Dataset Information

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization.

ABSTRACT: Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate levels in the rat dorsal striatum related to behavioral alterations after repeated administration of cigarette smoke condensate (CSC) using the real-time glutamate biosensing and an open-field behavioral assessment. Repeated administration of CSC including 0.4 mg nicotine (1.0 mL/kg/day, subcutaneous) for 14 days significantly increased extracellular glutamate concentrations more than repeated nicotine administration. In parallel with the hyperactivation of glutamate levels, repeated administration of CSC-evoked prolonged hypersensitization of psychomotor activity, including locomotor and rearing activities. These findings suggest that the CSC-induced psychomotor activities are closely associated with the elevation of glutamate concentrations in the rat dorsal striatum.

SUBMITTER: Ryu IS

PROVIDER: S-EPMC5864865 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization.

Ryu In Soo IS Kim Jieun J Seo Su Yeon SY Yang Ju Hwan JH Oh Jeong Hwan JH Lee Dong Kun DK Cho Hyun-Wook HW Lee Kyuhong K Yoon Seong Shoon SS Seo Joung-Wook JW Shim Insop I Choe Eun Sang ES

Frontiers in behavioral neuroscience 20180316

Nicotine, a nicotinic acetylcholine receptor agonist, produces the reinforcing effects of tobacco dependence by potentiating dopaminergic and glutamatergic neurotransmission. Non-nicotine alkaloids in tobacco also contribute to dependence by activating the cholinergic system. However, glutamatergic neurotransmission in the dorsal striatum associated with behavioral changes in response to cigarette smoking has not been investigated. In this study, the authors investigated alterations in glutamate ...[more]

PMID: 29615877

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Project description:BackgroundThe N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Using Srr knock-out (KO) mice, we investigated the role of SRR on METH-induced behavioral abnormalities in mice.Methodology/principal findingsEvaluations of behavior in acute hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP) were performed. The role of SRR on the release of dopamine (DA) in the nucleus accumbens after administration of METH was examined using in vivo microdialysis technique. Additionally, phosphorylation levels of ERK1/2 proteins in the striatum, frontal cortex and hippocampus were examined using Western blot analysis. Acute hyperlocomotion after a single administration of METH (3 mg/kg) was comparable between wild-type (WT) and Srr-KO mice. However, repeated administration of METH (3 mg/kg/day, once daily for 5 days) resulted in behavioral sensitization in WT, but not Srr-KO mice. Pretreatment with D-serine (900 mg/kg, 30 min prior to each METH treatment) did not affect the development of behavioral sensitization after repeated METH administration. In the CPP paradigm, METH-induced rewarding effects were demonstrable in both WT and Srr-KO mice. In vivo microdialysis study showed that METH (1 mg/kg)-induced DA release in the nucleus accumbens of Srr-KO mice previously treated with METH was significantly lower than that of the WT mice previously treated with METH. Interestingly, a single administration of METH (3 mg/kg) significantly increased the phosphorylation status of ERK1/2 in the striatum of WT, but not Srr-KO mice.Conclusions/significanceThese findings suggest first, that SRR plays a role in the development of behavioral sensitization in mice after repeated administration of METH, and second that phosphorylation of ERK1/2 by METH may contribute to the development of this sensitization as seen in WT but not Srr-KO mice.

Dataset Information

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization.

Publications

Repeated Administration of Cigarette Smoke Condensate Increases Glutamate Levels and Behavioral Sensitization.

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