Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats

Bossert, Jennifer M.; Adhikary, Sweta; Laurent, Robyn St.; Marchant, Nathan J.; Wang, Hui Ling; Morales, Marisela; Shaham, Yavin

doi:10.1007/s00213-015-4060-5

Cited by 83 publications

(84 citation statements)

References 85 publications

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“…As noted above, vSUB inputs to AcbSh are important for context‐induced reinstatement. The vSUB neurons projecting to the AcbSh are recruited during context‐induced reinstatement of heroin seeking (Bossert et al ) and alcohol seeking (Marchant et al ). Pharmacological disconnection of the vSUB→AcbSh pathway prevents this reinstatement of heroin seeking (Bossert et al ) and chemogenetic disconnection of this pathway prevents this reinstatement after punishment‐imposed abstinence from alcohol seeking (Marchant et al ).…”

Section: Nucleus Accumbens Shellmentioning

confidence: 99%

“…The vSUB neurons projecting to the AcbSh are recruited during context‐induced reinstatement of heroin seeking (Bossert et al ) and alcohol seeking (Marchant et al ). Pharmacological disconnection of the vSUB→AcbSh pathway prevents this reinstatement of heroin seeking (Bossert et al ) and chemogenetic disconnection of this pathway prevents this reinstatement after punishment‐imposed abstinence from alcohol seeking (Marchant et al ). One attractive possibility is that glutamate derived from these vSUB inputs acts in combination with dopamine inputs from VTA to enable context‐induced reinstatement (Crombag et al ; Marchant et al ).…”

Section: Nucleus Accumbens Shellmentioning

confidence: 99%

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How contexts promote and prevent relapse to drug seeking

Khoo

Gibson

Prasad

et al. 2016

Genes Brain and Behavior

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The contexts where drugs are self-administered play an important role in regulating persistent drug taking and in relapse to such taking after periods of abstinence. Here, we review the behavioral and brain mechanisms enabling contexts to promote and prevent relapse to drug seeking. We review the key brain structures, their neuropharmacology and their connectivity. We discuss the similarities and differences between the mechanisms for context-induced reinstatement of drug seeking vs. other forms of relapse to drug seeking in animal models and we highlight the numerous deficits in our understanding. We emphasize that current understanding, although significant, defies explanations in terms of models at the level of brain structures and their connectivity. Rather, we show that there is significant functional compartmentalization and segregation within these structures during reinstatement and extinction of drug seeking that parallels their anatomical segregation into circuits and channels. A key challenge is to recognize this complexity, understand how these circuits and channels are organized, as well as understand how different modes of activity of ensembles of neurons within them promote abstinence or relapse to drug seeking.Keywords: Accumbens, addiction, amygdala, circuits, context-induced reinstatement, learning, orexin, prefrontal cortex, reinstatement, relapse, renewal Received 15 June 2016, revised 13 August 2016 and 30 August 2016, accepted for publication 31 August 2016Drug addiction remains a chronic condition imposing significant burdens on individuals, their families and communities. It is associated with increased rates of physical health problems including cardiovascular and liver disease; mental health problems including depression and anxiety; reduced levels of productivity, as well as higher utilization of health and social services (Lim et al. 2012;Nutt et al. 2010;Rehm et al. 2009). Considerable progress has been made in understanding the mechanisms of drug addiction including those contributing to the reinforcing effects of drugs of abuse and the escalation as well as loss of control over drug intake rendering it compulsive. A fundamental problem is relapse to drug taking after a period of abstinence. Rates of relapse are high and largely unchanged over a long period of time ( Basic work in neuroscience has provided significant information on the behavioral and brain mechanisms that initiate and sustain behavioral change. The relevance and importance of this work to the clinical problem of relapse is rightly judged on its clinical impact (Connor et al. 2016;Hall et al. 2014). There have been some successes, but much of this basic work is yet to achieve translational success (Heilig et al. 2016). There are many reasons for this but one theme that we explore here is that the mechanisms for behavioral change during extinction and reinstatement are significantly more nuanced than most current models of relapse to drug seeking allow. Here, we review current knowledge on how contexts promote and pr...

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Section: Nucleus Accumbens Shellmentioning

confidence: 99%

Section: Nucleus Accumbens Shellmentioning

confidence: 99%

How contexts promote and prevent relapse to drug seeking

Khoo

Gibson

Prasad

et al. 2016

Genes Brain and Behavior

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show abstract

“…Our previous research has focused on the neuropharmacology of context-induced heroin seeking (Bossert et al, 2007(Bossert et al, , 2009(Bossert et al, , 2011(Bossert et al, , 2012(Bossert et al, , 2016. However, in light of the current prescription opioid epidemic, we recently changed our focus to studying relapse to oxycodone, a prototypical prescription opioid drug that is widely used for pain management (Van Zee, 2009;Yaksh & Wallace, 2011).…”

Section: Introductionmentioning

confidence: 99%

Role of mu, but not delta or kappa, opioid receptors in context‐induced reinstatement of oxycodone seeking

Bossert

Hoots

Fredriksson

et al. 2018

Eur J of Neuroscience

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Relapse to non-medical use of prescription opioids often occurs after exposure to places previously associated with drug use. Here, we describe a rat model of context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction-induced abstinence. We also determined the role of mu, delta and kappa opioid receptors (MOR, DOR, KOR) in this reinstatement. We trained rats to self-administer oxycodone for 6 h/day in context A; lever pressing was paired with a discrete cue. Next, we extinguished the lever pressing in the presence of the discrete cue in context B and then tested the rats for reinstatement of oxycodone seeking in both contexts. We retrained rats to self-administer oxycodone in context A, re-extinguished their lever pressing in context B and retested them for reinstatement in both contexts. Prior to testing, we injected the rats with vehicle or antagonists of MOR (naltrexone; 0.5 or 1.0 mg/kg), DOR (naltrindole; 7.5 or 15 mg/kg) or KOR (LY2456302; 5 or 10 mg/kg). We also tested the effect of naltrexone, naltrindole and LY2456302 on oxycodone self-administration under fixed-ratio-1 (FR1) and progressive ratio (PR) reinforcement schedules. We observed context-induced reinstatement of oxycodone seeking after repeated cycles of drug self-administration and extinction. Naltrexone, but not naltrindole or LY2456302, injections decreased this reinstatement. Additionally, naltrexone increased oxycodone self-administration under the FR1 schedule and decreased oxycodone self-administration under the PR schedule; naltrindole and LY2456302 were ineffective. Results demonstrate a critical role of MOR, but not DOR or KOR, in context-induced reinstatement of oxycodone seeking and oxycodone self-administration.

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“…vSUB inputs to AcbSh are important for context‐induced reinstatement. vSUB neurons projecting to the AcbSh express the c‐Fos protein during context‐induced reinstatement of heroin (Bossert et al ., ) and alcohol seeking (Marchant et al ., ). Pharmacological disconnection of vSUB → AcbSh pathway prevents context‐induced reinstatement of heroin seeking (Bossert et al ., ) and chemogenetic disconnection of this pathway prevents this reinstatement after punishment‐imposed abstinence from alcohol seeking (Marchant et al ., ).…”

Section: Linking Dual Roles In Extinction and Reinstatement To Nucleumentioning

confidence: 99%

“…vSUB inputs to AcbSh are important for context-induced reinstatement. vSUB neurons projecting to the AcbSh express the c-Fos protein during context-induced reinstatement of heroin (Bossert et al, 2016) and alcohol seeking . Pharmacological disconnection of vSUB ?…”

Section: Linking Dual Roles In Extinction and Reinstatement To Nucleumentioning

confidence: 99%

The nucleus accumbens shell in reinstatement and extinction of drug seeking

Gibson

Millan

McNally

2018

Eur J of Neuroscience

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The contexts where drugs are self-administered have important control over relapse and extinction of drug-seeking behavior. The nucleus accumbens shell (AcbSh) is essential to this contextual control over drug-seeking behavior. It has been consistently implicated in both the expression of context-induced reinstatement and the expression of extinction, across a variety of drug classes and other rewards. Here, we review the evidence linking AcbSh to the extinction and reinstatement of drug seeking. We consider whether this dual role can be linked to known heterogeneities in AcbSh cell types, their major afferents, and their major efferents. We show that although these heterogeneities are each important and can determine extinction vs. reinstatement, they do not seem adequate to explain the body of findings from the behavioral literature. Rather, we suggest that this functional specialization of AcbSh may be more profitably viewed in terms of the segregation and compartmentalization of AcbSh channels.

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Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats

Cited by 83 publications

References 85 publications

How contexts promote and prevent relapse to drug seeking

How contexts promote and prevent relapse to drug seeking

Role of mu, but not delta or kappa, opioid receptors in context‐induced reinstatement of oxycodone seeking

The nucleus accumbens shell in reinstatement and extinction of drug seeking

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