Varenicline disrupts prepulse inhibition only in high-inhibitory rats

GÖKTALAY T., Buyukuysal S., Uslu G., ŞAKAR COŞKUN A., Yorgancioglu A., Kayir H., ...More

PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY, vol.53, pp.54-60, 2014 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 53
  • Publication Date: 2014
  • Doi Number: 10.1016/j.pnpbp.2014.03.001
  • Page Numbers: pp.54-60


Varenicline, a widely used smoking cessation drug, has partial agonistic activity at alpha 4 beta 2 nicotinic receptors, and full agonistic activity at alpha 7 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 naive 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. (C) 2014 Elsevier Inc. All rights reserved.