NMDAR dependent intracellular responses associated with cocaine conditioned place preference behavior.
The aim of this study was to investigate the intracellular responses associated with the acquisition and expression of cocaine-context associations. ERK (extracellular regulated kinase), CREB (cAMP responsive element binding protein), FosB and ΔFosB proteins were of particular interest due to their involvement in cocaine reward and in synaptic plasticity underlying learning and memory. We used the conditioned place preference (CPP) paradigm, which employs a Pavlovian conditioning procedure to establish an association between a drug-paired environment and the drug's rewarding effects, to study the role of these signaling pathways in cocaine-context associations. N-methyl-D-aspartate receptor (NMDAR) antagonism prior to cocaine administration during conditioning blocked the acquisition of cocaine CPP and reduced Nucleus Accumbens (NAc) phosphorylated-ERK (pERK) and phosphorylated CREB (pCREB) levels following the CPP test (drug-free). We also show that cocaine-induced increases in Caudate Putamen (CPu) FosB and ΔFosB levels are decreased after MK-801 pre-treatment during conditioning. In addition, our results provide evidence for the involvement of striatal SIRT (Silent Information Regulator of Transcription) proteins in cocaine-CPP. These results will aid in the advancement of general knowledge about the molecular formation and retrieval of cocaine-associated memories that can be used in the future when designing treatments for cocaine addiction that target both prevention and relapse.
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065 USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016 USA. Electronic address: stephanienygard@gmail.com.
Stephanie K
SK
Nygard
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065 USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016 USA. Electronic address: anthonyklambatsen@yahoo.com.
Anthony
A
Klambatsen
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065 USA. Electronic address: bbalouch@gmail.com.
Bailey
B
Balouch
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065 USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016 USA. Electronic address: vaquinon@hunter.cuny.edu.
Vanya
V
Quinones-Jenab
Department of Psychology, Hunter College, CUNY, 695 Park Avenue, New York, NY 10065 USA; Biopsychology and Behavioral Neuroscience Subprogram, Graduate School and University Center, CUNY, 365 Fifth Avenue, New York, NY 10016 USA. Electronic address: sjenab@hunter.cuny.edu.
Shirzad
S
Jenab
D000818:Animals; D050882:CREB-Binding Protein; D003042:Cocaine / Q000494:pharmacology*; D003214:Conditioning, Classical / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism; D056565:Sirtuin 2 / Q000378:metabolism; D013997:Time Factors
D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D016194:Receptors, N-Methyl-D-Aspartate; C097475:Sirt2 protein, rat; D016291:Dizocilpine Maleate; D050882:CREB-Binding Protein; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D056565:Sirtuin 2; D003042:Cocaine
Caudate putamen; Cocaine; Conditioned place preference; NMDARs; Nucleus accumbens
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