Cocaine addiction: treatments and future perspectives

Sánchez-Hervás, Emilio

doi:10.1590/2237-6089-2016-0013

Cited by 2 publications

(1 citation statement)

References 7 publications

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“…Several pharmacological approaches are presently under study for treating cocaine addiction, but none is approved by North American, European or other agencies (1)(2)(3). One promising strategy is to substitute cocaine with another dopaminergic agent (4), such as D-amphetamine, but in a slower and longer-acting formulation that would be potentially less harmful.…”

Section: Introductionmentioning

confidence: 99%

Amphetamine Maintenance Therapy During Intermittent Cocaine Self-Administration in Rats: Reduction of Addiction-like Behavior is Associated with Attenuation of Psychomotor and Dopamine Sensitization

Allain

Delignat-Lavaud

Beaudoin

et al. 2020

Preprint

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Background. D-amphetamine maintenance therapy shows promise as a treatment for people with cocaine addiction. Preclinical studies using Long Access (LgA) cocaine self-administration procedures suggest Damphetamine may act by preventing tolerance to cocaine's effects at the dopamine transporter (DAT). However, Intermittent Access (IntA) cocaine self-administration better reflects human patterns of use, is especially effective in promoting addiction-relevant behaviors, and instead of tolerance, produces psychomotor, incentive, and neural sensitization. We asked, therefore, how D-amphetamine maintenance during IntA influences cocaine use and cocaine's potency at the DAT.Methods. Male rats self-administered cocaine intermittently (5 minutes ON, 25 minutes OFF x 10) for 14 sessions, with or without concomitant D-amphetamine (5 mg/kg/day via s.c. osmotic minipump). In Experiment 1, psychomotor sensitization, responding for cocaine under a progressive ratio schedule, responding under extinction and cocaine-primed relapse were assessed. In Experiment 2, rats self-administered cocaine or saline intermittently, with or without D-amphetamine, and the ability of cocaine to inhibit dopamine uptake in the nucleus accumbens core was assessed using fast scan cyclic voltammetry ex vivo.Results. IntA cocaine self-administration produced psychomotor sensitization, strong motivation to take and seek cocaine, and it increased cocaine's potency at the DAT. The co-administration of D-amphetamine suppressed both the psychomotor sensitization and high motivation for cocaine produced by IntA experience, and also reversed sensitization of cocaine's actions at the DAT, leaving baseline DAT function unchanged. Conclusions.Treatment with D-amphetamine might reduce cocaine use by preventing sensitization-related changes in cocaine potency at the DAT, consistent with an incentive-sensitization view of addiction.

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