Dopamine D1 and D3 receptors mediate reconsolidation of cocaine memories in mouse models of drug self-administration

Neuroscience. 2014 Oct 10;278:154-64. doi: 10.1016/j.neuroscience.2014.08.008. Epub 2014 Aug 20.


Memories of drug experience and drug-associated environmental cues can elicit drug-seeking and taking behaviors in humans. Disruption of reconsolidation of drug memories dampens previous memories and therefore may provide a useful way to treat drug abuse. We and others previously demonstrated that dopamine D1 and D3 receptors play differential roles in acquiring cocaine-induced behaviors. Moreover, D3 receptors contribute to the reconsolidation of cocaine-induced conditioned place preference. In the present study, we examined effects of manipulating D1 or D3 receptors on reconsolidation of cocaine memories in mouse models of drug self-administration. We found that pharmacological blockade of D1 receptors or a genetic mutation of the D3 receptor gene attenuated reconsolidation that lasted for at least 1week after the memory retrieval. In contrast, with no memory retrieval, pharmacological antagonism of D1 receptors or the D3 receptor gene mutation did not significantly affect reconsolidation of cocaine memories. Pharmacological blockade of D3 receptors also attenuated reconsolidation in wild-type mice that lasted for at least 1week after the memory retrieval. These results suggest that D1 and D3 receptors and related signaling mechanisms play key roles in reconsolidation of cocaine memories in mice, and that these receptors may serve as novel targets for the treatment of cocaine abuse in humans.

Keywords: antagonists; cocaine self-administration; dopamine D1 and D3 receptors; drug memory; gene mutation; reconsolidation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzamides
  • Benzazepines / pharmacology
  • Cocaine / pharmacology*
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology*
  • Female
  • Male
  • Memory / drug effects
  • Memory / physiology*
  • Mental Recall / drug effects
  • Mental Recall / physiology
  • Mice
  • Mice, Knockout
  • Pyridines
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / physiology*
  • Receptors, Dopamine D3 / antagonists & inhibitors
  • Receptors, Dopamine D3 / genetics
  • Receptors, Dopamine D3 / physiology*
  • Self Administration


  • Benzamides
  • Benzazepines
  • N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)but-2-enyl)-4-pyridine-2-ylbenzamide
  • Pyridines
  • Receptors, Dopamine D1
  • Receptors, Dopamine D3
  • SCH 23390
  • Cocaine