Expression pattern of neural synaptic plasticity marker-Arc in different brain regions induced by conditioned drug withdrawal from acute morphine-dependent rats.
OBJECTIVE
The immediate early gene Arc (activity-regulated cytoskeletal-associated protein) mRNA and protein are induced by strong synaptic activation and rapidly transported into dendrites, where they localize at active synaptic sites. Thus, the Arc mRNA and protein are proposed as a marker of neuronal reactivity to map the neural substrates that are recruited by various stimuli. In the present study, we examined the expression of Arc protein induced by conditioned naloxone-precipitated drug withdrawal in different brain regions of acute morphine-dependent rats. The objective of the present study was to address the specific neural circuits involved in conditioned place aversion (CPA) that has not yet been well characterized.


METHODS
Place aversion was elicited by conditioned naloxone-precipitated drug withdrawal following exposure to a single dose of morphine. An immunohistochemical method was employed to detect the expression of Arc, which was used as a plasticity marker to trace the brain areas that contribute to the formation of the place aversion.


RESULTS
Marked increases in Arc protein levels were found in the medial and lateral prefrontal cortex, the sensory cortex, the lateral striatum and the amygdala. This effect was more pronounced in the basolateral amygdala (BLA), the central nucleus of the amygdala (CeA), and the bed nucleus of the striatal terminals (BNST) when compared with the control group.


CONCLUSIONS
Our results suggest that these brain regions may play key roles in mediating the negative motivational component of opiate withdrawal.
Li
Mu
M
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Hou
Yuan-yuan
YY
Lu
Bin
B
Chen
Jie
J
Chi
Zhi-qiang
ZQ
Liu
Jing-gen
JG
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D003213:Conditioning, Psychological / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009021:Morphine Dependence / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D003598:Cytoskeletal Proteins; D009292:Narcotic Antagonists; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D009270:Naloxone; D009020:Morphine