of control over cocaine intake.

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Activation of TAAR1 attenuates extended access of cocaine self‐administration and stress‐induced reinstatement of cocaine‐seeking

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.664.10 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Jian‐Feng Liu ◽

Bernard Johnson ◽

Robert Seaman ◽

Ruyan Wu ◽

Yanan Zhang ◽

...

Keyword(s):

Self Administration ◽

Cocaine Seeking ◽

Extended Access

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Persistent palatable food preference in rats with a history of limited and extended access to methamphetamine self-administration

Addiction Biology ◽

10.1111/adb.12220 ◽

2015 ◽

Vol 20 (5) ◽

pp. 913-926 ◽

Cited By ~ 39

Author(s):

Daniele Caprioli ◽

Tamara Zeric ◽

Eric B. Thorndike ◽

Marco Venniro

Keyword(s):

Food Preference ◽

Palatable Food ◽

Self Administration ◽

Extended Access ◽

History Of

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Visual working memory deficits in undergraduates with a history of mild traumatic brain injury

Attention Perception & Psychophysics ◽

10.3758/s13414-019-01774-9 ◽

2019 ◽

Vol 81 (8) ◽

pp. 2597-2603 ◽

Cited By ~ 1

Author(s):

Hector Arciniega ◽

Alexandrea Kilgore-Gomez ◽

Alison Harris ◽

Dwight J. Peterson ◽

Jaclyn McBride ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Working Memory ◽

Brain Injury ◽

Visual Working Memory ◽

Mild Traumatic Brain Injury ◽

Memory Deficits ◽

History Of

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TA 1 agonists attenuate extended‐access cocaine self‐administration and yohimbine‐induced reinstatement of cocaine‐seeking

British Journal of Pharmacology ◽

10.1111/bph.15061 ◽

2020 ◽

Vol 177 (15) ◽

pp. 3403-3414 ◽

Cited By ~ 1

Author(s):

Jianfeng Liu ◽

Bernard Johnson ◽

Ruyan Wu ◽

Robert Seaman ◽

Jimmy Vu ◽

...

Keyword(s):

Self Administration ◽

Cocaine Seeking ◽

Extended Access

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Working memory deficits and alterations of ERK and CREB phosphorylation following withdrawal from cocaine self-administration

Pharmacological Reports ◽

10.1016/j.pharep.2015.01.013 ◽

2015 ◽

Vol 67 (5) ◽

pp. 881-889 ◽

Cited By ~ 8

Author(s):

Katarzyna Fijał ◽

Ewa Nowak ◽

Monika Leśkiewicz ◽

Bogusława Budziszewska ◽

Małgorzata Filip

Keyword(s):

Working Memory ◽

Memory Deficits ◽

Self Administration ◽

Creb Phosphorylation

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The cognitive cost of reducing relapse to cocaine-seeking with mGlu5 allosteric modulators

10.1101/628388 ◽

2019 ◽

Author(s):

Christina Gobin ◽

Marek Schwendt

Keyword(s):

Working Memory ◽

Cognitive Function ◽

Metabotropic Glutamate Receptor ◽

Memory Performance ◽

Repeated Treatment ◽

Allosteric Modulators ◽

Sprague Dawley ◽

Self Administration ◽

Cocaine Seeking ◽

Prolonged Abstinence

AbstractRationaleCocaine use disorder (CUD) remains difficult to treat with no FDA-approved medications to reduce relapse. Antagonism of metabotropic glutamate receptor 5 (mGlu5) has been demonstrated to decrease cocaine seeking but may also further compromise cognitive function in long-term cocaine users.ObjectivesHere we assessed the effect of repeated administration of negative or positive allosteric modulators (NAM or PAM) of mGlu5 on both cognitive performance and (context+cue)-primed cocaine seeking after prolonged abstinence.MethodsAdult male Sprague-Dawley rats underwent 6 days of short-access (1 h/day) and 12 days of long-access (6 h/day) cocaine self-administration. Rats were then trained and tested in a delayed-match-to-sample (DMS) task to establish baseline working memory performance over a five-day block of testing. Next, rats received daily systemic administration of the mGlu5 NAM MTEP (3 mg/kg), mGlu5 PAM CDPPB (30 mg/kg) or vehicle prior to DMS testing during a block of five days, followed by a 5-day washout DMS testing block.ResultsMTEP and CDPPB decreased drug seeking in response to cocaine-associated cues after prolonged abstinence. However, repeated treatment with MTEP impaired working memory, while CDPPB had no effects on performance.ConclusionsThese results emphasize the relevance of evaluating cognitive function within the context of investigating pharmacotherapies to treat CUD. Further research is needed to determine how two mechanistically different pharmacological compounds can exert the same behavioral effects to reduce cocaine seeking.

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