NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

Hyman, Steven E.; Malenka, Robert C.; Nestler, Eric J.

doi:10.1146/annurev.neuro.29.051605.113009

Cited by 2,346 publications

(1,922 citation statements)

References 201 publications

Supporting

Mentioning

1,834

Contrasting

Unclassified

Order By: Relevance

“…However, when drugs of abuse are repeatedly used, behaviors related to sustaining the addiction may progressively supplant behaviors optimal for survival. This singleminded pursuit tends to undermine, rather than promote, species survival, effectively 'hijacking' the neural systems related to the pursuit of rewards (Hyman et al, 2006).…”

Section: Mesostriatal Acetylcholine and Reward Mediationmentioning

confidence: 99%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

163

138

View full text Add to dashboard Cite

Central nervous system cholinergic neurons arise from several discrete sources, project to multiple brain regions, and exert specific effects on reward, learning, and memory. These processes are critical for the development and persistence of addictive disorders. Although other neurotransmitters, including dopamine, glutamate, and serotonin, have been the primary focus of drug research to date, a growing preclinical literature reveals a critical role of acetylcholine (ACh) in the experience and progression of drug use. This review will present and integrate the findings regarding the role of ACh in drug dependence, with a primary focus on cocaine and the muscarinic ACh system. Mesostriatal ACh appears to mediate reinforcement through its effect on reward, satiation, and aversion, and chronic cocaine administration produces neuroadaptive changes in the striatum. ACh is further involved in the acquisition of conditional associations that underlie cocaine self-administration and context-dependent sensitization, the acquisition of associations in conditioned learning, and drug procurement through its effects on arousal and attention. Long-term cocaine use may induce neuronal alterations in the brain that affect the ACh system and impair executive function, possibly contributing to the disruptions in decision making that characterize this population. These primarily preclinical studies suggest that ACh exerts a myriad of effects on the addictive process and that persistent changes to the ACh system following chronic drug use may exacerbate the risk of relapse during recovery. Ultimately, ACh modulation may be a potential target for pharmacological treatment interventions in cocaine-addicted subjects. However, the complicated neurocircuitry of the cholinergic system, the multiple ACh receptor subtypes, the confluence of excitatory and inhibitory ACh inputs, and the unique properties of the striatal cholinergic interneurons suggest that a precise target of cholinergic manipulation will be required to impact substance use in the clinical population.

show abstract

Section: Mesostriatal Acetylcholine and Reward Mediationmentioning

confidence: 99%

The Role of Acetylcholine in Cocaine Addiction

Williams

Adinoff²

2007

Neuropsychopharmacol

163

138

View full text Add to dashboard Cite

show abstract

“…1991; Hyman et al. 2006; Krasnova and Cadet 2009). Rodent studies have demonstrated that DAT and VMAT2 play important roles in reinforcing behaviors (Hall et al.…”

Section: Introductionmentioning

confidence: 99%

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

et al. 2016

View full text Add to dashboard Cite

IntroductionThe dopaminergic (DA) system plays important roles in addiction. However, human DA neurons from drug‐dependent subjects were not available for study until recent development in inducible pluripotent stem cells (iPSCs) technology.MethodsIn this study, we produced DA neurons differentiated using iPSCs derived from opioid‐dependent and control subjects carrying different 3′ VNTR (variable number tandem repeat) polymorphism in the human dopamine transporter (DAT or SLC6A3). In addition, the effects of valproic acid (VPA) exposures on iPSC‐derived human DA neurons are also examined.ResultsWe present the first evidence suggesting that the 3′ VNTR polymorphism in the hDAT gene affects DAT expression level in iPSC‐derived human DA neurons. In human DA neurons, which provide an appropriate cellular milieu, VPA treatment alters the expression of several genes important for dopaminergic neuron function including DAT, Nurr1, and TH; this might partly explain its action in regulating addictive behaviors. VPA treatment also significantly increased DA D2 receptor (Drd2) expression, especially in the opioid‐dependent iPSC cell lines.ConclusionsOur data suggest that human iPSC‐derived DA neurons may be useful in in vitro experimental model to examine the effects of genetic variation in gene regulation, to examine the underlying mechanisms in neurological disorders including drug addiction, and to serve as a platform for therapeutic development.

show abstract

“…[1][2][3][4]. The vast number of clinical neuroimaging studies conducted on addicted individuals reveal striking abnormalities in prefrontal cortex (PFC) activity, relative to control subjects, that include reduced basal metabolic activity, reduced regional activation upon presentation of cues associated with non-drug primary reinforcers and enhanced metabolic activity upon presentation of drug-associated cues [e.g., [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

View full text Add to dashboard Cite

Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

show abstract

NEURAL MECHANISMS OF ADDICTION: The Role of Reward-Related Learning and Memory

Cited by 2,346 publications

References 201 publications

The Role of Acetylcholine in Cocaine Addiction

The Role of Acetylcholine in Cocaine Addiction

Using iPSC‐derived human DA neurons from opioid‐dependent subjects to study dopamine dynamics

Homers regulate drug-induced neuroplasticity: Implications for addiction

Contact Info

Product

Resources

About