Steady-state methadone blocks cocaine seeking and cocaine-induced gene expression alterations in the rat brain

Leri, Francesco; Zhou, Yan; Goddard, Benjamin; Levy, AnneMarie; Jacklin, Derek L.; Kreek, Mary Jeanne

doi:10.1016/j.euroneuro.2008.09.004

Cited by 34 publications

(33 citation statements)

References 86 publications

(101 reference statements)

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“…Both reduced availability of D2 receptor binding and decreased D2 gene expression in the striatum have been consistently associated with heroin cravings in humans [e.g., 38, 39] and cocaine seeking in animals [e.g., 25, 26]. In the present study, we observed a down-regulation of CPu D2 mRNA levels in the H-RI rats.…”

Section: Discussionsupporting

confidence: 66%

“…Nine days after heroin self-administration, specific brain regions were collected to quantify AVP, POMC and orexin gene expressions, and the alterations were analyzed in the H-RI and L-RI groups. Because availability of dopamine D2 receptor (D2) binding and D2 gene expression in the striatum have been associated with cocaine seeking [25, 26], we also determined if the changes in striatal D2 expression, as well as in the stress hormones (ACTH, corticosterone and prolactin), were correlated with vulnerability to stress-induced heroin-seeking.…”

Section: Introductionmentioning

confidence: 99%

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Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: Vulnerability to relapse to heroin-seeking in rats

Zhou

Leri

Cummins

et al. 2015

Physiology & Behavior

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Individual vulnerability to stress-induced relapse during abstinence from chronic heroin exposure is a key feature of opiate addiction, with limited studies on this topic. Arginine vasopressin (AVP) and its V1b receptor, components of the brain stress responsive systems, play a role in heroin-seeking behavior triggered by foot shock (FS) stress in rats. In this study, we tested whether individual differences in the FS-induced heroin-seeking were associated with alterations of AVP and V1b, as well as other stress responsive systems, including pro-opiomelanocortin (POMC), orexin, plasma ACTH and corticosterone, as well as dopamine D2 receptor (D2) and plasma prolactin. Sprague-Dawley rats were subjected to 3-hour intravenous heroin self-administration (SA) and then tested in extinction, FS-induced and heroin priming-induced reinstatements. The rats that self-administered heroin were divided to high and low reinstatement responders induced by FS (H-RI; L-RI). Over SA sessions, both the H-RI and L-RI displayed similar active lever responding, heroin infusion and total heroin intake. Compared to the L-RI, however, the H-RI showed greater active lever responses during stress-induced reinstatement, with higher AVP mRNA levels in medial/basolateral amygdala and lower D2 mRNA levels in caudate putamen. However, heroin priming resulted in similar reinstatement in both groups and produced similarly low POMC and high orexin mRNA levels in hypothalamus. Our results indicate that: 1) enhanced amygdalar AVP and reduced striatal D2 expression may be related to individual vulnerability to stress-induced reinstatement of heroin- seeking; and 2) heroin abstinence-associated alterations of hypothalamic orexin and POMC expression may be involved in drug priming-induced heroin-seeking.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: Vulnerability to relapse to heroin-seeking in rats

Zhou

Leri

Cummins

et al. 2015

Physiology & Behavior

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“…For instance, Davis & Smith (1976) paired a stimulus with drug delivery and showed that making stimulus-presentation response-contingent maintained responding (see also Leri et al 2009). Thus, drug-paired stimuli can at least temporarily maintain behavior as a result of Pavlovian learning.…”

Section: Introductionmentioning

confidence: 99%

Conditioned stimuli’s role in relapse: preclinical research on Pavlovian-Instrumental-Transfer

2016

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Rationale and Objective Pavlovian learning is central to many theories of addiction. In these theories, stimuli paired with drug ingestion become Conditioned Stimuli (CS) and subsequently elicit drug-seeking and -taking. However in most relevant studies, Pavlovian and instrumental learning are confounded. This confound may be avoided in Pavlovian-Instrumental-Transfer (PIT) procedures. In PIT, Pavlovian and instrumental learning are established separately, and then combined. In order to better understand the role of CSs in addiction, we review the relevant studies using PIT. Findings We identified seven articles examining PIT effects of ethanol- or cocaine-paired CSs. Under at least one condition six of these articles reported CS-elicited increases in responding previously maintained by drug. However, the only study using the optimal control condition failed to find a CS-elicited increase. Two studies examining CS specificity found the CS also increased responding maintained by a different reinforcer. Two studies examined if CSs elicit increases in actual drug-taking. Both failed to find CS-elicited increases, i.e., no study shows CS-elicited increases in actual drug-taking. Further, CS-elicited increases in extinguished responding are short-lived. Conclusions These findings are not entirely consistent with Pavlovian learning playing a central role in addiction. However, design issues can explain most of these inconsistencies. Studies without these design issues are needed. Additionally, existing theories hypothesize drug-paired CSs increase drug-taking by increasing motivation, by eliciting conditioned responses that make drug-seeking more probable, or by a combination of these. Work distinguishing between these mechanisms would also be useful.

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“…In addition, the EOS has been implicated in drug-seeking behavior (Leri, Zhou, Goddard, Cummins, & Kreek, 2006;Leri et al, 2009), craving, and relapse (Ghitza et al, 2010;Gorelick et al, 2005) in cocaine addiction. Thus, alterations in the EOS, especially the expression of the KOR and MOR, can potentially exacerbate the risk of cocaine addiction.…”

Section: Cocaine and Hiv-1mentioning

confidence: 99%

NeuroHIV and Use of Addictive Substances

Chang

Connaghan

Wei

et al. 2014

International Review of Neurobiology

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Steady-state methadone blocks cocaine seeking and cocaine-induced gene expression alterations in the rat brain

Cited by 34 publications

References 86 publications

Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: Vulnerability to relapse to heroin-seeking in rats

Individual differences in gene expression of vasopressin, D2 receptor, POMC and orexin: Vulnerability to relapse to heroin-seeking in rats

Conditioned stimuli’s role in relapse: preclinical research on Pavlovian-Instrumental-Transfer

NeuroHIV and Use of Addictive Substances

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