Toward an evolutionary basis for resilience to drug addiction

Ahmed, Serge H.

doi:10.1017/s0140525x11000677

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…The validity of our computational model was tested on raw SA data obtained from experiments conducted by Serge Ahmed and his coworkers. Hence, although in this work we focused primarily on results and literature generated by Ahmed and colleagues, the escalation of drug intake with the long-access model has also been observed in many other laboratories (Ahmed, 2011, 2012). We should however mention that there are also experiments that did not report escalation of intake with this model.…”

Section: Discussionmentioning

confidence: 93%

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Cocaine addiction as a homeostatic reinforcement learning disorder.

Keramati¹,

Durand²,

Girardeau³

et al. 2017

Psychological Review

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Drug addiction implicates both reward learning and homeostatic regulation mechanisms of the brain. This has stimulated 2 partially successful theoretical perspectives on addiction. Many important aspects of addiction, however, remain to be explained within a single, unified framework that integrates the 2 mechanisms. Building upon a recently developed homeostatic reinforcement learning theory, the authors focus on a key transition stage of addiction that is well modeled in animals, escalation of drug use, and propose a computational theory of cocaine addiction where cocaine reinforces behavior due to its rapid homeostatic corrective effect, whereas its chronic use induces slow and long-lasting changes in homeostatic setpoint. Simulations show that our new theory accounts for key behavioral and neurobiological features of addiction, most notably, escalation of cocaine use, drug-primed craving and relapse, individual differences underlying dose-response curves, and dopamine D2-receptor downregulation in addicts. The theory also generates unique predictions about cocaine self-administration behavior in rats that are confirmed by new experimental results. Viewing addiction as a homeostatic reinforcement learning disorder coherently explains many behavioral and neurobiological aspects of the transition to cocaine addiction, and suggests a new perspective toward understanding addiction. (PsycINFO Database Record

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Section: Discussionmentioning

confidence: 93%

“…We should however mention that there are also experiments that did not report escalation of intake with this model. Yet, as far as we can judge from the published literature, they represent a small minority of cases (reviewed in Ahmed, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cocaine addiction as a homeostatic reinforcement learning disorder.

Keramati¹,

Durand²,

Girardeau³

et al. 2017

Psychological Review

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“…Such oral consummatory cues are also present with the ingestion of saccharin by rats but are absent when nicotine is delivered intravenously. Finally, the properties of tobacco as a cognitive enhancer and as an appetite suppressant are likely to further contribute to its ongoing use in humans (Warburton ; Ahmed ), especially in environmental contexts where these non‐hedonic effects of nicotine are adaptive (Caprioli et al . ).…”

Section: Discussionmentioning

confidence: 99%

Rats quit nicotine for a sweet reward following an extensive history of nicotine use

et al. 2015

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Drug use may be exacerbated in environments which lack alternative means of engaging in rewarding behaviour. When alternative rewards are available, drug use may decrease-an effect that can be harnessed for therapeutic benefit. This idea is particularly well-supported by recent preclinical evidence demonstrating that a majority of rats will readily choose a potent non-drug reward over cocaine or heroin. Here we examine whether the same holds true for nicotine, a drug considered to have one of the highest addiction liabilities amongst drugs of abuse. Rats were trained to nose-poke separately for saccharin or nicotine on alternate days. Using a discrete-trial, forced-choice procedure, rats were then allowed to choose between nicotine and saccharin. This was followed by choice testing after a decrease in saccharin concentration (0.2-0%), omission of the fluid reward, an increase in nicotine concentration and following an extended nicotine self-administration history. All rats demonstrated a clear and immediate preference for saccharin at all times. This was despite variations in reward concentrations, or after an extensive nicotine history. Notably, rats preferred to nose-poke for water over nicotine and would omit responses when no fluid was delivered, rather than resume responding for nicotine. Overall, this study confirms and extends to nicotine previous research on other drugs of abuse, including cocaine and heroin. The ease with which rats quit nicotine in the present study contrasts with the well-known difficulty of humans to quit tobacco smoking. Possible factors that could explain this apparent discrepancy are discussed.

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“…Alcohol addiction is a very common psychiatric disorder with severe health consequences for the individual and detrimental effects for social environment and society. 1 The molecular mechanisms that lead to addiction and those that prevent chronic consumers from such a transition 2 , 3 are not sufficiently understood. 4 Although symptoms of alcoholism are very similar among affected individuals and well classified in current diagnostic manuals, there are different pathways, which lead from a controlled consumption, which is an accepted part of western society culture, 2 , 5 to alcohol addiction.…”

Section: Introductionmentioning

confidence: 99%

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction

et al. 2017

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In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show a high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in the control of alcohol addiction-associated behaviours. EFhd2 knockout (KO) mice drink more alcohol than controls and spontaneously escalate their consumption. This coincided with a sensation-seeking and low-anxiety phenotype. A reversal of the behavioural phenotype with β-carboline, an anxiogenic inverse benzodiazepine receptor agonist, normalized alcohol preference in EFhd2 KO mice, demonstrating an EFhd2-driven relationship between personality traits and alcohol preference. These findings were confirmed in a human sample where we observed a positive association of the EFhd2 single-nucleotide polymorphism rs112146896 with lifetime drinking and a negative association with anxiety in healthy adolescents. The lack of EFhd2 reduced extracellular dopamine levels in the brain, but enhanced responses to alcohol. In confirmation, gene expression analysis revealed reduced tyrosine hydroxylase expression and the regulation of genes involved in cortex development, Eomes and Pax6, in EFhd2 KO cortices. These findings were corroborated in Xenopus tadpoles by EFhd2 knockdown. Magnetic resonance imaging (MRI) in mice showed that a lack of EFhd2 reduces cortical volume in adults. Moreover, human MRI confirmed the negative association between lifetime alcohol drinking and superior frontal gyrus volume. We propose that EFhd2 is a conserved resilience factor against alcohol consumption and its escalation, working through Pax6/Eomes. Reduced EFhd2 function induces high-risk personality traits of sensation-seeking/low anxiety associated with enhanced alcohol consumption, which may be related to cortex function.

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Toward an evolutionary basis for resilience to drug addiction

Cited by 10 publications

References 22 publications

Cocaine addiction as a homeostatic reinforcement learning disorder.

Cocaine addiction as a homeostatic reinforcement learning disorder.

Rats quit nicotine for a sweet reward following an extensive history of nicotine use

EFhd2/Swiprosin-1 is a common genetic determinator for sensation-seeking/low anxiety and alcohol addiction

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