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

Gobin, Christina; Shallcross, John; Schwendt, Marek

doi:10.1016/j.nlm.2019.03.007

Cited by 19 publications

(22 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These effects of MTEP were acute and did not persist past the drug treatment period (denoted here as washout). We recently found that the same regimen of cocaine selfadministration used in the present study produced deficits in working memory performance that persisted over weeks of drug-free abstinence (Gobin et al 2019). As all rats used in the current study had a cocaine history, their working memory ability was likely already impaired prior to MTEP administration, indicating that treatment with this class of drugs may produce further cognitive impairment in recovering addicts.…”

Section: Discussionsupporting

confidence: 51%

“…And further, in these tasks facilitatory effects of CDPPB typically applied to new learning. In contrast, we have shown that chronic cocaine produces sustained, but relatively mild cognitive impairment in rats (Gobin and Schwendt 2017;Gobin et al 2019) and this study). Also in this study, CDPPB was evaluated on rats who had an extensive history of DMS training.…”

Section: Discussioncontrasting

confidence: 50%

“…Furthermore, the efficacy of these modulators in enhancing mGlu5 activity depends on the concentration of endogenous/orthostatic agonist (extracellular glutamate) and on mGlu5 agonist-modulator cooperativity factor (Stansley and Conn 2019). As such, region-specific dysregulation of mGlu5 signaling (Gobin et al 2019), mGlu5 function (Ben-Shahar et al 2013) and glutamate homeostasis (Knackstedt & Kalivas, 2009) after chronic cocaine may further determine circuit-specific effects of systemic MTEP and CDPPB administration.…”

Section: Discussionmentioning

confidence: 99%

“…All rats were implanted with jugular catheters and submitted to cocaine self-administration (SA) as previously described (Gobin and Schwendt 2017;Gobin et al 2019). Rats were anesthetized with ketamine (87.5 mg/kg, i.p.)…”

Section: Surgery and Cocaine Self-administrationmentioning

confidence: 99%

“…During this period, the effects of repeated treatment with mGlu5 allosteric modulators on working memory performance and cocaine-seeking were evaluated in the delayed-match-to-sample (DMS) task and upon re-exposure to cocaine paired context and cues (relapse test). Using this experimental design, we have recently reported that extended-access cocaine self-administration produces not only robust cocaine-seeking, but also persistent working memory deficits that are related to long-term changes in metabolic activity and mGlu5 expression within the prefrontal cortex (Gobin et al 2019). Here, we tested the following hypotheses: (1) chronic systemic administration of an mGlu5 NAM will impair working memory (2) chronic systemic treatment with an mGlu5 PAM, will improve working memory and (3) acute administration of the mGlu5 NAM, but not PAM will attenuate cocaineseeking.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Gobin

Schwendt

2019

Preprint

Self Cite

View full text Add to dashboard Cite

Rationale: Cocaine 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. Objectives: Here 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. Methods: Adult 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. Results: MTEP 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. Conclusions: These 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.

show abstract

Section: Discussionsupporting

confidence: 51%

Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 99%

Section: Surgery and Cocaine Self-administrationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

Gobin

Schwendt

2019

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Working and Reference Memory Impairments Induced by Passive Chronic Cocaine Administration in Mice

Mañas‐Padilla

Ávila‐Gámiz

Gil-Rodríguez

et al. 2021

Methods for Preclinical Research in Addiction

View full text Add to dashboard Cite

Molecular and circuit mechanisms regulating cocaine memory

Bender

Torregrossa

2020

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

Risk of relapse is a major challenge in the treatment of substance use disorders. Several types of learning and memory mechanisms are involved in substance use and have implications for relapse. Associative memories form between the effects of drugs and the surrounding environmental stimuli, and exposure to these stimuli during abstinence causes stress and triggers drug craving, which can lead to relapse. Understanding the neural underpinnings of how these associations are formed and maintained will inform future advances in treatment practices. A large body of research has expanded our knowledge of how associative memories are acquired and consolidated, how they are updated through reactivation and reconsolidation, and how competing extinction memories are formed. This review will focus on the vast literature examining the mechanisms of cocaine Pavlovian associative memories with an emphasis on the molecular memory mechanisms and circuits involved in the consolidation, reconsolidation, and extinction of these memories. Additional research elucidating the specific signaling pathways, mechanisms of synaptic plasticity, and epigenetic regulation of gene expression in the circuits involved in associative learning will reveal more distinctions between consolidation, reconsolidation, and extinction learning that can be applied to the treatment of substance use disorders.

show abstract

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

Cited by 19 publications

References 106 publications

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

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

Working and Reference Memory Impairments Induced by Passive Chronic Cocaine Administration in Mice

Molecular and circuit mechanisms regulating cocaine memory

Contact Info

Product

Resources

About