A critical role of nucleus accumbens dopamine D1-family receptors in renewal of alcohol seeking after punishment-imposed abstinence.

Marchant, Nathan J.; Kaganovsky, Konstantin

doi:10.1037/bne0000050

Cited by 33 publications

(20 citation statements)

References 55 publications

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“…Finally, NAc dopamine is known to play a role in food reward (Wise, 2004), and from this perspective the observation that hM4Di inhibition of local Drd1-or Drd2-expressing neurons has no effect on food self-administration and seeking is unexpected. However, in our study we trained our mice under low effort (FR1) reinforcement schedule and under these training conditions, we and others found that NAc injections of SCH23390 have no effect on food selfadministration in rats (Bossert et al, 2007;Marchant and Kaganovsky, 2015). Our negative food data using a chemogenetic approach in mice and the previous negative data mentioned above using intracranial drug injections agree with Salamone's (2016) notion of the selective role of NAc dopamine in controlling high-effort but not low-effort food-reinforced responding.…”

Section: Methodological and Experimental Considerationssupporting

confidence: 83%

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

et al. 2019

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We recently developed a mouse model of appetitive operant aggression and reported that adult male outbred CD-1 mice lever-press for the opportunity to attack subordinate male mice and relapse to aggression seeking during abstinence. Here we studied the role of nucleus accumbens (NAc) dopamine receptor (Drd)1-and Drd2-expressing neurons in aggression self-administration and aggression seeking. We trained CD-1 mice to self-administer intruders (9 d, 12 trials/d) and tested them for aggression self-administration and aggression seeking on abstinence Day 1. We used immunohistochemistry and in situ hybridization to measure the neuronal activity marker Fos in the NAc, and cell-type-specific colocalization of Fos with Drd1-and Drd2-expressing neurons. To test the causal role of Drd1-and Drd2-expressing neurons, we validated a transgenic hybrid breeding strategy crossing inbred Drd1-Cre and Drd2-Cre transgenic mice with outbred CD-1 mice and used cell-type-specific Cre-DREADD (hM4Di) to inhibit NAc Drd1-and Drd2-expressing neuron activity. We found that aggression self-administration and aggression seeking induced higher Fos expression in NAc shell than in core, that Fos colocalized with Drd1 and Drd2 in both subregions, and that chemogenetic inhibition of Drd1-, but not Drd2-, expressing neurons decreased aggression self-administration and aggression seeking. Results indicate a cell-type-specific role of Drd1-expressing neurons that is critical for both aggression self-administration and aggression seeking. Our study also validates a simple breeding strategy between outbred CD-1 mice and inbred C57-based Cre lines that can be used to study cell-type and circuit mechanisms of aggression reward and relapse.Aggression is often comorbid with neuropsychiatric diseases, including drug addiction. One form, appetitive aggression, exhibits symptomatology that mimics that of drug addiction and is hypothesized to be due to dysregulation of addiction-related reward circuits. However, our mechanistic understanding of the circuitry modulating appetitive operant aggression is limited. Here we used a novel mouse model of aggression self-administration and relapse, in combination with immunohistochemistry, in situ hybridization, and chemogenetic manipulations to examine how cell types in the nucleus accumbens are recruited for, and control, operant aggression self-administration and aggression seeking on abstinence Day 1. We found that one population, dopamine receptor 1-expressing neurons, act as a critical modulator of operant aggression reward and aggression seeking.

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Section: Methodological and Experimental Considerationssupporting

confidence: 83%

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

et al. 2019

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“…It is also unlikely that motor deficits or other non-specific behavioral effects of the drugs decreased context-induced reinstatement, because we previously found that bilateral injections of M+B into vSub or SCH 23390 into NAc shell have no effect on high rate food-reinforced responding (Bossert et al 2007; Bossert and Stern 2014; Marchant and Kaganovsky 2015). …”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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Rationale and objective In humans, exposure to contexts previously associated with heroin use can provoke relapse. In rats, exposure to heroin-paired contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. We previously demonstrated that the projections from ventral medial prefrontal cortex (vmPFC) to nucleus accumbens (NAc) shell play a role in this reinstatement. The ventral subiculum (vSub) sends glutamate projections to NAc shell and vmPFC. Here, we determined whether these projections contribute to context-induced reinstatement. Methods We trained rats to self-administer heroin (0.05–0.1 mg/kg/infusion) for 3 h per day for 12 days; drug infusions were paired with a discrete tone-light cue. Lever pressing in the presence of the discrete cue was subsequently extinguished in a different context. We then tested the rats for reinstatement in the heroin- and extinction-associated contexts under extinction conditions. We combined Fos with the retrograde tracer Fluoro-Gold (FG) to determine projection-specific activation during the context-induced reinstatement tests. We also used anatomical disconnection procedures to determine whether the vSub→NAc shell and vSub→vmPFC projections are functionally involved in this reinstatement. Results Exposure to the heroin but not the extinction context reinstated lever pressing. Context-induced reinstatement of heroin seeking was associated with increased Fos expression in vSub neurons, including those projecting to NAc shell and vmPFC. However, anatomical disconnection of the vSub→NAc shell projection, but not the vSub→vmPFC projection, decreased this reinstatement. Conclusions Our data indicate that the vSub→NAc shell glutamatergic projection, but not the vSub→vmPFC projection, contributes to context-induced reinstatement of heroin seeking.

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“…Results from several studies indicate a critical role of nucleus accumbens (NAc) core in context-induced relapse to alcohol seeking after either extinction or punishment. NAc core injections of muscimol+baclofen or the dopamine D1-family receptor antagonist SCH23390 decrease context-induced relapse to alcohol seeking after extinction, and NAc core SCH23390 injections decrease context-induced relapse after punishment (Chaudhri et al 2008 , 2010 ; Marchant and Kaganovsky 2015 ). It is currently unknown whether NAc core plays a similar role in context-induced relapse to cocaine seeking after punishment or extinction.…”

Section: Brain Mechanisms Of Context-induced Relapse After Extinctionmentioning

confidence: 99%

“…This model is a modified ABA renewal procedure in which abstinence is achieved in context B, despite alcohol availability, by punishment with response-contingent electric footshock. Using this model, we have demonstrated context-induced relapse to both alcohol and cocaine seeking when rats were tested in context A after punishment-imposed abstinence in context B (Marchant et al 2014 , 2016 ; Marchant and Kaganovsky 2015 ; Pelloux et al 2018a , b ). Our model and findings extend previous research in the addiction field on the use of punishment procedures to model the negative consequences of drug seeking and drug use (Deroche-Gamonet et al 2004 ; Marchant et al 2013b ; Panlilio et al 2003 ; Pelloux et al 2007 ; Vanderschuren et al 2017 ; Vanderschuren and Everitt 2004 ; Wolffgramm and Heyne 1995 ).…”

Section: Introductionmentioning

confidence: 99%

Context-induced relapse after extinction versus punishment: similarities and differences

et al. 2018

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Results from clinical studies suggest that drug relapse and craving are often provoked by exposure to drug-associated contexts. Since 2002, this phenomenon has been modeled in laboratory animals using the ABA renewal model. In the classical version of this model, rats with a history of drug self-administration in one context (A) undergo extinction in a different context (B) and reinstate (or relapse to) drug seeking after exposure to the original drug-associated context (A). In a more recent version of the model introduced in 2013, the experimental conditions in context A are identical to those used in the classical model, but drugreinforced responding in context B is suppressed by probabilistic punishment. The punishment-based ABA renewal model is proposed to resemble abstinence in humans, which is often initiated by the desire to avoid the negative consequences of drug use. The goal of our review is to discuss similarities and differences in mechanisms that play a role in suppression of drug seeking in context B and context-induced relapse to drug seeking in context A in the two models. We first describe psychological mechanisms that mediate extinction and punishment of drug-reinforced responding in context B. We then summarize recent findings on brain mechanisms of context-induced relapse of drug seeking after extinction, or punishment-imposed abstinence. These findings demonstrate both similarities and differences in brain mechanisms underlying relapse in the two variations of the ABA renewal model. We conclude by briefly discussing clinical implications of the preclinical studies.

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A critical role of nucleus accumbens dopamine D1-family receptors in renewal of alcohol seeking after punishment-imposed abstinence.

Cited by 33 publications

References 55 publications

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

Nucleus Accumbens Drd1-Expressing Neurons Control Aggression Self-Administration and Aggression Seeking in Mice

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

Context-induced relapse after extinction versus punishment: similarities and differences

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