Impaired Acquisition of Nicotine-Induced Conditioned Place Preference in Fatty Acid-Binding Protein 3 Null Mice

Wenbin Jia, Gofarana Wilar, Ichiro Kawahata, An Cheng, Kohji Fukunaga

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


Nicotine causes psychological dependence through its interactions with nicotinic acetylcholine receptors in the brain. We previously demonstrated that fatty acid-binding protein 3 (FABP3) colocalizes with dopamine D2 receptors (D2Rs) in the dorsal striatum, and FABP3 deficiency leads to impaired D2R function. Moreover, D2R null mice do not exhibit increased nicotine-induced conditioned place preference (CPP) following chronic nicotine administration. To investigate the role of FABP3 in nicotine-induced CPP, FABP3 knockout (FABP3−/−) mice were evaluated using a CPP apparatus following consecutive nicotine administration (0.5 mg/kg) for 14 days. Importantly, nicotine-induced CPP was suppressed in the conditioning, withdrawal, and relapse phases in FABP3−/− mice. To resolve the mechanisms underlying impaired nicotine-induced CPP in these mice, we assessed c-Fos expression and Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinase (ERK) signaling in both dopamine D1 receptor (D1R)- and D2R-positive neurons in the nucleus accumbens (NAc). Notably, 64% of dopamine receptor-positive neurons in the mouse NAc expressed both D1R and D2R. Impaired nicotine-induced CPP was correlated with lack of responsiveness of both CaMKII and ERK phosphorylation. The number of D2R-positive neurons was increased in FABP3−/− mice, while the number of D1R-positive neurons and the responsiveness of c-Fos expression to nicotine were decreased. The aberrant c-Fos expression was closely correlated with CaMKII but not ERK phosphorylation levels in the NAc of FABP3−/− mice. Taken together, these results indicate that impaired D2R signaling due to lack of FABP3 may affect D1R and c-Fos signaling and underlie nicotine-induced CPP behaviors.

Original languageEnglish
Pages (from-to)2030-2045
Number of pages16
JournalMolecular Neurobiology
Issue number5
Publication statusPublished - 2021 May


  • Ca/calmodulin-dependent protein kinase II
  • Dopamine D1 receptor
  • Dopamine D2 receptor
  • Fatty acid-binding protein 3
  • Nicotine-induced conditioned place preference

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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