The neural encoding of cocaine-induced devaluation in the ventral pallidum

Chan, Chung-Lung; Wheeler, Daniel S.; Wheeler, Robert

doi:10.1016/j.nlm.2016.02.013

Cited by 6 publications

(7 citation statements)

References 36 publications

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“…The present results, along with previous work from our lab and others', indicate that Ox1R antagonism has potential as a pharmacological strategy for the treatment of opioid abuse, and provide new insights into the corresponding neural substrates. Importantly, the current study focused on the posterior VP, but VP is a heterogeneous structure with differences in cell morphology and connectivity patterns along the rostral-caudal axis, as well as different functional roles in reward-related behavior (Chan et al, 2016;Mahler et al, 2014b;Root et al, 2015;Smith et al, 2005). Future research should analyze roles for rostral VP in opiate addiction, as well as whether specific orexin neuronal populations or their targets regulate different aspects of opioid motivation.…”

Section: Discussionmentioning

confidence: 97%

Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil

Mohammdkhani

Pantazis

Bowrey

et al. 2018

Preprint

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1Signaling at the orexin-1 receptor (Ox1R) is important for motivation for various drugs of abuse. 2 Recently, our laboratory showed that systemic blockade of Ox1Rs decreased motivation for the 3 potent and short-acting opioid remifentanil, as well as remifentanil consumption at null cost 4 (Porter-Stransky et al., 2017). However, the central site(s) through which orexin acts to regulate 5 opioid-seeking behaviors are not known. We investigated ventral pallidum (VP) as a potential 6 site of orexin action, as VP is a known mediator of opioid reward and is densely innervated by 7 orexin-immunoreactive fibers. We used a within-session behavioral economics (BE) paradigm in 8 which remifentanil price (responses/µg iv remifentanil) was sequentially increased throughout 9 the session. Rats were implanted with bilateral cannulae into caudal VP (cVP), through which 10 microinjections of SB334867 (SB), an Ox1R antagonist, were given prior to BE and 11 reinstatement testing. Contrary to systemic SB treatment, intra-cVP SB preferentially reduced 12 motivation (increased demand elasticity and reinstatement) for reminfentanil, without affecting 13 remifentanil consumption at null cost. These effects were specific to cVP, as control 14 microinjections of SB immediately dorsal to cVP did not affect remifentanil-seeking. Baseline 15 demand for remifentanil predicted cued reinstatement of remifentanil seeking and the efficacy 16 with which intra-cVP SB administration reduced motivation for remifentanil. These findings 17 indicate a specific role for cVP Ox1R signaling in mediating the motivational properties of the 18 opioid remifentanil, distinct from its consumption at null cost. Our findings also highlight the BE 19 paradigm as an effective biomarker for predicting opioid addiction behaviors and treatment 20 efficacy. 21 22 Introduction: 33 In recent years, abuse of prescription opioids has risen rapidly and has become a major health 34 issue (Compton and Volkow, 2006; Lewis et al., 2017; Volkow and Collins, 2017; Dobbs and 35 Fogger, 2018). Thus, it is urgent to understand the neurobiological and behavioral mechanisms 36 underlying opioid addiction to facilitate development of new treatments for this disorder. The 37 hypothalamic orexin (hypocretin) system is a key modulator of drug seeking behaviors across a 38 variety of drugs of abuse, including opioids (Harris et al., 2005; Mahler et al., 2014a; Baimel et 39 al., 2015; James et al., 2017). Orexin-containing neurons are located in hypothalamus and project 40 widely throughout the brain, targeting two G-protein-coupled receptors (orexin receptors 1 and 41 2; Ox1R and Ox2R, respectively). In particular, signaling at Ox1R has been shown to mediate 42 motivation and addiction (for review, James et al., 2018). We found that blocking Ox1Rs can 43 disrupt opioid seeking behaviors: systemic blockade of Ox1R signaling reduced breakpoints for 44 heroin in a progressive ratio task (Smith and Aston-Jones, 2012) and attenuated demand 45 (motivation) for remifentanil in a behavioral e...

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Section: Discussionmentioning

confidence: 97%

Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil

Mohammdkhani

Pantazis

Bowrey

et al. 2018

Preprint

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“…We found the glutamate neurons concentrated in the VPvm and in sections rostral to the midline crossing of the anterior commissure. Thus, previous studies employing anatomical approaches to target rostral versus caudal VP may have enriched for or against, respectively, VP glutamate neurons 25 , 26 . Indeed, the density of glutamate neurons may relate to the ability of caudal but not rostral VP manipulations to trigger place preference, blunt cocaine-induced reinstatement, or modulate “liking” reactions and consummatory behavior 12 , 27 – 29 .…”

Section: Discussionmentioning

confidence: 99%

“…At the functional level, VPvm and VPdl neurons show distinctive response characteristics during cocaine self-administration 24 . Electrophysiological characteristics also differ depending on their rostro-caudal localization 25 , 26 , and pharmacological manipulation of the rostral (RVP) or caudal (CVP) VP induce different behavioral responses. For example, SP microinjection in the caudal but not rostral VP elicited conditioned place preference (CPP) 27 .…”

Section: Introductionmentioning

confidence: 99%

Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum

et al. 2018

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The ventral pallidum (VP) lies at the interface between sensory, motor, and cognitive processing—with a particular role in mounting behavioral responses to rewards. Though the VP is predominantly GABAergic, glutamate neurons were recently identified, though their relative abundances and respective roles are unknown. Here, we show that VP glutamate neurons are concentrated in the rostral ventromedial VP and project to qualitatively similar targets as do VP GABA neurons. At the functional level, we used optogenetics to show that activity in VP GABA neurons can drive positive reinforcement, particularly through projections to the ventral tegmental area (VTA). On the other hand, activation of VP glutamate neurons leads to behavioral avoidance, particularly through projections to the lateral habenula. These findings highlight cell-type and projection-target specific roles for VP neurons in behavioral reinforcement, dysregulation of which could contribute to the emergence of negative symptoms associated with drug addiction and other neuropsychiatric disease.

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“…We should note that VP activity both encodes and contributes to the likelihood of behavioral responses following the Pavlovian cue, though this encoding is weaker than in the instrumental task. VP activity may contribute to response likelihood in the Pavlovian task via the same underlying circuits and processes as in the instrumental task, or through distinct neural and psychological mechanisms, such as thencoding of incentive value versus expected reward value ( Chan et al, 2016 ; Tindell et al, 2009 ), as some evidence suggests that reward value and motivation rely on dissociable neural mechanisms even within VP ( Creed et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Ventral pallidal encoding of reward-seeking behavior depends on the underlying associative structure

Stout

Acs

et al. 2018

eLife

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Despite its being historically conceptualized as a motor expression site, emerging evidence suggests the ventral pallidum (VP) plays a more active role in integrating information to generate motivation. Here, we investigated whether rat VP cue responses would encode and contribute similarly to the vigor of reward-seeking behaviors trained under Pavlovian versus instrumental contingencies, when these behavioral responses consist of superficially similar locomotor response patterns but may reflect distinct underlying decision-making processes. We find that cue-elicited activity in many VP neurons predicts the latency of instrumental reward seeking, but not of Pavlovian response latency. Further, disruption of VP signaling increases the latency of instrumental but not Pavlovian reward seeking. This suggests that VP encoding of and contributions to response vigor are specific to the ability of incentive cues to invigorate reward-seeking behaviors upon which reward delivery is contingent.

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The neural encoding of cocaine-induced devaluation in the ventral pallidum

Cited by 6 publications

References 36 publications

Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil

Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil

Opponent control of behavioral reinforcement by inhibitory and excitatory projections from the ventral pallidum

Ventral pallidal encoding of reward-seeking behavior depends on the underlying associative structure

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