> Dissertation Defense Announcement
> To:  The George Mason University Community
>
> Candidate: Nachiket Dharker
> Program:    PhD Biosciences
>
> Date:   Wednesday August 8, 2012
> Time:   2:00 p.m.
> Place:  George Mason University
>            Occoquan Bldg., #203
>            Prince William Campus 
> <http://www.gmu.edu/resources/welcome/Directions-to-GMU.html>
>  
> Dissertation Director/Committee Chair: Dr. Karl J. Fryxell
> Committee members: Dr. Ancha Baranova, Dr. Daniel N. Cox, Dr. Timothy Born
>
> Title: "Gene Expression Responses to Single and Repeated Nicotine 
> Injections in Adolescent and Adult Mice"
>
> The dissertation is on reserve in the Johnson Center Library, Fairfax 
> campus.
> The doctoral project will not be read at the meeting, but should be 
> read in advance.
>
> All members of the George Mason University community are invited to 
> attend.
>
>
> *ABSTRACT:*
>
> The majority of smokers begin tobacco use during adolescence. 
> Relatively little is understood about the molecular effects of 
> nicotine on adolescents and its role in establishing future nicotine 
> dependence. Here we studied the mRNA expression of dopamine receptors 
> (Drd1, Drd2S, Drd2L, Drd3), cyclic nucleotide phosphodiesterases 
> [Pde4b (long isoforms), Pde4b1, Pde4d ], a tetraspanin (Cd81), opioid 
> peptides (Pdyn and Penk), and the anaplastic lymphoma kinase receptor 
> (Alk) after single or repeated nicotine injections in brain areas of 
> mice by quantitative reverse transcriptase PCR. We found that a single 
> nicotine injection caused dramatic gene expression responses in the 
> adolescent medial prefrontal cortex, where all inhibitory dopamine 
> receptor mRNAs (Drd2L, Drd2S, and Drd3) decreased by an average of 
> 3.5-fold after 24 hr in adolescents but not in adults. The 
> downregulation of Drd2 in adolescent males and females of the A/J and 
> C57BL/6J strains was strongly correlated (r = 0.99) with the nicotine 
> preference of those sexes and strains (measured as adults). More 
> generally, we found adolescent-specific gene expression responses to 
> nicotine in Drd2, Drd3, Pde4b (long isoforms), Alk, and Penk in medial 
> prefrontal cortex, and in Pde4b1 and Pde4d in ventral striatum. We 
> also found adolescent-specific sexually divergent gene expression 
> responses of Cd81. Another interesting finding was the significant 
> correlation between Drd2 and Penk expression in medial prefrontal 
> cortex (but not Drd1 and/or Pdyn). In contrast to the responses to a 
> single nicotine injection, repeated nicotine injections produced 
> significant gene expression responses for many of these genes in 
> ventral striatum that differed significantly between adolescents and 
> adults. In fact, the expression of Drd2S, and Drd2L decreased after 
> repeated nicotine injections in all adolescent sexes and strains, but 
> increased in most sexes and strains of adult ventral striatum. 
> Moreover, nicotine-induced changes in gene expression of all other 
> genes in ventral striatum were specific to adults. In medial 
> prefrontal cortex, fewer genes (Drd1 and Drd3) showed differential 
> gene expression responses between adolescents and adults, and none of 
> these gene expression responses were adolescent-specific. Our results 
> suggest that the initial adolescent-specific component of the gene 
> expression responses to nicotine occurs primarily in medial prefrontal 
> cortex, but the responses to repeated nicotine injections occur 
> primarily in ventral striatum. Results from other brain areas are also 
> reported. Our results help to elucidate several steps of 
> adolescent-specific gene expression response to nicotine by genes that 
> are implicated in drug abuse.
>
>  ###