Narp deletion blocks extinction of morphine place preference conditioning.
As drug abuse can be viewed as a maladaptive form of neuronal plasticity, attention has focused on defining the synaptic plasticity mechanisms that mediate the long-term effects of these drugs. As Narp is secreted at synaptic sites and binds to the extracellular surface of AMPA receptors, it has been implicated in mediating enduring forms of synaptic plasticity. Accordingly, to assess its potential role in the long-lasting behavioral effects of drugs of abuse, we have investigated the impact of Narp deletion on sustained behavioral responses elicited by repeated morphine administration. Narp knockout mice display normal locomotor sensitization and conditioned place preference, but are markedly resistant to extinction of place preference. Thus, these findings indicate that Narp plays a selective role in extinction, possibly by its effects on AMPA receptor trafficking.
Crombag
Hans S
HS
Department of Psychological and Brain Sciences, Neurogenetics and Behavior Center, The Johns Hopkins University, Baltimore, MD, USA. h.crombag@sussex.ac.uk
Dickson
Mercy
M
Dinenna
Megan
M
Johnson
Alexander W
AW
Perin
Mark S
MS
Holland
Peter C
PC
Baraban
Jay M
JM
Reti
Irving M
IM
D000818:Animals; D016739:Behavior, Addictive / Q000503:physiopathology; D002097:C-Reactive Protein / Q000235:genetics / Q000502:physiology*; D003213:Conditioning, Psychological; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D018091:Receptors, AMPA / Q000378:metabolism; D000099153:Pentraxins
D002097:C-Reactive Protein; D009020:Morphine; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D000099153:Pentraxins