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NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.
Department of Molecular Neuropharmacology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland.
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences , 31-343 Krakow, Poland..
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
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2016 (English)In: eNeuro, ISSN 2373-2822, Vol. 3, no 3, ENEURO.0084-15.2016Article in journal (Refereed) Published
Abstract [en]

Plasticity of the brain's dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1(D1CreERT2) mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1(D1CreERT2) mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

Place, publisher, year, edition, pages
2016. Vol. 3, no 3, ENEURO.0084-15.2016
Keyword [en]
NMDA receptors, dopamine, drugs of abuse, operant conditioning, reinforcement
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-135355DOI: 10.1523/ENEURO.0084-15.2016PubMedID: 27294197OAI: oai:DiVA.org:liu-135355DiVA: diva2:1081237
Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2017-03-29Bibliographically approved

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Zajdel, JoannaEngblom, David
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