Diminished Role for Dopamine D1 Receptors in Cocaine Addiction?

Self, David W.

doi:10.1016/j.biopsych.2014.04.006

Cited by 11 publications

(11 citation statements)

References 10 publications

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“…Within this admittedly preliminary model, escalation of cocaine self-administration may result from a chronic decrease in NAc D1R neuronal activity. Animals would increase cocaine intake to maintain NAc dopamine at a higher level than prior to escalation (Serge H Ahmed et al, 2003) in an attempt to compensate for a decrease in NAc D1R neuronal activity (Serge H Ahmed & Koob, 2004;Doyle et al, 2014;Self, 2014). Basal decrease in NAc neuronal activity has been observed after both escalation and post-abstinence re-escalation of cocaine self-administration, particularly in the NAc shell subdivision (Guillem, Ahmed, & Peoples, 2014).…”

Section: Neural Substratesmentioning

confidence: 99%

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: Neural Substratesmentioning

confidence: 99%

Cocaine addiction as a homeostatic reinforcement learning disorder.

Keramati¹,

Durand²,

Girardeau³

et al. 2017

Psychological Review

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“…Compared to RLAs, RHAs display also a lower density of D2/3R in the striatum (Tournier et al, 2013), a characteristic that might underlie a higher vulnerability to cocaine addiction (Dalley et al, 2007). Interestingly, D2/3R have been shown to play an important role in relapse (De Vries, Schoffelmeer, Binnekade, & Vanderschuren, 1999; Gál & Gyertyán, 2006; Self, 2014), and their stimulation alone is sufficient to induce drug-seeking behavior in abstinent rats (De Vries et al, 2002; De Vries et al, 1999). However, it is not fully clear what the respective role of D2R and D3R is in relapse.…”

mentioning

confidence: 99%

Differential involvement of D2 and D3 receptors during reinstatement of cocaine-seeking behavior in the Roman high- and low-avoidance rats.

Dimiziani¹,

Añó²,

Tsartsalis³

et al. 2019

Behavioral Neuroscience

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Roman high- (RHA) and low-avoidance (RLA) rats have been used as a model for drug-addiction, showing, respectively, high- and low-responding to psychostimulants, and low versus high dopamine D2/3 receptors (D2/3R) striatal density. Previous studies indicated a major involvement of D2/3R on reinstatement of cocaine seeking, although the respective role of the two receptor subtypes is not clear. Here, we investigated sensitivity to cocaine self-administration (SA) through a dose-response protocol in RHAs and RLAs, and reinstatement of drug-seeking behavior at 15 days and 5 weeks following withdrawal. Compared to RLAs, RHAs confirmed a higher vulnerability to cocaine SA that was not related to a difference in sensitivity to the drug, as highlighted by the dose-response analysis. Both at early and late withdrawal, RHAs showed higher susceptibility than RLAs to reinstatement of drug-seeking when cocaine was used as a primer, but the two sublines did not differ when primed with the D2/3R agonist quinpirole. Moreover, while the specific D2R antagonist L741,626 blocked, the specific D3R antagonist SB-277011A failed to impair cocaine-primed relapse. The higher vulnerability of RHA versus RLA rats to cocaine-primed relapse, which contrasts with their similar vulnerability to quinpirole-primed relapse, suggests that the different propensity of both sublines to relapse likely relies on presynaptic rather than postsynaptic mechanisms. Moreover, our study challenges the involvement of D3R in the mechanisms underlying relapse to cocaine addiction, at least in conditions that may involve high levels of dopaminergic stimulation, and supports a major role of postsynaptic D2R over D3R in the vulnerability to relapse.

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“…In this context, the enhancement of D 1 receptor expression in the PCx shown here could contribute to a sustained therapeutic action following long-term MPH treatment (Mehta et al, 2000). The potential beneficial action of enhanced D 1 function in the VS is however questionable, as D 1 receptor activation in this part of the brain is known to stimulate reward-related behaviour following psychostimulant administration and could as such influence/promote drug-seeking behaviour M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT (Self, 2014). Moreover, the finding of this study that MPH-induced elevation of protein targets for catecholamine function was particularly marked in VS and PCx, two brain areas implicated in arousal and attention is supportive of the "arousal theory of ADHD" (Gutierrez et al, 2011).…”

Section: Accepted Manuscriptmentioning

confidence: 88%