Lamotrigine attenuates the motivation to self-administer ketamine and prevents cue- and prime-induced reinstatement of ketamine-seeking behavior in rats

Drug Alcohol Depend. 2019 Jan 1;194:257-263. doi: 10.1016/j.drugalcdep.2018.10.028. Epub 2018 Nov 15.


Background: Lamotrigine is an anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. A case report has demonstrated that a ketamine addict experienced a significant reduction in craving and ketamine use after taking lamotrigine. The present study determined whether lamotrigine can reduce the motivation for ketamine and prevent the relapse to ketamine seeking behavior in rats.

Methods: Male Sprague-Dawley rats were trained to respond for intravenous ketamine (0.5 mg/kg/infusion) self-administration or food pellets. The effects of lamotrigine on the motivation for ketamine or food were assessed using breakpoint test under a progressive ratio (PR) paradigm. Furthermore, the effects of lamotrigine on reinstatement of ketamine-seeking and food-seeking behaviors were examined after extinction.

Results: Lamotrigine significantly decreased the breakpoint for ketamine and prevented cue- and ketamine priming-induced reinstatement of ketamine seeking behavior. However, lamotrigine did not affect the breakpoint for food reinforcement, cue-induced reinstatement of food-seeking behavior, or spontaneous locomotor activity.

Conclusions: Our data reveal that lamotrigine is capable of attenuating the reinforcing efficacy of ketamine and reducing ketamine craving and relapse risk, which lays the foundation for conducting clinical trials in patients with ketamine use disorder.

Keywords: Breakpoint; Extinction; Locomotor activity; Progressive ratio; Relapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage*
  • Animals
  • Anticonvulsants / administration & dosage
  • Cues*
  • Drug-Seeking Behavior / drug effects*
  • Drug-Seeking Behavior / physiology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Ketamine / administration & dosage*
  • Lamotrigine / administration & dosage
  • Locomotion / drug effects
  • Locomotion / physiology
  • Male
  • Motivation / drug effects*
  • Motivation / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology*
  • Self Administration


  • Analgesics
  • Anticonvulsants
  • Ketamine
  • Lamotrigine