Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex

Kuei Ying Lin, Chianfang G. Cherng, Fu Rong Yang, Li Ching Lin, Ru Band Lu, Lung Yu

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

Abstract

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-α) 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-α 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 × 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.

Original languageEnglish
Pages (from-to)126-131
Number of pages6
JournalBehavioural Brain Research
Volume220
Issue number1
DOIs
Publication statusPublished - 2011 Jun 20

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

Fingerprint

Dive into the research topics of 'Memantine abolishes the formation of cocaine-induced conditioned place preference possibly via its IL-6-modulating effect in medial prefrontal cortex'. Together they form a unique fingerprint.

Cite this