Narp regulates long-term aversive effects of morphine withdrawal.
Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction.
Reti
Irving M
IM
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland, USA. imreti@jhmi.edu
Crombag
Hans S
HS
Takamiya
Kogo
K
Sutton
Jeffrey M
JM
Guo
Ning
N
Dinenna
Megan L
ML
Huganir
Richard L
RL
Holland
Peter C
PC
Baraban
Jay M
JM
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002097:C-Reactive Protein / Q000172:deficiency / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000009:adverse effects*; D009271:Naltrexone / Q000008:administration & dosage; D009292:Narcotic Antagonists / Q000008:administration & dosage; D009294:Narcotics / Q000009:adverse effects*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D012153:Retention, Psychology / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D000099153:Pentraxins
D002097:C-Reactive Protein; D009020:Morphine; D009271:Naltrexone; D009292:Narcotic Antagonists; D009294:Narcotics; D009419:Nerve Tissue Proteins; D000099153:Pentraxins