The effects of adulthood nicotine treatment on D2-mediated behavior and neurotrophins of rats neonatally treated with quinpirole.

This study was designed to analyze the effects of nicotine on yawning behavior and neurotrophin content in the hippocampus and frontal cortex of D2-receptor primed female adult Sprague-Dawley rats. Animals were neonatally treated with quinpirole, a dopamine (DA) D2/D3 agonist, from postnatal day 1-21 (P1-21) and raised to P60 and administered nicotine tartarate (0.3 mg/kg free base) or saline twice daily for 14 days. One day after nicotine treatment had ceased, the number of yawns was recorded for 1 h in response to an acute injection of quinpirole (i.p., 100 microg/kg). Yawning is a D2-receptor mediated event. D2-primed rats demonstrated a significant increase in yawning in response to acute quinpirole compared with that of controls, but nicotine did not alleviate this effect. Neonatal quinpirole treatment produced a significant decrease of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the hippocampus that was alleviated by adulthood nicotine treatment. Interestingly, nicotine treatment to controls produced a significant increase of NGF in the frontal cortex, but a significant decrease of both NGF and BDNF in the hippocampus and BDNF in the frontal cortex. The decreases shown in NGF and BDNF is contrary to past findings that have shown nicotine to produce significant increases of hippocampal NGF and BDNF, but these past studies utilized male rats or mice or were performed in vitro. This study shows that nicotine has complex interactions with NGF and BDNF in D2-primed and control animals, and emphasizes the importance of gender differences when analyzing nicotine's effects on neurotrophins.