Acamprosate attenuates cocaine- and cue-induced reinstatement of cocaine-seeking behavior in rats

Abstract

Acamprosate attenuates both drug- and cue-induced reinstatement of cocaine-seeking behavior, suggesting that this compound may serve as a potential treatment for preventing relapse in cocaine-addicted humans.

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

“…In preclinical studies, systemic administration of acamprosate inhibits cue-induced and drug-primed cocaine seeking (Bowers et al, 2007), cueinduced nicotine seeking (Pechnick et al, 2011), as well as cocaine and ethanol CPP (McGeehan and Olive, 2003a) and the reinstatement of cocaine CPP (McGeehan and Olive, 2006). Interestingly, acamprosate inhibits morphine-induced sensitization (but does not inhibit stress or drug-primed reinstatement of heroin seeking), an effect that is accompanied by reduced dopamine levels in the NAshell (Spanagel et al, 1998).…”

Acamprosate modulates experimental autoimmune encephalomyelitis

“…But the administration of 500 mg/kg acamprosate in the absence of EAE had no effect on BW gain, suggesting that immune activation in the EAE mice may interact with acamprosate to suppress BW gain. Bowers et al (2007) did not observe an effect of 100 and 300 mg/kg on BW gain in rats, but 500 mg/kg acamprosate did reduce BW gain.…”

“…These results suggest that a shorter duration of high doses of acamprosate or a longer duration of low doses of acamprosate is required for optimum beneficial effects, and that long-term administration of high doses of acamprosate may adversely affect EAE disease severity. This assumption is supported by a study (Bowers et al 2007) showing that repeated administration of 500 mg/kg acamprosate, and not lower doses, had adverse effects reducing the locomotor activity in rats. Therefore, both the dose and the length of acamprosate's administration can affect the EAE disease severity.…”

“…The selected doses of 20, 100 and 500 mg/kg were based on earlier studies of rodent models of alcohol dependence and morphine and nicotine seeking behaviors (Czachowski and Delory 2009;Bowers et al 2007;McGeehan and Olive 2003) and were, respectively, equivalent to 0.7 time, 3.5 times and 17.7 times the therapeutic dose of 2 g/day (equivalent to 28.5 mg/kg) acamprosate in an average 70 kg human subject. Earlier studies (Czachowski and Delory 2009;Bowers et al 2007;McGeehan and Olive 2003) used acamprosate in wide ranges of 30-500 mg/kg. However, consistent with our results, the observed acamprosate's efficacy in reducing alcohol craving and morphine and nicotine seeking behavior was mostly observed in doses of C100 mg/kg.…”

Cocaine Addiction: Changes in Excitatory and Inhibitory Neurotransmission

“…Tiagabine is yet another anticonvulsant that increases GABA neurotransmission by blocking the presynaptic reuptake of GABA. In 2 randomized clinical trials involving cocaine dependent patients who were maintained on methadone, tiagabine (12-24 mg/day) was found to decrease cocaine use compared with placebo (Bowers et al, 2007;Gonzalez et al, 2003) .…”