Nicotine Sensitization in β-Arrestin 2 Knockout Adolescent Mice.

Abstract

ß arrestin-2 is a protein involved in signaling of D2 receptors and plays a mediating role in sensitization to psychostimulants and the opiate morphine. In this study, 3-4 week old BA-2 KO and wild type C57/B6 mice received nicotine tartarate (s.c, 0.5 mg/kg free base) for 7 or 14 consecutive days followed by a drug-free period. An acute nicotine challenge followed the drugfree period. Results indicated that the absence of ß-arrestin-2 reduced sensitization to nicotine in Experiment 1. BA-2 KOs eventually demonstrated sensitization in Experiment 2. However, absence of ß-arrestin-2 blocked expression of sensitization on the challenge. After the challenge, brain tissue was removed and the nucleus accumbens was dissected and analyzed for brainderived neurotrophic factor (BDNF). Results showed that BDNF positively correlated with behavioral results. These results appear to indicate the importance of the ß-arrestin-2 protein in locomotor sensitization and that dopamine signaling is related to BDNF

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