Exposição à nicotina durante a adolescência potencializa o efeito inibitório da racloprida, um antagonista do receptor D2, no comportamento semelhante à psicose induzido pela fenciclidina em camundongos

Abstract

Smoking has an association with patients with schizophrenia that begins in adolescence, with a common neural circuitry. In this project we investigated the biological basis of the association between schizophrenia and smoking. In order to this, we performed a pre- exposure to Nicotine in mice in the period of adolescence using a mini osmotic pump that released Nicotine until the end of the acquisition test. Then we evaluated the locomotor sensitization response to the Phencyclidine model of schizophrenia. Furthermore, we investigated the role of the dopaminergic system in behavioral sensitization by exposing animals to Raclopride, a D2 receptor antagonist. Adolescent mice exposed or not to nicotine (24mg/kg/day) were taken to an open field environment for 3 days of habituation (H1-3) and 6 days of testing (acquisition period AQ1-6). During the tests they received a single daily dose of Raclopride (0.5mg/kg, s.c.) or saline solution followed by injections of Phencyclidine (10mg/kg, s.c.). Sensitization tests were performed after a 5-day withdrawal. In this test, the animals received a challenge (D) of Phencyclidine or Nicotine. Ambulation increased in response to repeated Phencyclidine exposure during AQ and was increased after Phencyclidine challenge, evidencing the development and expression of locomotor sensitization. Raclopride prevented the development of Phencyclidine-evoked sensitization, but prior exposure during AQ only partially inhibited expression in Phencyclidine-challenged mice. Nicotine potentiated the inhibitory results of Raclopride during the first days of AQ and, during D, attenuated the expression of Phencyclidine- evoked sensitization. Nicotine challenge had no relevant impact on locomotion, which is consistent with the lack of cross-sensitization between Nicotine and Phencyclidine. In conclusion, our results showed that Nicotine does not worsen and may even improve Phencyclidine-sensitized psychotic behavior in adolescent mice. The results of the association of Nicotine with Raclopride showed that D2 receptors play a strong role in the actions of Phencyclidine and Nicotine