Nicotine-conditioned place preference induced CREB phosphorylation and Fos expression in the adult rat brain.
BACKGROUND
Experimental evidence indicates that nicotine causes long-lasting changes in the brain associated with behavior. Although much has been learned about factors participating in this process, less is known concerning the mechanisms and brain areas involved in nicotine preference.


OBJECTIVE
The objective of this study is to examine the participation of brain structures during the development of nicotine-conditioned place preference (CPP).


METHODS
To identify brain regions activated in CPP, we have measured the levels of phosphorylated cyclic AMP response element binding protein (pCREB) and Fos protein using a behavioral CPP and conditioned place aversion (CPA) paradigms.


RESULTS
Rats developed reliable and robust CPP and also CPA. During nicotine preference and reinstatement behaviors, a significant increase of both pCREB and Fos protein expression occurs in the nucleus accumbens (NAc) and ventral tegmental area (VTA) and also in the prefrontal cortex (PFC), dorsal striatum (DStr), amygdala, and hippocampus. These increases were abolished by the administration of mecamylamine or by a CPA protocol, showing a specific activation of pCREB in drug preference animals, mediated by nicotinic receptors. Specifically in the VTA, nicotine-induced preference and reinstatement of the preference caused the activation of dopaminergic and GABAergic cells in different proportions.


CONCLUSIONS
The results indicate that the phosphorylation of CREB and expression of Fos protein, as indicators of neural activity, accompany the acquisition and maintenance of nicotine-induced CPP but not CPA in mesolimbic areas (NAc, VTA, PFC, and DStr) as well as in memory consolidation structures (hippocampus and amygdala) and nicotinic receptor are involved in this process. Taken together, these studies identify the brain regions where pCREB activity is essential for nicotine preference.
Pascual
Mariano M
MM
Department of Physiology and Institute of Cell Biology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina.
Pastor
Veronica
V
Bernabeu
Ramon O
RO
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism*; D002452:Cell Count / Q000379:methods; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D016761:Oncogene Proteins v-fos; D008464:Mecamylamine; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D050882:CREB-Binding Protein; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1