Dopamine in the dorsal hippocampus impairs the late consolidation of cocaine-associated memory.
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.
Instituto de Biología Celular y Neurociencias (CONICET-UBA), Facultad de Medicina, UBA, Buenos Aires, Argentina.
Cecilia P
CP
Kramar
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Vladimir I
VI
Chefer
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Roy A
RA
Wise
1] Instituto de Biología Celular y Neurociencias (CONICET-UBA), Facultad de Medicina, UBA, Buenos Aires, Argentina [2] Departamento de Fisiología, Facultad de Medicina, UBA, Buenos Aires, Argentina.
Jorge H
JH
Medina
Instituto de Biología Celular y Neurociencias (CONICET-UBA), Facultad de Medicina, UBA, Buenos Aires, Argentina.
M Flavia
MF
Barbano
D000818:Animals; D001245:Association Learning / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism / Q000633:toxicity*; D015259:Dopamine Agents / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006624:Hippocampus / Q000187:drug effects*; D018021:Lithium Chloride / Q000008:administration & dosage; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D018765:Dopamine Uptake Inhibitors; D020813:Receptor, trkB; D018021:Lithium Chloride; D003042:Cocaine; D004298:Dopamine