Voluntary oral nicotine intake in mice down-regulates GluR2 but does not modulate depression-like behaviors.
Repeated exposure to nicotine induces adaptive changes in the central nervous system including the mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). These modifications can modulate nicotine reward and reinforcement, but also anxiety and depression-related behaviors. The development of addiction-related phenotypes is known to be modulated by regulation of glutamate receptors, as well as activation of transcription factors including cAMP response element-binding protein (CREB), in the NAc. We investigated the effects of nicotine pre-exposure on nicotine preference and levels of GluR1/2 and CREB in the mesolimbic system in male mice C57BL/6J and BALB/c inbred mice. We also evaluated locomotor activity, anxiety-like and depression-like behaviors known to be affected by nicotine. There were few behavioral changes in mice subjected to chronic nicotine exposure, but there was a marked regulation of GluR2 in the mesolimbic system. Both treated and non-treated animals showed a significant preference for nicotine when facing a choice with a control solution. These results suggest that voluntary nicotine drinking induces nicotine preference in mice, but does not alter a number of affective behaviors. In addition, alterations in CREB and GluR1 levels are not sufficient to explain preference for nicotine in a 2-bottle choice paradigm.
Vieyra-Reyes
Patricia
P
Yale University, Department of Psychiatry, 34 Park Street, New Haven, CT 06508, USA.
Picciotto
Marina R
MR
Mineur
Yann S
YS
D000284:Administration, Oral; D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D012201:Reward; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014029:Tobacco Use Disorder / Q000378:metabolism* / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism; D014836:Volition / Q000187:drug effects / Q000502:physiology
C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D018722:Nicotinic Agonists; D018091:Receptors, AMPA; D018698:Glutamic Acid; D009538:Nicotine; C104722:glutamate receptor ionotropic, AMPA 2