Nicotine sensitization and analysis of brain-derived neurotrophic factor in adolescent beta-arrestin-2 knockout mice.
Nicotine sensitization and levels of brain-derived neurotrophic factor (BDNF) were analyzed in adolescent beta-arrestin-2 knockout (betaA-2 KO) and wild type (WT) mice. The beta-arrestin-2 protein has been shown to be important in G-protein hydrolysis and receptor internalization. Four- to five-week-old adolescent betaA-2 KO and WT C57/Bl6 mice were administered either nicotine (0.5 mg/kg free base) or saline 10 min before being placed into a locomotor arena on each of 7 (Experiment 1) or 14 (Experiment 2) consecutive days. A nicotine challenge was given 7 days after sensitization was complete. In Experiment 1, betaA-2 KO mice administered nicotine or saline and WT mice administered nicotine demonstrated significant hypoactivity during early in testing, and neither WT nor betaA-2 KO mice administered nicotine demonstrated sensitization. On the nicotine challenge, WT mice administered nicotine demonstrated significantly higher activity levels compared to all groups, and this same group demonstrated significantly higher levels of accumbal BDNF compared to all groups. In Experiment 2, betaA-2 KO mice were again hypoactive compared to WT mice, whereas WT mice administered nicotine demonstrated significant hypoactivity during initial testing and significantly higher levels of activity compared to all other groups late in testing. On the nicotine challenge, WT mice that received nicotine demonstrated a significant increase in activity compared to all groups, and showed increased accumbal BDNF compared to all groups. These results show that the beta-arrestin-2 protein is important in induction and expression of nicotine sensitization as well as nicotine's effects on accumbal BDNF.
Correll
Jennifer A
JA
Department of Psychology, East Tennessee State University, Johnson City, Tennessee 37614, USA.
Noel
Daniel M
DM
Sheppard
A Brianna
AB
Thompson
Kimberly N
KN
Li
Yi
Y
Yin
Deling
D
Brown
Russell W
RW
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019390:Arrestins / Q000235:genetics*; D001923:Brain Chemistry / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins
C000605258:Arrb2 protein, mouse; D019390:Arrestins; D019208:Brain-Derived Neurotrophic Factor; D018722:Nicotinic Agonists; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D009538:Nicotine