Escalation of Cocaine Intake and Incubation of Cocaine Seeking Are Correlated with Dissociable Neuronal Processes in Different Accumbens Subregions

Guillem, Karine; Ahmed, Serge H.; Peoples, Laura L.

doi:10.1016/j.biopsych.2013.08.032

Cited by 60 publications

(69 citation statements)

References 49 publications

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“…Individuals with the most attenuated amphetamine-induced DA were more likely to choose cocaine over alternative monetary rewards (Martinez et al, 2007), which is strikingly consistent with the neurochemistry and choice behavior of CP rats. While others have reported reduced DA responses following cocaine self-administration (Ferris et al, 2011;Gerrits et al, 2002), the longitudinal nature of our experiment revealed that the attenuation occurred after cocaine preferences developed, which may contribute to the increased cocaine intake of CP rats (Guillem et al, 2013;Lau and Sun, 2002;Wise et al, 1995). Our data from PP rats suggest that cocaine exposure itself does not attenuate cocaine-induced DA in the NAc, which is consistent with other studies linking escalation (but not intake) to changes in DA neurotransmission (Willuhn et al, 2014).…”

Section: Discussionsupporting

confidence: 88%

The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats

Perry

Westenbroek

Jagannathan

et al. 2015

Neuropsychopharmacol

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Cocaine dependence is characterized by compulsive drug taking and reduced involvement in social, occupational, or recreational activities. Unraveling the diverse mechanisms contributing to the loss-of-interest in these 'non-drug' pursuits is essential for understanding the neurobiology of addiction and could provide additional targets for treating addiction. The study objectives were to examine changes in cocaine-induced dopamine (DA) overflow in the nucleus accumbens (NAc) over the course of self-administration and determine the roles of α1-and β-adrenergic receptors (AR) in the loss-of-interest in food rewards following the development of an addicted phenotype in male and female rats. Subjects were given access to cocaine and palatable food pellets in a choice self-administration paradigm to identify 'addicted' cocaine-preferring (CP) individuals and resistant pellet-preferring (PP) individuals based on their patterns of self-administration over 7 weeks. Cocaine-induced DA overflow in the NAc was examined with microdialysis early and late during self-administration (weeks 2 and 7). Subjects were treated in counter-balanced order with propranolol (β-AR antagonist), terazosin (α1-AR antagonist), or vehicle for an additional 3 weeks of self-administration. CP rats displayed increased motivation for cocaine and attenuated motivation for pellets following the development of cocaine preferences. In females, the estrous cycle affected pellet, but not cocaine, self-administration. CP rats displayed attenuated cocaine-induced DA overflow in the NAc. Propranolol enhanced cocaine reinforcement and reduced pellet intake, whereas terazosin enhanced motivation for pellets and reversed preferences in a subset of CP rats. The implications of these results for the treatment of addiction are discussed.

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Section: Discussionsupporting

confidence: 88%

The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats

Perry

Westenbroek

Jagannathan

et al. 2015

Neuropsychopharmacol

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“…However, after ~1 month of withdrawal from extended-access cocaine self-administration, high conductance Ca 2+ -permeable AMPARs (CP-AMPARs) accumulate in NAc core synapses (18–23) and thereafter their activation is required for the expression of incubated cocaine craving (18,23). This is consistent with other evidence that enhanced activation of NAc core MSN is critical for incubation (24–26), as well as cocaine seeking in other models (e.g., 27,28). CP-AMPAR plasticity occurs in concert with plasticity of group I mGlu-mediated synaptic depression in the NAc core.…”

Section: Introductionsupporting

confidence: 92%

AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving

Scheyer¹,

Loweth²,

Christian³

et al. 2016

Biological Psychiatry

108

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BACKGROUND The incubation of cue-induced drug craving in rodents provides a model of persistent vulnerability to craving and relapse in human addicts. After prolonged withdrawal, incubated cocaine craving depends on strengthening of nucleus accumbens (NAc) core synapses through incorporation of Ca2+-permeable AMPA receptors (CP-AMPARs). Through mGlu1-mediated synaptic depression, mGlu1 positive allosteric modulators (PAMs) remove CP-AMPARs from these synapses and thereby reduce cocaine craving. This study aimed to determine if similar plasticity accompanies incubation of methamphetamine craving. METHODS Rats self-administered saline or methamphetamine under extended-access conditions. Cue-induced seeking tests demonstrated incubation of methamphetamine craving. After withdrawal periods ranging from 1 to >40 days, rats underwent one of the following procedures: 1) whole-cell patch clamp recordings to characterize AMPAR transmission, 2) intra-NAc core injection of the CP-AMPAR antagonist 1-napthyl acetyl spermine (naspm) prior to a seeking test, or 3) systemic administration of an mGlu1 PAM prior to a seeking test. RESULTS Incubation of methamphetamine craving was associated with CP-AMPAR accumulation in NAc core, and both effects were maximal after ~1 week of withdrawal. Expression of incubated craving was decreased by intra-NAc naspm injection or systemic mGlu1 PAM administration. CONCLUSIONS These results are the first to demonstrate a role for the NAc in the incubation of methamphetamine craving and describe adaptations in synaptic transmission associated with this model. They establish that incubation of craving and associated CP-AMPAR plasticity occur much more rapidly during withdrawal from methamphetamine than cocaine. However, a common mGlu1-based therapeutic strategy may be helpful for recovering cocaine and methamphetamine addicts.

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“…The relative enlargement of neuronal coding for the cocaine cue is consistent with the incubation of drug craving seen after cocaine withdrawal (Grimm et al, 2001). Another study used prolonged access to cocaine self-administration, and in vivo electrophysiological recordings in the NAc were performed during escalation of cocaine intake, after 30 days of forced abstinence, and during cocaine re-exposure (Guillem et al, 2014). The authors concluded that the incubation of cocaine seeking observed after the abstinence phase was significantly and selectively correlated to an increase in the proportion of neurons that fired phasically during cocaine seeking.…”

Section: Could the T-sp Be Embedded In A Neuronal Network Specificmentioning

confidence: 99%

Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior

Bobadilla

Heinsbroek

Gipson

et al. 2017

Progress in Brain Research

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The idea that interconnected neuronal ensembles code for specific behaviors has been around for decades; however, recent technical improvements allow studying these networks and their causal role in initiating and maintaining behavior. In particular, the role of ensembles in drug-seeking behaviors in the context of addiction is being actively investigated. Concurrent with breakthroughs in quantifying ensembles, research has identified a role for synaptic glutamate spillover during relapse. In particular, the transient relapse-associated changes in glutamatergic synapses on accumbens neurons, as well as in adjacent astroglia and extracellular matrix, are key elements of the synaptic plasticity encoded by drug use and the metaplasticity induced by drug-associated cues that precipitate drug seeking behaviors. Here, we briefly review the recent discoveries related to ensembles in the addiction field, and then endeavor to link these discoveries with drug-induced striatal plasticity and cue-induced metaplasticity towards deeper neurobiological understandings of drug-seeking.

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Escalation of Cocaine Intake and Incubation of Cocaine Seeking Are Correlated with Dissociable Neuronal Processes in Different Accumbens Subregions

Cited by 60 publications

References 49 publications

The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats

The Roles of Dopamine and α1-Adrenergic Receptors in Cocaine Preferences in Female and Male Rats

AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving

Corticostriatal plasticity, neuronal ensembles, and regulation of drug-seeking behavior

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