Clozapine Inhibits Development and Expression of Nicotine-Induced Locomotor Sensitization in Rats


Kayir H., GÖKTALAY G., Yildirim M., Uzbay T. I.

SYNAPSE, cilt.63, sa.1, ss.15-21, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 63 Sayı: 1
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1002/syn.20576
  • Dergi Adı: SYNAPSE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.15-21
  • Anahtar Kelimeler: clozapine, locomotor sensitization, nicotine, substance dependence, rat(s), INDUCED BEHAVIORAL SENSITIZATION, INCENTIVE-SENSITIZATION, ANTIPSYCHOTIC-DRUGS, RECEPTOR ANTAGONIST, COGNITIVE FUNCTION, NUCLEUS-ACCUMBENS, DOPAMINE RELEASE, SUBSTANCE-ABUSE, NITRIC-OXIDE, SCHIZOPHRENIA
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

It has been shown that clozapine, the prototype of atypical antipsychotics, significantly reduces daily cigarette use and alcohol consumption in schizophrenic patients. However, our knowledge about the effect of clozapine on nicotine abuse is limited. Aim of this study was to determine whether clozapine would inhibit the development and expression of nicotine-induced locomotor sensitization in rats. To investigate the effect of clozapine on the development of nicotine-induced locomotor sensitization, rats were pretreated with clozapine (2.5-10 mg/kg) 30 min before the nicotine (0.5 mg/kg), and locomotor activity was recorded for 15 min. This procedure was repeated every day for eight sessions. After a 3-day drug-free period, rats were challenged with nicotine (0.5 mg/kg). To reveal effect of clozapine on the expression of nicotine-induced locomotor sensitization, rats were injected with nicotine for eight sessions. After a 3-day drug-free period, rats were pretreated with clozapine (2.5-10 mg/kg) or vehicle 30 min before the nicotine (0.5 mg/kg) challenge injection. Repeated administration or nicotine generated robust locomotor sensitization in rats. Clozapine pretreatment (2.5-10 mg/kg) blocked the development and the expression of nicotine-induced locomotor sensitization in rats. Our results suggest that atypical antipsychotic clozapine can prevent the effects of nicotine in an animal model of dependence, which represents early adaptations in initiation and continuation of addictive behavior. Synapse 63:15-21, 2009. (C) 2008 Wiley-Liss, Inc.