Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala

Millan, E. Zayra; McNally, Gavan P.

doi:10.1101/lm.2144411

Cited by 43 publications

(33 citation statements)

References 44 publications

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“…Chaudhri et al (2013) reported that reversible inactivation of this projection decreases context-induced reinstatement of alcohol seeking. In contrast, Millan et al (2011) reported that inactivation of this projection increases reinstatement of alcoholic beer seeking.…”

Section: Discussionmentioning

confidence: 94%

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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Section: Discussionmentioning

confidence: 94%

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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“…Immediately before the first 2 days of punishment, rats received bilateral infusions of 0.9% phosphate-buffered saline or of the AMPA antagonist NBQX (1 µg/µl; Sigma-Aldrich, Sydney, Australia) to assess the role of LHb in the acquisition of punishment. This dose of NBQX is sufficient to prevent aversion-related signals exciting the LHb [16] and has also yielded behaviourally significant yet specific effects in previous experiments [17]. For microinjections, a 33-gauge microinjection cannula (Plastics One, Roanoke, VA, USA) was inserted into the guide cannula and connected to a 10 µl glass syringe (Hamilton Company, NV, USA) operated by an infusion pump (World Precision Instruments, FL, USA).…”

Section: Methodsmentioning

confidence: 99%

The Role of the Lateral Habenula in Punishment

Jean-Richard-dit-Bressel

McNally

2014

PLoS ONE

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The lateral habenula (LHb) is a small epithalamic structure that projects via the fasciculus retroflexus to the midbrain. The LHb is known to modulate midbrain dopamine (DA) neurons, including inhibition of ventral tegmental area (VTA) neurons via glutamatergic excitation of the GABAergic rostromedial tegmental nucleus (RMTg). A variety of lines of evidence show activity in LHb and the LHb-RMTg pathway is correlated with, and is sufficient to support, punishment learning. However, it is not immediately clear whether LHb is necessary for punishment. Here we used a within-subjects punishment task to assess the role of LHb in the acquisition and expression of punishment as well as in aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of an AMPA receptor antagonist (NBQX) into LHb had no effect on the acquisition or expression of this punishment, or on aversive choice, but did increase locomotion. Infusion of the sodium channel blocker bupivacaine likewise had no effect on expression of punishment. However, infusion of the calcium channel blocker mibefradil did affect expression of punishment by significantly decreasing the latency with which rats responded on the punished lever and significantly increasing unpunished lever-pressing. Taken together, these findings indicate that the LHb plays a limited role in punishment, influencing only latency to respond. This role is linked to calcium channel permeability and not AMPA receptor or sodium channel permeability.

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“…The role for caudal BLA in both punishment and extinction of instrumental responding could reflect this subregion's general role in suppression of appetitively motivated behavior. Given the caudal BLA-AcbSh pathway has been shown to mediate appetitive extinction expression (Millan and McNally 2011) and the role of PL in action-outcome contingency encoding (Cardinal et al 2003;Corbit and Balleine 2003), these structures could be considered strong candidates for mediating punishment. However, the role of the specific connectivity of caudal BLA (e.g., PL, AcbSh) in the acquisition and expression of punishment as well as aversive choice remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

The role of the basolateral amygdala in punishment

Jean-Richard-dit-Bressel

McNally

2015

Learn. Mem.

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Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects punishment task to assess the role of the BLA in the acquisition and expression of punishment as well as aversive choice. Rats that pressed two individually presented levers for pellet rewards rapidly suppressed responding to one lever if it also caused footshock deliveries (punished lever) but continued pressing a second lever that did not cause footshock (unpunished lever). Infusions of GABA agonists baclofen and muscimol (BM) into the BLA significantly impaired the acquisition of this suppression. BLA inactivations using BM also reduced the expression of well-trained punishment. There was anatomical segregation within the BLA so that caudal, not rostral, BLA was implicated in punishment. However, when presented with punished and unpunished levers simultaneously in a choice test without deliveries of shock punisher, rats expressed a preference for unpunished over the punished lever and BLA inactivations had no effect on this preference. Taken together, these findings indicate that the BLA is important for both the acquisition and expression of punishment but not for aversive choice. This role appears to be linked to neurons in the caudal BLA, rather than rostral BLA, although the circuitry that contributes to this functional segregation is currently unknown, and is most parsimoniously interpreted as a role for caudal BLA in determining the aversive value of the shock punisher.Aversive reinforcement, such as delivery of footshock, can have two distinct consequences for learning and behavior. First, it supports learning about its environmental antecedents to imbue such stimuli with the ability to elicit conditioned responses. In this way, animals learn to fear a stimulus that signals occurrence of footshock and will express species-typical defense reactions upon subsequent presentations of that stimulus. Second, aversive reinforcement supports learning about its behavioral antecedents and alters the probability that these behaviors will be emitted again in the future. In this way, animals learn to withhold or reduce a behavior that causes delivery of footshock. These two consequences of aversive reinforcement, fear and punishment, are linked to the actions of different learning processes. Fear is due to the operation of Pavlovian conditioning and formation of associations between the CS and the shock US. Punishment is due to the operation of instrumental aversive learning and the formation of an association between a response and the shock punisher (Bolles 1975;Bolles et al.

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Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala

Cited by 43 publications

References 44 publications

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

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

The Role of the Lateral Habenula in Punishment

The role of the basolateral amygdala in punishment

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