title: Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats.
abstract: The prevalence of tobacco smoking in HIV-1 positive individuals is 3-fold greater than that in the HIV-1 negative population; however, whether HIV-1 viral proteins and nicotine together produce molecular changes in mesolimbic structures that mediate psychomotor behavior has not been studied. This study determined whether HIV-1 viral proteins changed nicotine-induced behavioral sensitization in HIV-1 transgenic (HIV-1Tg) rats. Further, we examined cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the prefrontal cortex (PFC), nucleus accumbens (NAc) and ventral tegmental area (VTA). HIV-1Tg rats exhibited a transient decrease of activity during habituation, but showed attenuated nicotine (0.35mg/kg, s.c.)-induced behavioral sensitization compared to Fisher 344 (F344) rats. The basal levels of phosphorylated CREB and ERK2 were lower in the PFC of HIV-1Tg rats, but not in the NAc and VTA, relative to the controls. In the nicotine-treated groups, the levels of phosphorylated CREB and ERK2 in the PFC were increased in HIV-1Tg rats, but decreased in F344 animals. Moreover, repeated nicotine administration reduced phosphorylated ERK2 in the VTA of HIV-1Tg rats and in the NAc of F344 rats, but had no effect on phosphorylated CREB, indicating a region-specific change of intracellular signaling. These results demonstrate that HIV-1 viral proteins produce differences in basal and nicotine-induced alterations in CREB and ERK signaling that may contribute to the alteration in psychomotor sensitization. Thus, HIV-1 positive smokers are possibly more vulnerable to alterations in CREB and ERK signaling and this has implications for motivated behavior, including tobacco smoking, in HIV-1 positive individuals who self-administer nicotine.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Narasimha M
authors.initials: NM
authors.lastname: Midde
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Gomez
authors.forename: Steven B
authors.initials: SB
authors.lastname: Harrod
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000187:drug effects*; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D015658:HIV Infections / Q000503:physiopathology / Q000523:psychology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D006185:Habituation, Psychophysiologic; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction; D012907:Smoking / Q000503:physiopathology / Q000523:psychology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000503:physiopathology
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D054298:Human Immunodeficiency Virus Proteins; D009538:Nicotine