Full Text:   <2140>

CLC number: Q42; R99

On-line Access: 

Received: 2005-07-19

Revision Accepted: 2005-11-18

Crosschecked: 0000-00-00

Cited: 25

Clicked: 5117

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
1. Reference List
Open peer comments

Journal of Zhejiang University SCIENCE B 2006 Vol.7 No.2 P.107-113


Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats

Author(s):  Zhou Lian-fang, Zhu Yong-ping

Affiliation(s):  Department of Toxicology, School of Medicine, Zhejiang University, Hangzhou 310006, China; more

Corresponding email(s):   zhoulianfang@163.com, zhuyp@zju.edu.cn

Key Words:  Conditioned place preference (CPP), Morphine, Video tracking, CREB (cAMP response element binding protein)

Zhou Lian-fang, Zhu Yong-ping. Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats[J]. Journal of Zhejiang University Science B, 2006, 7(2): 107-113.

@article{title="Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats",
author="Zhou Lian-fang, Zhu Yong-ping",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats
%A Zhou Lian-fang
%A Zhu Yong-ping
%J Journal of Zhejiang University SCIENCE B
%V 7
%N 2
%P 107-113
%@ 1673-1581
%D 2006
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.2006.B0107

T1 - Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats
A1 - Zhou Lian-fang
A1 - Zhu Yong-ping
J0 - Journal of Zhejiang University Science B
VL - 7
IS - 2
SP - 107
EP - 113
%@ 1673-1581
Y1 - 2006
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.2006.B0107

Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC (prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas. Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve activation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Barrot, M., Olivier, J.D., Perrotti, L.I., DiLeone, R.J., Berton, O., Eisch, A.J., Impey, S., Storm, D.R., Neve, R.L., Yin, J.C., et al., 2002. CREB activity in the nucleus accumbens shell controls gating of behavioral responses to emotional stimuli. Neurobiology, 99:11435-11440.

[2] Berke, J.D., Eichenbaum, H.B., 2001. Drug addiction and the hippocampus. Science, 294(5545):1235a.

[3] Black, Y., Green-Jordan, K., Eichenbaum, H.B., Kantak, K.M., 2004. Hippocampal memory system function and the regulation of cocaine self-administration behavior in rats. Brain Research, 151:225-238.

[4] Capriles, N., Rodaros, D., Sorge, R.E., Stewart, J., 2003. A role for the prefrontal cortex in stress and cocaine-induced reinstatement of cocaine seeking in rats. Psychopharmacology, 168(1-2):66-74.

[5] Di Chiara, G., 2002. Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behavioural Brain Research, 137(1-2):75-114.

[6] García-Sevilla, J.A., Ferrer-Alcón, M., Martín, M., Kieffer, B.L., Maldonado, R., 2004. Neurofilament proteins and cAMP pathway in brains of μ-, δ- or κ-opioid receptor gene knock-out mice: effects of chronic morphine administration. Neuropharmacology, 46(4):519-530.

[7] Goldstein, R.Z., Volkow, N.D., 2002. Drug addiction and its underlying neurobiological basis: neuroimaging evidence for the involvement of the frontal cortex. Am. J. Psychiatry, 159(10):1642-1652.

[8] Li, J., Li, Y.H., Yuan, X.R., 2003. Changes of phosphorylation of cAMP response element binding protein in rat nucleus accumbens after chronic ethanol intake: naloxone reversal. Acta Pharmacol. Sin., 24(9):930-936.

[9] Mueller, D., Stewart, J., 2000. Cocaine-induced conditioned place preference: reinstatement by priming injections of cocaine after extinction. Behavioural Brain Research, 115(1):39-47.

[10] Mueller, D., Perdikaris, D., Stewart, J., 2002. Persistence and drug-induced reinstatement of a morphine-induced conditioned place preference. Behavioural Brain Research, 136(2):389-397.

[11] Nestler, E.J., 2002. Common molecular and cellular substrates of addiction and memory. Neurobiology of Learning and Memory, 78(3):637-647.

[12] Nestler, E.J., Barrot, M., Self, D.W., 2001. ΔFosB: a sustained molecular switch for addiction. Proc. Natl. Acad. Sci., 98:11042-11046.

[13] Parker, L.A., Mcdonald, R.V., 2000. Reinstatement of both a conditioned place preference and a conditioned place aversion with drug primes. Pharmacology Biochemistry and Behavior, 66(3):559-561.

[14] Paxinis, G., Watson, C., 1998. The Rat Brain in Stereotaxic Coordinates, 4th ED. Academic Press, USA, p.1-130.

[15] Rhodes, J.S., Crabbe, J.C., 2005. Gene expression induced by drugs of abuse. Current Opinion in Pharmacology, 5(1):26-33.

[16] Sanchez, C.J., Bailie, T.M., Wu, W.R., Li, N., Sorg, B.A., 2003. Manipulation of dopamine D1-like receptor activation in the rat medial prefrontal cortex alters stress and cocaine-induced reinstatement of conditioned place preference behavior. Neuroscience, 119(2):497-505.

[17] Self, D.W., Choi, K.H., Simmons, D., Walker, J.R., Smagula, C.S., 2004. Extinction training regulates neuroadaptive responses to withdrawal from chronic cocaine self-administration. Learning & Memory, 11(5):648-657.

[18] Shippenberg, T.S., Heidbreder, C., Lefevour, A., 1996. Sensitization to the conditioned rewarding effects of morphine: pharmacology and temporal characteristics. European Journal of Pharmacology, 299(1-3):33-39.

[19] Thompson, A.M., Gosnell, B.A., Wagner, J.J., 2002. Enhancement of long-term potentiation in the rat hippocampus following cocaine exposure. Neuropharmacology, 42(8):1039-1042.

[20] Vetulani, J., 2001. Drug addiction. Part II. Neurobiology of addiction. J. VETULANI. Pol. J. Pharmacol, 53:303-317.

[21] Vorel, S.R., Liu, X., Hayes, R.J., Spector, J.A., Gardner, E.L., 2001. Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science, 292(5519):1175-1178.

[22] Widnell, K.L., Self, D.W., Lane, S.B., Russell, D.S., Vaidya, V.A., Miserendino, M.J., Rubin, C.S., Duman, R.S., Nestler, E.J., 1996. Regulation of CREB expression: in vivo evidence for a functional role in morphine action in the nucleus accumbens. J. Pharmacol. Exp. Ther., 276(1):306-315.

[23] Zavala, A.R., Weber, S.M., Rice, H.J., Alleweireldt, A.T., Neisewander, J.L., 2003. Role of the prelimbic subregion of the medial prefrontal cortex in acquisition, extinction, and reinstatement of cocaine-conditioned place preference. Brain Research, 990(1-2):157-164.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE