Opioid receptor desensitization: mechanisms and its link to tolerance

Allouche, Stéphane; Noble, Florence; Marie, Nicolas

doi:10.3389/fphar.2014.00280

Cited by 124 publications

(102 citation statements)

References 202 publications

(360 reference statements)

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“…It not only displays a long-lasting opiate agonist profile, but also renders subsequent administration of heroin ineffectual (Allouche et al, 2014). As a consequence, we have proposed that a successful agonist therapy for cocaine addiction must have two basic properties, to wit: (1) a slow-onset long-lasting DAT inhibitor profile, to satisfy drug hunger, and (2) the ability to block subsequent cocaine action (Peng et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction

Song²,

et al. 2016

Neuropsychopharmacol

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Agonist-replacement therapies have been successfully used for treatment of opiate and nicotine addiction, but not for cocaine addiction. One of the major obstacles is the cocaine-like addictive potential of the agonists themselves. We report here an atypical dopamine (DA) transporter (DAT) inhibitor, CTDP-32476, that may have translational potential for treating cocaine addiction. In vitro ligand-binding assays suggest that CTDP-32476 is a potent and selective DAT inhibitor and a competitive inhibitor of cocaine binding to the DAT. Systemic administration of CTDP-32476 alone produced a slow-onset, long-lasting increase in extracellular nucleus accumbens DA, locomotion, and brain-stimulation reward. Drug-naive rats did not self-administer CTDP-32476. In a substitution test, cocaine self-administration rats displayed a progressive reduction in CTDP-32476 self-administration with an extinction pattern of drug-taking behavior, suggesting significantly lower addictive potential than cocaine. Pretreatment with CTDP-32476 inhibited cocaine self-administration, cocaineassociated cue-induced relapse to drug seeking, and cocaine-enhanced extracellular DA in the nucleus accumbens. These findings suggest that CTDP-32476 is a unique DAT inhibitor that not only could satisfy 'drug hunger' through its slow-onset long-lasting DAT inhibitor action, but also render subsequent administration of cocaine ineffectual-thus constituting a novel and unique compound with translational potential as an agonist therapy for treatment of cocaine addiction.

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Section: Introductionmentioning

confidence: 99%

CTDP-32476: A Promising Agonist Therapy for Treatment of Cocaine Addiction

Song²,

et al. 2016

Neuropsychopharmacol

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“…Desensitization and Internalization in Opioid Tolerance and Dependence. Development of opioid tolerance is partly dependent on a partial loss of capacity of the m receptor to signal to its intracellular effectors (Kieffer and Evans, 2002;Christie, 2008;Allouche et al, 2014). This "receptor tolerance" can be achieved by different mechanisms, primarily by decreased cell surface expression of m receptors and/or attenuation of coupling efficacy of the surface receptors.…”

Section: G Opioid-induced Neural Adaptationsmentioning

confidence: 99%

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

Korpi¹,

Hollander²,

Farooq

et al. 2015

Pharmacol Rev

124

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“…There are several mechanisms responsible for the development of opioid tolerance. These mechanisms might involve receptor desensitization, internalization, second messenger switch, receptor dimerization, changes in the endogenous opioid system and neuronal network functions, etc (Allouche et al, 2014;Crain and Shen, 1996;George et al, 2000;He and Lee, 1997;Jordan and Devi, 1999;Kiraly et al, 2006;Lee et al, 1980;Riba et al, 2002;Szentirmay et al, 2013;Tulunay et al, 1981).…”

Section: Introductionmentioning

confidence: 95%