Adolescent nicotine potentiates the inhibitory effect of raclopride, a D2R antagonist, on phencyclidine-sensitized psychotic-like behavior in mice by Ana Carolina Dutra-Tavares instant download

Adolescent nicotine potentiates the inhibitory effect of raclopride, a D2R antagonist, on phencyclidine-sensitized psychotic-like behavior in mice by Ana Carolina Dutra-Tavares instant download

The association between schizophrenia and nicotine addiction becomes evident during adolescence. Here, to Keywords: investigate interactive events that might underlie the early establishment of this comorbidity, we used phencyclidine-evoked locomotor sensitization, a proxy model of psychotic behavior, and nicotine minipump Psychosis infusions in adolescent mice. Considering the involvement of dopamine D2 receptors in both schizophrenia and Positive symptoms addiction, we further tested their role by exposing mice to raclopride. Adolescent mice that were either exposed Tobacco to nicotine (24 mg/Kg/day) or not, received single daily raclopride (0.5 mg/kg, s.c.) or saline followed by Prodrome phencyclidine injections (10 mg/Kg, s.c.) during open field testing for 6 consecutive days (Acquisition phase, Adolescence ACQ). Phencyclidine and nicotine challenges (Sensitization Test, ST) were carried out after a 5-day withdrawal. Ambulation escalated in response to repeated phencyclidine exposure during ACQ and was increased after phencyclidine challenge, evidencing development and expression of locomotor sensitization. Raclopride prevented phencyclidine-evoked development of sensitization. However, raclopride pre-exposure during ACQ only shortened its expression in phencyclidine-challenged mice. Nicotine failed to interfere with phencyclidine stimulatory effects during ACQ but potentiated raclopride inhibition during the first ACQ days. During ST, nicotine history shortened the expression of phencyclidine-evoked sensitization. Nicotine challenge had no impact on locomotion, which is consistent with a lack of nicotine/phencyclidine cross-sensitization. In conclusion, our results show that nicotine does not worsen, and may even ameliorate phencyclidine-sensitized psychotic-like behavior in adolescent mice. The potentiation of raclopride-mediated inhibition further suggests that