Lamotrigine reduces motivation and relapse for ketamine self-administration in rats

[Speaker] Yu-Ching Hsiao:1
[Co-author] Hwei-Hsien Chen:1,2, Mei-Yi Lee:1,2
1:R1-5121, 35 Keyan Road, Zhunan, Miaoli County 35053, Taiwan, 2:Department of Pharmacology and Toxicology Tzu Chi University, Hualien, Taiwan

Ketamine has become a popular recreational drug of abuse among young people, resulting in an important medical issue due to its addiction liability. One case report has demonstrated that a ketamine addict experienced a great reduction in craving and ketamine use after taking lamotrigine, an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. The present study determined whether lamotrigine can reduce the reinforcing and motivational effects of ketamine and prevent the relapse to drug seeking behavior in rats.
Male Sprague-Dawley rats were submitted to ketamine intravenous self-administration training under fixed ratio schedules. The effects of lamotrigine on the motivation to work for ketamine (0.3 and 0.5 mg/kg) were assessed in the breakpoint test under a progressive ratio (PR) paradigm. The relapse-like behavior in the cue- and ketamine-induced reinstatement test was examined after extinction. In addition, the effect of Lamotrigine on the locomotor activity was monitored. Lamotrigine (10 and 30 mg/kg) was administered 30 min prior to each test.
Lamotrigine (30 mg/kg) significantly decreased the PR breakpoints and cue- and ketamine-induced reinstatement, but not affect locomotor activity, demonstrating that lamotrigine can reduce the reinforcing effect of ketamine and ketamine-seeking behavior.
Our data support the hypothesis that lamotrigine is capable of reducing the reinforcing efficacy of ketamine and also lowering the risk of relapse.

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