Dopamine and addiction: what have we learned from 40 years of research

Solinas, Marcello; Belujon, Pauline; Fernagut, Pierre‐Olivier; Jaber, Mohamed; Thiriet, Nathalie

doi:10.1007/s00702-018-1957-2

Cited by 102 publications

(89 citation statements)

References 519 publications

(628 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Although dopamine strongly contributes to the reinforcing properties of all drugs of abuse including opioids [reviewed in (31)], a robust literature implicates dysregulated homeostasis at glutamatergic synapses in OUD-associated cognitive impairments and cue reactivity (i.e., craving) (32,33). For example, glutamate levels measured by magnetic resonance spectroscopy in reward-associated brain regions in opioid-dependent users correlate positively with measures of impulsivity (34), and opioid-conditioned cues evoke craving in parallel with functional magnetic resonance imaging measures of increased activity in corticostriatal and amygdalostriatal glutamatergic circuits (35).…”

Section: Preclinical Models Of Opioid Addictionmentioning

confidence: 99%

The Opioid-Addicted Tetrapartite Synapse

Kruyer¹,

Chioma²,

Kalivas

2020

Biological Psychiatry

View full text Add to dashboard Cite

Opioid administration in preclinical models induces long-lasting adaptations in reward and habit circuitry. The latest research demonstrates that in the nucleus accumbens, opioid-induced excitatory synaptic plasticity involves presynaptic and postsynaptic elements as well as adjacent astroglial processes and the perisynaptic extracellular matrix. We outline opioid-induced modifications within each component of the tetrapartite synapse and provide a neurobiological perspective on how these adaptations converge to produce addiction-related behaviors in rodent models. By incorporating changes observed at each of the excitatory synaptic compartments into a unified framework of opioid-induced glutamate dysregulation, we highlight new avenues for restoring synaptic homeostasis that might limit opioid craving and relapse vulnerability.

show abstract

Section: Preclinical Models Of Opioid Addictionmentioning

confidence: 99%

The Opioid-Addicted Tetrapartite Synapse

Kruyer¹,

Chioma²,

Kalivas

2020

Biological Psychiatry

View full text Add to dashboard Cite

show abstract

“…5k), suggesting that stimulation of the PrL-PVT pathway in STs decreases DA in the NAc shell (p=0.153, Cohen's d=1. 26).…”

Section: Stimulation Of the Prl-pvt Pathway Does Not Affect The Attrimentioning

confidence: 99%

“…Notably, the mesocorticolimbic dopamine system, which plays a major role in the attribution of incentive salience to reward-cues [21][22][23] , has been implicated in all of these disorders 18,[24][25][26][27] .…”

Section: Introductionmentioning

confidence: 99%

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

Campus

Covelo

Kim

et al. 2019

Preprint

View full text Add to dashboard Cite

Stimuli or cues in the environment can elicit complex emotional states, and thereby maladaptive behavior, as a function of their ascribed value. Here we capture individual variation in the propensity to attribute motivational value to reward-cues using the signtracker/goal-tracker animal model. Goal-trackers attribute predictive value to rewardcues, and sign-trackers attribute both predictive and incentive value. Using chemogenetics and microdialysis, we show that, in sign-trackers, stimulation of the neuronal pathway from the prelimbic cortex (PrL) to the paraventricular nucleus of the thalamus (PVT) decreases the incentive value of a reward-cue. In contrast, in goaltrackers, inhibition of the PrL-PVT pathway increases both the incentive value and dopamine levels in the nucleus accumbens shell. The PrL-PVT pathway, therefore, exerts top-down control over the dopamine-dependent process of incentive salience attribution. These results highlight PrL-PVT pathway as a potential target for treating psychopathologies associated with the attribution of excessive incentive value to reward-cues, including addiction. independent delivery of food-US, distinct conditioned responses emerge. Some rats, goal-trackers (GTs), approach the location of impending food delivery upon the lever-CS presentation, while others, sign-trackers (STs), approach and interact with the lever-CS itself. For both GTs and STs the lever-CS acquires predictive value and elicits a conditioned response, but for STs, the CS also acquires incentive value. This animal model, therefore, provides a unique platform to investigate the neurobiological determinants of individual differences in the propensity to attribute incentive salience to reward-cues.Previous studies suggest that sign-tracking behavior results from enhanced activity in subcortical brain circuits known to mediate motivated behaviors, including the striatal dopamine system, the amygdala, and the hypothalamus 22,23,28-31 . In addition, relative to GTs, STs appear to have deficits in top-down cognitive control originating in the prefrontal cortex 32 . Thus, we hypothesize that sign-tracking behavior arises from an imbalance between top-down cognitive control and bottom-up motivational processes.One brain region that is ideally situated to act as a fulcrum between cortical, limbic and homeostatic circuits is the paraventricular nucleus of the thalamus (PVT). The PVT has, in fact, come to be known as the "thalamic gateway" 33 for appetitive motivation; acting to integrate cognitive, emotional, motivational and viscerosensitive information, and, in turn, guide behavioral responses 33,34 . Consistent with this view, the PVT has been implicated in the propensity to attribute incentive motivational value to reward-cues [35][36][37] .The functional connectivity of the PVT in response to cue-induced neuronal activity differentiates STs from GTs 28,29,35 . In STs, cue-induced activity in the PVT is correlated with activity in subcortical areas, including the nucleus accumbens (NAc); whereas in GTs, cue-...

show abstract

“…Finally, previous drug experiences were not equally distributed among DAT1 rs11133767 genotype groups, and effects might slightly depend on previous substance use experiences. Because of the involvement of DA in addiction, subjects carrying a TT genotype may be more prone to illicit substance use (65). Apart from this finding, given that our cohort included mostly drug-naive subjects with limited drug use experience, some alleles associated with increased drug use might even be underrepresented.…”

Section: Discussionmentioning

confidence: 99%

No Influence of Dopamine System Gene Variations on Acute Effects of MDMA

Vizeli

Liechti

2019

Front. Psychiatry

View full text Add to dashboard Cite

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a recreational substance also investigated as medication for posttraumatic stress disorder. Dopamine (DA) system stimulation likely contributes to the acute mood effects of amphetamines, including MDMA. Genetic variants, such as single-nucleotide polymorphisms (SNPs), and polymorphic regions of the DA system genes may in part explain interindividual differences in the acute responses to MDMA in humans. We characterized the effects of common genetic variants within genes coding for key players in the DA system including the dopamine D2 receptor (DRD2/ANKK1 rs1800497, DRD2 rs6277, and rs107959), the dopamine transporter (DAT1 rs28363170, rs3836790, rs6347, rs11133767, rs11564774, rs460000, and rs463379), and dopamine D4 receptor [DRD4, variable-number tandem repeat (VNTR)] on the subjective and autonomic response to MDMA (125 mg) in pooled data from randomized, placebo-controlled, crossover studies in a total of 149 healthy subjects. Plasma concentrations of MDMA were used as covariate in the analysis to control for individual pharmacokinetic (metabolic and weight) differences. None of the tested genetic polymorphisms within the DA system altered effects of MDMA when adjusting for multiple comparisons. Genetic variations in genes coding for players of the DA system are unlikely to explain interindividual variations in the acute effects of MDMA in humans.

show abstract

Dopamine and addiction: what have we learned from 40 years of research

Cited by 102 publications

References 519 publications

The Opioid-Addicted Tetrapartite Synapse

The Opioid-Addicted Tetrapartite Synapse

The Paraventricular Thalamus is a Critical Mediator of Top-down Control of Cue-motivated Behavior in Rats

No Influence of Dopamine System Gene Variations on Acute Effects of MDMA

Contact Info

Product

Resources

About