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.

Neonatal quinpirole (NQ) treatment to rats increases dopamine D2 receptor sensitivity persistent throughout the animal’s lifetime. In Experiment 1, we analyzed the role of α7 and α4β2 nicotinic receptors (nAChRs) in nicotine behavioral sensitization and on the brain-derived neurotrophic factor (BDNF) response to nicotine in NQ- and neonatally saline (NS)-treated rats. In Experiment 2, we analyzed changes in α7 and α4β2 nAChR density in the nucleus accumbens (NAcc) and dorsal striatum in NQ and NS animals sensitized to nicotine. Male and female Sprague-Dawley rats were neonatally treated with quinpirole (1mg/kg) or saline from postnatal days (P)1-21. Animals were given ip injections of either saline or nicotine (0.5mg/kg free base) every second day from P33 to P49 and tested on behavioral sensitization. Before each injection, animals were ip administered the α7 nAChR antagonist methyllycaconitine (MLA; 2 or 4mg/kg) or the α4β2 nAChR antagonist dihydro beta erythroidine (DhβE; 1 or 3mg/kg). Results revealed NQ enhanced nicotine sensitization that was blocked by DhβE. MLA blocked the enhanced nicotine sensitization in NQ animals, but did not block nicotine sensitization. NQ enhanced the NAcc BDNF response to nicotine which was blocked by both antagonists. In Experiment 2, NQ enhanced nicotine sensitization and enhanced α4β2, but not α7, nAChR upregulation in the NAcc. These results suggest a relationship between accumbal BDNF and α4β2 nAChRs and their role in the behavioral response to nicotine in the NQ model which has relevance to schizophrenia, a behavioral disorder with high rates of tobacco smoking.