Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats

Narita, Minoru; Akai, Hiroyuki; Nagumo, Yoko; Sunagawa, Norio; Hasebe, Ko; Nagase, Hiroshi; Kita, Taizo; Hara, Chiaki; Suzuki, Tsutomu

doi:10.1016/j.neuroscience.2004.06.017

Cited by 57 publications

(35 citation statements)

References 28 publications

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“…Of these genes, BDNF has been identified in multiple microarray studies using cocaine with various transgenic mouse models as well as affecting cocaine induced behaviors in BDNF heterozygotic knockout mice (Hall et al, 2003;McClung and Nestler, 2003;Yao et al, 2004). Furthermore, changes in Prkca activity have been shown to alter psychostimulant mediated behavior or to be altered by psychostimulant exposure (Aujla and Beninger, 2003;Narita et al, 2004;Steketee et al, 1998). Therefore, the affects of BDNF and Prkca on psychostimulant-mediated behavior might be of particular interest for further study.…”

Section: Discussionmentioning

confidence: 99%

Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization

et al. 2008

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We have expressed A-FOS, an inhibitor of AP-1 DNA binding, in adult mouse striatal neurons. We observe normal behavior including locomotion and exploratory activities. Following a single injection of cocaine, locomotion increased similarly in both the A-FOS expressing and littermate controls. However, following repeated injections of cocaine, the A-FOS expressing mice showed increased locomotion relative to littermate controls, an increase that persisted following a week of withdrawal and subsequent cocaine administration. These results indicate that AP-1 suppresses this behavioral responses to cocaine. We analyzed mRNA from the striatum before and 4 and 24 hours after a single cocaine injection in both A-FOS and control striata using Affymetrix microarrays (430 2.0 Array) to identify genes mis-regulated by A-FOS that may mediate the increased locomotor sensitization to cocaine. A-FOS expression did not change gene expression in the basal state or 4 hours following cocaine treatment relative to controls. However, 24 hours after an acute cocaine treatment, 84 genes were identified that were differentially expressed between the A-FOS and control mice. 56 gene are down regulated while 28 genes are up regulated including previously identified candidates for addiction including BDNF and Per1. Using a random sample of identified genes, quantitative PCR was used to verify the microarray studies. The chromosomal location of these 84 genes was compared to human genome scans of addiction to identify potential genes in humans that are involved in addiction. Keywords A-FOS; addiction; sensitization; gene expressionPsychostimulants can produce a persistent state of compulsive drug use known as addiction. Although, there is much evidence that both the rewarding and addictive properties of these *To whom correspondence should be addressed. Laboratory of Metabolism, National Cancer Institute, NIH; Bldg. 37, Rm. 3128 Bethesda, Md. 20892. Tel:301-496-8753, Fax:301-496-8419 E-mail: Vinsonc@dc37a.nci.nih.gov. 4 Present address Laboratory of Systems Neuroscience, National Institute of Mental Health, NIH: Bldg 35 Rm 3A1014 Bethesda, MD 20892. 5 Present address Office of Provost, Massachusetts Hall, Harvard University, Cambridge, MA.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 November 20. Published in final edited form as:Neuroscience. (Di Chiara and Imperato, 1988;Hurd and Ungerstedt, 1989;Kalivas and Duffy, 1990;Robbins and Everitt, 1996), the downstream effects are not well understood at...

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Section: Discussionmentioning

confidence: 99%

Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization

et al. 2008

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“…These behaviors can be modeled by using the consumption of reward and conditioned place preference (CPP) paradigms [56]. Interestingly, selective (NPC-15437, chelerythrine, calphostin C) and non-selective (H-7) PKC inhibitors, regardless of the brain region in which they are injected (amygdala, nucleus accumbens, or more widely in the lateral ventricle), diminished the CPP induced by several drugs of abuse (morphine, cocaine, or methamphetamine) [57][58][59][60]. Targeted genetic deletions also support the involvement of PKC in such affective-like behaviors.…”

Section: Behavioral Effects Of Pkc Modulators On Animal Models Of Manmentioning

confidence: 99%

A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

et al. 2011

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Mood disorders, such as bipolar and major depressive disorders, are frequent, severe, and often disabling neuropsychiatric diseases affecting millions of individuals worldwide. Available mood stabilizers and antidepressants remain unsatisfactory because of their delayed and partial therapeutic efficacy. Therefore, the development of targeted therapies, working more rapidly and being fully effective, is urgently needed. In this context, the protein kinase C (PKC) signaling system, which regulates multiple neuronal processes implicated in mood regulation, can constitute a novel therapeutic target. This paper reviews the currently available knowledge regarding the role of the PKC signaling pathway in the pathophysiology of mood disorders and the therapeutic potential of PKC modulators. Current antidepressants and mood stabilizers have been shown to modulate the PKC pathway, and the inhibition of this intracellular signaling cascade results in antimanic-like properties in animal models. Disrupted PKC activity has been found both in postmortem brains and platelet from patients with mood disorders. Finally, the PKC inhibitor tamoxifen has recently demonstrated potent antimanic properties in several clinical trials. Overall, emerging data from preclinical and clinical research suggest an imbalance of the PKC signaling system in mood disorders. Thus, PKC may be a critical molecular target for the development of innovative therapeutics.

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“…Most investigators have reported that an enhanced DA response in the nucleus accumbens (40), striatum (41,42), and prefrontal cortex (43) may underlie behavioral sensitization, while some investigators have shown that behavioral sensitization can be obtained in the absence of an enhanced DA response in the DA projection regions (8 -12). The apparent discrepancy may be due to differences in the conditions for induction of behavioral sensitization such as stimulant treatment and period of drug withdrawal (44).…”

Section: Neurochemical Effects Of Repeated Methamphetamine Administramentioning

confidence: 99%

Neuropsychotoxicity of Abused Drugs: Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice

et al. 2008

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Abstract. Repeated administration of psychostimulants elicits a progressive enhancement of locomotor activity known as behavioral sensitization. Central dopamine (DA) neurons play key roles as the neural substrates mediating behavioral sensitization, but the role of the serotonin (5-HT) system in the sensitization is not fully elucidated. We have recently demonstrated that osemozotan, a specific 5-HT 1A -receptor agonist, and ritanserin, a 5-HT 2 -receptor antagonist, inhibited the expression and development of both methamphetamine-and cocaine-induced behavioral sensitization in mice and that these drugs attenuated the maintenance of behavioral sensitization of methamphetamine, but not that of cocaine. We also found that azasetron, a 5-HT 3 -receptor antagonist, inhibited the expression and development of the sensitization induced by methamphetamine and cocaine, respectively. Neurochemical studies using a microdialysis technique showed that repeated methamphetamine enhanced the methamphetamine-induced increase in 5-HT release in the prefrontal cortex. The sensitization of 5-HT release in methamphetamine-treated mice was attenuated by osemozotan and ritanserin. These findings suggest that the 5-HT system plays an important role in methamphetamine-and cocaine-induced behavioral sensitization in mice and imply that 5-HT 1A -receptor agonists and 5-HT 2 -receptor antagonists may have a potential therapeutic value for the treatment of methamphetamine abuse or psychosis.

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Implications of protein kinase C in the nucleus accumbens in the development of sensitization to methamphetamine in rats

Cited by 57 publications

References 28 publications

Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization

Inhibiting activator protein-1 activity alters cocaine-induced gene expression and potentiates sensitization

A Role for the PKC Signaling System in the Pathophysiology and Treatment of Mood Disorders: Involvement of a Functional Imbalance?

Neuropsychotoxicity of Abused Drugs: Effects of Serotonin Receptor Ligands on Methamphetamine- and Cocaine-Induced Behavioral Sensitization in Mice

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