期刊
BEHAVIOURAL BRAIN RESEARCH
卷 220, 期 1, 页码 126-131出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbr.2011.01.031
关键词
Memantine; Cocaine memory; Conditioning; Cytokine; Nucleus accumbens
资金
- ROC National Science Council [97-2321-B-006-010, 97-2410-H-006-074-MY3]
In this study, we decided to use low doses of memantine pretreatment to examine the roles of the immune function in cocaine-supported conditioning. Cocaine-induced conditioned place preference (CPP) was used to assess the hedonic value and/or reinforcing efficacy of cocaine and cocaine-supported conditioning. Systemic pretreatment with memantine (20, 2.0, 0.2, and 0.02 mg/kg/injection) 30 min before each cocaine and saline conditioning trial abolished the acquisition of cocaine-induced CPP in mice. Even a total of 0.12 mg/kg memantine pretreatment in three days was effective in diminishing cocaine-induced CPP. Three consecutive days of cocaine conditioning increased interleukin-6 (IL-6) but decreased tumor necrosis factor (TNF-alpha) levels in medial prefrontal cortex (mPFC) and nucleus accumbens (Acb). Interestingly, pretreatment with memantine at the lowest effective dose (0.02 mg/kg/injection) reversed cocaine conditioning-enhanced IL-6 and -decreased TNF-alpha levels in these brain regions. Nevertheless, such a memantine dosing regimen did not affect dopamine metabolism in mPFC and Acb. Single memantine (0.02 mg/kg) injection did not acutely affect mouse locomotor activity or cocaine-increased locomotor activity. Similar memantine dosing regimen was ineffective to affect the maintenance of cocaine-induced CPP. Finally, intra-mPFC infusion of recombinant IL-6, but not thalidomide, reversed memantine (0.02 mg/kg/injection x 6)-decreased cocaine-induced CPP. These results, taken together, suggest that cocaine conditioning-enhanced IL-6 in mPFC may be, in part, involved in the acquisition of cocaine-induced CPP. Moreover, an extremely low dose of memantine may decrease the acquisition of cocaine-induced CPP by reversing cocaine conditioning-increased IL-6 levels in mPFC. (C) 2011 Elsevier B.V. All rights reserved.
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