Dopamine in the dorsal hippocampus impairs the late consolidation of cocaine-associated memory

Neuropsychopharmacology. 2014 Jun;39(7):1645-53. doi: 10.1038/npp.2014.11. Epub 2014 Jan 20.

Abstract

Cocaine is thought to be addictive because it elevates dopamine levels in the striatum, reinforcing drug-seeking habits. Cocaine also elevates dopamine levels in the hippocampus, a structure involved in contextual conditioning as well as in reward function. Hippocampal dopamine promotes the late phase of consolidation of an aversive step-down avoidance memory. Here, we examined the role of hippocampal dopamine function in the persistence of the conditioned increase in preference for a cocaine-associated compartment. Blocking dorsal hippocampal D1-type receptors (D1Rs) but not D2-type receptors (D2Rs) 12 h after a single training trial extended persistence of the normally short-lived memory; conversely, a general and a specific phospholipase C-coupled D1R agonist (but not a D2R or adenylyl cyclase-coupled D1R agonist) decreased the persistence of the normally long-lived memory established by three-trial training. These effects of D1 agents were opposite to those previously established in a step-down avoidance task, and were here also found to be opposite to those in a lithium chloride-conditioned avoidance task. After returning to normal following cocaine injection, dopamine levels in the dorsal hippocampus were found elevated again at the time when dopamine antagonists and agonists were effective: between 13 and 17 h after cocaine injection. These findings confirm that, long after the making of a cocaine-place association, hippocampal activity modulates memory consolidation for that association via a dopamine-dependent mechanism. They suggest a dynamic role for dorsal hippocampal dopamine in this late-phase memory consolidation and, unexpectedly, differential roles for late consolidation of memories for places that induce approach or withdrawal because of a drug association.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine / toxicity*
  • Dopamine Agents / pharmacology
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Hippocampus / drug effects*
  • Lithium Chloride / administration & dosage
  • MAP Kinase Signaling System / drug effects
  • Male
  • Memory Disorders / chemically induced*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / metabolism
  • Time Factors

Substances

  • Brain-Derived Neurotrophic Factor
  • Dopamine Agents
  • Dopamine Uptake Inhibitors
  • Receptor, trkB
  • Lithium Chloride
  • Cocaine
  • Dopamine