Involvement of the dopaminergic system in the reward-related behavior of pregabalin

Sci Rep. 2021 May 19;11(1):10577. doi: 10.1038/s41598-021-88429-8.


There has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / analogs & derivatives
  • Animals
  • Anti-Anxiety Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Dopaminergic Neurons / drug effects
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Pregabalin / pharmacology*
  • Random Allocation
  • Receptors, Dopamine D1 / antagonists & inhibitors*
  • Reward*


  • Anti-Anxiety Agents
  • Drd1 protein, mouse
  • Receptors, Dopamine D1
  • Pregabalin
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
  • 1H-3-benzazepin-7-ol, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-