Article

Neuroadaptations in the cellular and postsynaptic group 1 metabotropic glutamate receptor mGluR5 and Homer proteins following extinction of cocaine self-administration.

Department of Biomedical Sciences, Integrative Neuroscience Research Center, Marquette University, Milwaukee, WI 53201, United States.
Neuroscience Letters (impact factor: 2.11). 01/2009; 452(2):167-71. DOI:10.1016/j.neulet.2008.12.028
Source: PubMed

ABSTRACT This study examined the role of group1 metabotropic glutamate receptor mGluR5 and associated postsynaptic scaffolding protein Homer1b/c in behavioral plasticity after three withdrawal treatments from cocaine self-administration. Rats self-administered cocaine or saline for 14 days followed by a withdrawal period during which rats underwent extinction training, remained in their home cages, or were placed in the self-administration chambers in the absence of extinction. Subsequently, the tissue level and distribution of proteins in the synaptosomal fraction associated with the postsynaptic density were examined. Cocaine self-administration followed by home cage exposure reduced the mGluR5 protein in nucleus accumbens (NA) shell and dorsolateral striatum. While extinction training reduced mGluR5 protein in NAshell, NAcore and dorsolateral striatum did not display any change. The scaffolding protein PSD95 increased in NAcore of the extinguished animals. Extinction of drug seeking was associated with a significant decrease in the synaptosomal mGluR5 protein in NAshell and an increase in dorsolateral striatum, while that of NAcore was not modified. Interestingly, both Homer1b/c and PSD95 scaffolding proteins were decreased in the synaptosomal fraction after extinction training in NAshell but not NAcore. Extinguished drug-seeking behavior was also associated with an increase in the synaptosomal actin proteins in dorsolateral striatum. Therefore, extinction of cocaine seeking is associated with neuroadaptations in mGluR5 expression and distribution that are region-specific and consist of extinction-induced reversal of cocaine-induced adaptations as well as emergent extinction-induced alterations. Concurrent plasticity in the scaffolding proteins further suggests that mGluR5 receptor neuroadaptations may have implications for synaptic function.

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Keywords

cocaine self-administration
 
cocaine-induced adaptations
 
emergent extinction-induced alterations
 
extinction training
 
extinguished animals
 
Extinguished drug-seeking behavior
 
home cage exposure
 
home cages
 
mGluR5 protein
 
mGluR5 receptor neuroadaptations
 
postsynaptic density
 
postsynaptic scaffolding protein Homer1b/c
 
PSD95 scaffolding proteins
 
Rats self-administered cocaine
 
scaffolding protein PSD95
 
self-administration chambers
 
synaptic function
 
synaptosomal actin proteins
 
synaptosomal mGluR5 protein
 
withdrawal treatments