Modulation of the endocannabinoid system: Therapeutic potential against cocaine dependence

Tanda, Gianluigi

doi:10.1016/j.phrs.2007.09.001

Cited by 19 publications

(17 citation statements)

References 156 publications

(192 reference statements)

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“…Further, a preliminary report indicated that RTI-371 blocked cocaine-induced locomotor stimulation (Navarro et al, 2009). Finally, because both RTI-371 and JHW007 produced positive-allosteric modulation of CB1Rs, and CB1Rs have been implicated in the neurobiology of cocaine addiction (see Tanda, 2007 for review), Navarro et al (2009) suggested that the atypical effects of both of these compounds were a result of a positive allosteric modulation of CB1Rs, as indicated by the increased efficacy of the CB1 agonist, CP 55940 in a calcium mobilization assay. From those results Navarro et al suggested that enhanced endocannabinoid neurotransmission may contribute to the cocaine-antagonist effects observed with these atypical DAT inhibitors.…”

Section: Effects Of Atypical Dat Inhibitorsmentioning

confidence: 99%

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Reith

Blough

Hong

et al. 2015

Drug and Alcohol Dependence

119

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Background Treatment of Stimulant-Use Disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies. Methods This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, either in vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal-chemical perspective. Results Possible mechanisms for atypicality at the molecular level can be deduced from the conformational cycle for substrate translocation. For each conformation, a crystal structure of a bacterial homolog is available, with a possible role of cholesterol, which is also present in the crystal of drosophila DAT. Although there is a direct relationship between behavioral potencies of most DAT inhibitors and their DAT affinities, a number of compounds bind to the DAT and inhibit dopamine uptake but do not share cocaine-like effects. Such atypical behavior, depending on the compound, may be related to slow DAT association, combined sigma-receptor actions, or bias for cytosol-facing DAT. Some structures are sterically small enough to serve as DAT substrates but large enough to also inhibit transport. Such compounds may display partial DA releasing effects, and may be combined with release or uptake inhibition at other monoamine transporters. Conclusions Mechanisms of atypical DAT inhibitors may serve as targets for the development of treatments for stimulant abuse. These mechanisms are novel and their further exploration may produce compounds with unique therapeutic potential as treatments for stimulant abuse.

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Section: Effects Of Atypical Dat Inhibitorsmentioning

confidence: 99%

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Reith

Blough

Hong

et al. 2015

Drug and Alcohol Dependence

119

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“…Indeed, the extant literature on treatment for psychostimulant drug abuse is expansive, and includes cognitive/behavioral therapy (e.g., for reviews, see Knapp et al, 2007;Shearer, 2007) and pharmacotherapies (e.g., for reviews, see Bubar and Cunningham, 2006;Dwoskin et al, 2006;Lile, 2006;Tanda, 2007, Withers et al, 1995. The latter of which include antidepressants (Dwoskin et al, 2006), serotonin modulation (Bubar and Cunningham, 2006), and endocannabinoid modulation (Tanda, 2007), to name a few. One may theorize that cessation of psychostimulant drug abuse would be beneficial for the HIV-infected population; so in essence, may serve as an intervention in the progression of HIV-related symptomatology.…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: Current status of dopamine system vulnerability in NeuroAIDS

Ferris

Mactutus

Booze

2008

Neuroscience & Biobehavioral Reviews

118

131

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There are roughly 30 to 40 million HIV infected individuals in the world as of December 2007, and drug abuse directly contributes to one-third of all HIV-infections in the United States. Antiretroviral therapy has increased the lifespan of HIV-seropositives, but CNS function often remains diminished, effectively decreasing quality of life. A modest proportion may develop HIV-associated dementia, the severity and progression of which is increased with drug abuse. HIV and drugs of abuse in the CNS target subcortical brain structures and DA systems in particular. This toxicity is mediated by a number of neurotoxic mechanisms, including but not limited to, aberrant immune response and oxidative stress. Therefore, novel therapeutic strategies must be developed that can address a wide variety of disparate neurotoxic mechanisms and apoptotic cascades. This paper reviews the research pertaining to the where, what, and how of HIV and cocaine/methamphetamine toxicity in the CNS. Specifically, where these toxins most affect the brain, what aspects of the virus are neurotoxic, and how these toxins mediate neurotoxicity.

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“…In addition to its well-known role in stress and anxiety 128 , the eCB system has been implicated in addiction-related processes and behaviors 129 . In fact, drugs of abuse and natural rewards are known to alter brain eCB content 130 .…”

Section: What Are the Molecular Mediators Of Addiction Pathology?mentioning

confidence: 99%

Biological substrates of addiction

Joffe

Grueter

2014

WIRES Cognitive Science

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This review is an introduction to addiction, the reward circuitry, and laboratory addiction models. Addiction is a chronic disease hallmarked by a state of compulsive drug seeking that persists despite negative consequences. Most of the advances in addiction research have centered on the canonical and contemporary drugs of abuse, however, addictions to other activities and stimuli also exist. Substances of abuse have the potential to induce long-lasting changes in the brain at the behavioral, circuit and synaptic levels. Addiction-related behavioral changes involve initiation, escalation and obsession to drug seeking and much of the current research is focused on mapping these manifestations to specific neural pathways. Drug abuse is well known to recruit components of the mesolimbic dopamine system, including the nucleus accumbens and ventral tegmental area. In addition, altered function of a wide variety of brain regions is tightly associated with specific manifestations of drug abuse. These regions peripheral to the mesolimbic pathway likely play a role in specific observed comorbidities and endophenotypes that can facilitate, or be caused by, substance abuse. Alterations in synaptic structure, function and connectivity, as well as epigenetic and genetic mechanisms are thought to underlie the pathologies of addiction. In preclinical models, these persistent changes are studied at the levels of molecular pharmacology and biochemistry, ex vivo and in vivo electrophysiology, radiography and behavior. Coordinating research efforts across these disciplines and examining cell type- and circuit-specific phenomena are crucial components for translating preclinical findings to viable medical interventions that effectively treat addiction and related disorders.

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Modulation of the endocannabinoid system: Therapeutic potential against cocaine dependence

Cited by 19 publications

References 156 publications

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter

Neurotoxic profiles of HIV, psychostimulant drugs of abuse, and their concerted effect on the brain: Current status of dopamine system vulnerability in NeuroAIDS

Biological substrates of addiction

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