title: Varenicline disrupts prepulse inhibition only in high-inhibitory rats.
abstract: Varenicline, a widely used smoking cessation drug, has partial agonistic activity at α4β2 nicotinic receptors, and full agonistic activity at α7 nicotinic receptors. Thus it may interact with cognitive processes and may alleviate some of the cognitive disturbances observed in psychotic illnesses such as schizophrenia. We aimed to test the effects of varenicline on sensorimotor gating functioning, which is crucial for normal cognitive processes, especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. Prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning. First, the effects of varenicline and nicotine on rats having high or low baseline PPI levels were evaluated; then, varenicline was applied prior to apomorphine (0.5 mg/kg), and MK-801 (0.15 mg/kg), which are used as comparative models of PPI disruption. Varenicline (0.5-3 mg/kg) did not change PPI when given alone in naïve animals. When rats were selected according to their baseline PPI values, varenicline (1 mg/kg) significantly decreased PPI in high-inhibitory (HI) but not in low-inhibitory (LI) rats. Nicotine (1 mg/kg; tartrate salt) produced a similar activity in LI and HI groups. In combination experiments, varenicline did not reverse either apomorphine or the MK-801-induced disruption of PPI. These results demonstrate that the effects of both varenicline and nicotine on sensorimotor gating are influenced by the baseline PPI levels. Moreover, varenicline has no effect on apomorphine or the MK-801-induced disruption of PPI.
authors.affiliation: Department of Chest Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.
authors.forename: Tugba
authors.initials: T
authors.lastname: Goktalay
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Sema
authors.initials: S
authors.lastname: Buyukuysal
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey.
authors.forename: Gulsah
authors.initials: G
authors.lastname: Uslu
authors.affiliation: Department of Chest Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.
authors.forename: Aysin S
authors.initials: AS
authors.lastname: Coskun
authors.affiliation: Department of Chest Diseases, Faculty of Medicine, Celal Bayar University, Manisa, Turkey.
authors.forename: Arzu
authors.initials: A
authors.lastname: Yorgancioglu
authors.affiliation: Department of Medical Pharmacology, Psychopharmacology Research Unit, Gulhane Military Medical Academy, Ankara, Turkey.
authors.forename: Hakan
authors.initials: H
authors.lastname: Kayir
authors.affiliation: Neuropsychopharmacology Application and Research Center, Uskudar University, Istanbul, Turkey.
authors.forename: Tayfun
authors.initials: T
authors.lastname: Uzbay
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Uludag University, Bursa, Turkey. Electronic address: goktalay@gmail.com.
authors.forename: Gokhan
authors.initials: G
authors.lastname: Goktalay
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000162:Acoustics; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D065808:Prepulse Inhibition / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D000068580:Varenicline
chemical_list: D001552:Benzazepines; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D011810:Quinoxalines; D016291:Dizocilpine Maleate; D009538:Nicotine; D001058:Apomorphine; D000068580:Varenicline
keywords: Nicotine; Prepulse inhibition (PPI); Rat(s); Schizophrenia; Varenicline