Neurobiology of addiction versus drug use driven by lack of choice

Ahmed, Serge H.; Lenoir, Michel; Guillem, Karine

doi:10.1016/j.conb.2013.01.028

Cited by 108 publications

(98 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that early in the drug abuse process administration of cocaine is intermittent, leading to a sensitized cocaine response that facilitates continued drug use, while after long-term use there is tolerance to acute drug effects, an effect that has been reported in human subjects (Mendelson et al, 1998;Reed et al, 2009). It is suggested that in humans, drug use may be based on limited availability, which may lead individuals to administer drug in an intermittent pattern (Ahmed et al, 2013). However, it has also been suggested that LgA self-administration is a model of the escalation that is reported with long-term abuse of the compound in humans (Dackis and O'Brien, 2001).…”

Section: Discussionmentioning

confidence: 99%

Temporal Pattern of Cocaine Intake Determines Tolerance vs Sensitization of Cocaine Effects at the Dopamine Transporter

Calipari

Ferris

Zimmer

et al. 2013

Neuropsychopharmacol

160

121

View full text Add to dashboard Cite

The dopamine transporter (DAT) is responsible for terminating dopamine (DA) signaling and is the primary site of cocaine's reinforcing actions. Cocaine self-administration has been shown previously to result in changes in cocaine potency at the DAT. To determine whether the DAT changes associated with self-administration are due to differences in intake levels or temporal patterns of cocaineinduced DAT inhibition, we manipulated cocaine access to produce either continuous or intermittent elevations in cocaine brain levels. Long-access (LgA, 6 h) and short-access (ShA, 2 h) continuous self-administration produced similar temporal profiles of cocaine intake that were sustained throughout the session; however, LgA had greater intake. ShA and intermittent-access (IntA, 6 h) produced the same intake, but different temporal profiles, with 'spiking' brain levels in IntA compared with constant levels in ShA. IntA consisted of 5-min access periods alternating with 25-min timeouts, which resulted in bursts of high responding followed by periods of no responding. DA release and uptake, as well as the potency of cocaine for DAT inhibition, were assessed by voltammetry in the nucleus accumbens slices following control, IntA, ShA, and LgA self-administration. Continuous-access protocols (LgA and ShA) did not change DA parameters, but the 'spiking' protocol (IntA) increased both release and uptake of DA. In addition, high continuous intake (LgA) produced tolerance to cocaine, while 'spiking' (IntA) produced sensitization, relative to ShA and naive controls. Thus, intake and pattern can both influence cocaine potency, and tolerance seems to be produced by high intake, while sensitization is produced by intermittent temporal patterns of intake.

show abstract

Section: Discussionmentioning

confidence: 99%

Temporal Pattern of Cocaine Intake Determines Tolerance vs Sensitization of Cocaine Effects at the Dopamine Transporter

Calipari

Ferris

Zimmer

et al. 2013

Neuropsychopharmacol

160

121

View full text Add to dashboard Cite

show abstract

“…There is growing awareness that such lack of options may limit the validity of this research for understanding drug addiction as a drug use disorder (Ahmed, 2005(Ahmed, , 2010Ahmed et al, 2013;Alexander and Hadaway, 1982;Cantin et al, 2010;Caprioli et al, 2015b;Carroll et al, 1989;Kerstetter et al, 2012;Le Sage, 2009;Lenoir et al, , 2013Liu and Grigson, 2005;Perry et al, 2013;Thomsen et al, 2013;Tunstall and Kearns, 2013;Zernig et al, 2013). Indeed, when there is no valuable alternative to the drug, drug self-administration may merely reflect a normal reaction to the lack of choice as opposed to reflecting a disordered behavior caused by an underlying dysfunction (Ahmed, 2010;Ahmed et al, 2013;Hyman and Malenka, 2001). As it turns out, providing rats with an alternative nondrug reward, generally a sweet food or drink, during drug access has produced dramatic but contrasting results.…”

Section: Introductionmentioning

confidence: 99%

Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats

Vandaele

Cantin

Serre

et al. 2015

Neuropsychopharmacol

Self Cite

View full text Add to dashboard Cite

Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These settingand drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones.

show abstract

“…Dr Negus reviews literature showing that long-acting DA-selective releasers, such as amphetamine, phenmetrazine, and methamphetamine-but not serotonin releasers such as fenfluramine-indeed reduce cocaine use, both in laboratory animals and people. Perhaps even more importantly they also shift behavioral choice away from cocaine and toward alternative reinforcers, normalizing a characteristic pathology of addiction (Ahmed et al, 2013). Having thus established the efficacy of the 'mimic' approach to reduce cocaine use and choice, Dr Negus turns to the obvious next question, that of safety and tolerability.…”

mentioning

confidence: 99%