Reward loss and addiction: Opportunities for cross-pollination

Ortega, Leonardo A.; Solano, José L.; Torres, Carmen; Papini, Mauricio R.

doi:10.1016/j.pbb.2017.02.001

Cited by 31 publications

(10 citation statements)

References 226 publications

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“…The expressions of disorder emerging as consequences of exposure to reward loss have been neglected in approaches to the psychobiology of substance abuse disorders. This notion emphasizes the shared characteristics reward loss and addiction are reviewed, namely, the neural circuitry involved in reward devaluation, the influence of genetic and reward history on the behavioral vulnerability and resilience, the role of competing natural rewards, and emotional self-medication as a backdrop [ 11 ] to the consequences evolving in the “Reward Deficiency Syndrome”. The Reward Deficiency Syndrome, characterized by expressions of reward-seeking behavior and/or addictions and involving a G protein-coupled receptor located on postsynaptic dopaminergic neurons that is centrally involved in reward-mediating mesocorticolimbic pathways, originates from genetic variations, most notably resulting from those carrying the D2A1 allele implicated in addiction and abuse [ 12 , 13 ].…”

mentioning

confidence: 99%

Physical Exercise Interventions for Drug Addictive Disorder

Archer¹,

Badgaiyan²,

Blum³

2017

J Reward Defic Syndr Addict Sci

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mentioning

confidence: 99%

Physical Exercise Interventions for Drug Addictive Disorder

Archer¹,

Badgaiyan²,

Blum³

2017

J Reward Defic Syndr Addict Sci

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“…In this context, pharmacological compounds repressing striatopallidal activity appear as promising candidates for the treatment of OUD, possibly by restoring "liking" (121) for non-drug, notably social, stimuli. More broadly, opiate addiction sharing striking phenotypic and neurobiological features with other diseases considered as "reward deficiency syndromes", such as autism or depression (27,116,122,123), our work opens promising avenues towards the development of common therapeutic strategies for these pathologies. suppressed feeding test, chronic mGluR4 PAM administration normalized latency to feed and food intake in morphine abstinent animals since the lower dose (abstinence: F1,56=11.3, p<0.01; dose: F2,56=15.4, p<0.0001; abstinence x dose: F2,57=10.5, p<0.001), with no effect in vehicle or cocaine abstinent animals.…”

Section: Resultsmentioning

confidence: 92%

Facilitating mGluR4 activity reverses the long-term deleterious consequences of chronic morphine exposure

Becker

Pellissier

Corde

et al. 2020

Preprint

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AbstractBackgroundUnderstanding the neurobiological underpinnings of abstinence from drugs of abuse is critical to allow better recovery and ensure relapse prevention in addicted subjects.MethodsBy comparing the long-term transcriptional consequences of morphine and cocaine exposure, we identified the metabotropic glutamate receptor subtype 4 (mGluR4) as a promising pharmacological target in morphine abstinence. We evaluated the behavioral and molecular effects of facilitating mGluR4 activity in abstinent mice.ResultsTranscriptional regulation of marker genes of medium spiny neurons (MSNs) in the nucleus accumbens (NAc) allowed best discriminating between 4-week morphine and cocaine abstinence. Among these markers, Grm4, encoding mGluR4, displayed down-regulated expression in the caudate putamen and NAc of morphine, but not cocaine, abstinent mice. Remarkably, chronic administration of the mGluR4 positive allosteric modulator (PAM) VU0155041 (2.5 and 5 mg/kg) rescued social abilities, normalized stereotypies and anxiety and blunted locomotor sensitization in morphine abstinent mice. This treatment improved social preference but increased stereotypies in cocaine abstinent mice. Finally, the beneficial behavioral effects of VU0155041 treatment in morphine abstinent animals were correlated with restored expression of key MSN and neural activity marker genes in the NAc.ConclusionsThis study is the first report of relieving effects of a pharmacological treatment, chronic administration of the mGluR4 PAM VU0155041, on long-term deleterious consequences of morphine exposure. It illustrates the neurobiological differences between opiate and psychostimulant abstinence and points to pharmacological repression of excessive activity of D2-MSNs in the NAc as a promising therapeutic lever in drug addiction.

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“…In the current study, we expand this literature by observing cSNC effects caused by a reaction to loss of alcohol. This is of interest because cSNC effects have shared neurochemical and neurobiological underpinnings with addiction (for a review, see Ortega et al, 2017); for example, recent research has shown that inactivation of the central amygdala (CeA) prevents a cSNC effect following a sucrose downshift task (Guarino et al, 2020). These findings suggest that the CeA, a brain region also implicated in the development of AUD (for a review, see Roberto et al, 2020), is crucial for cSNC.…”

Section: Discussionmentioning

confidence: 99%

“…Both frontloading and cSNC have also been observed in HAP1 mice following an unexpected switch from an EtOH solution to a water solution (Linsenbardt and Boehm, 2015). This reaction to an unexpected loss of reward has recently become of great interest as a potential behavioral endophenotype for AUD (Ortega et al, 2017), and may be evidence of an important but understudied cognitive construct amenable to intervention.…”

mentioning

confidence: 95%

High Alcohol–Preferring Mice Show Reaction to Loss of Ethanol Reward Following Repeated Binge Drinking

Ardinger

Grahame

Lapish

et al. 2020

Alcoholism Clin & Exp Res

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Background Beyond yielding high blood ethanol (EtOH) concentrations (BECs), binge‐drinking models allow examination of drinking patterns which may be associated with EtOH’s rewarding effects, including front‐loading and consummatory successive negative contrast (cSNC), a decrease in intake when only water is available to subjects expecting EtOH. The goals of the current study were to broaden our understanding of these reward‐related behaviors during binge EtOH access in high alcohol–preferring (HAP) replicate lines (HAP2 and HAP3) of mice selectively bred to prefer alcohol. We hypothesized that both lines would show evidence of front‐loading during binge EtOH access and that we would find a cSNC effect in groups where EtOH was replaced with water, as these results have been shown previously in HAP1 mice. Methods HAP replicate 2 and replicate 3 female and male mice were given 2 hours of EtOH or water access in the home cage for 15 consecutive days using "drinking in the dark" (DID) procedures. Mice received the same fluid (either 20% unsweetened EtOH or water) for the first 14 days. However, on the 15th day, half of the mice from these 2 groups were provided with the opposite assigned fluid (EtOH groups received water and vice versa). Intake was measured in 1‐minute bins using specialized sipper tubes, which allowed within‐session analyses of binge‐drinking patterns. Results EtOH front‐loading was observed in both replicates. HAP3 mice displayed front‐loading on the first day of EtOH access, whereas front‐loading developed following alcohol experience in HAP2 mice, which may suggest differences in initial sensitivity to EtOH reward. Consummatory SNC, which manifests as lower water intake in mice expecting EtOH as compared to mice expecting water, was observed in both replicates. Conclusions These findings increase confidence that defined changes in home cage consummatory behavior are driven by the incentive value of EtOH. The presence of cSNC across HAP replicates indicates that this reaction to loss of reward is genetically mediated, which suggests that there is a biological mechanism that might be targeted.

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Reward loss and addiction: Opportunities for cross-pollination

Cited by 31 publications

References 226 publications

Physical Exercise Interventions for Drug Addictive Disorder

Physical Exercise Interventions for Drug Addictive Disorder

Facilitating mGluR4 activity reverses the long-term deleterious consequences of chronic morphine exposure

High Alcohol–Preferring Mice Show Reaction to Loss of Ethanol Reward Following Repeated Binge Drinking

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