Varenicline disrupts prepulse inhibition only in high-inhibitory rats.

Varenicline, a widely used smoking cessation drug, has partial agonistic activity at α4ß2 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.

Does high-frequency chest wall oscillation therapy have any impact on the infective exacerbations of chronic obstructive pulmonary disease? A randomized controlled single-blind study.

OBJECTIVE: To investigate the impact of high-frequency chest wall oscillation in chronic obstructive pulmonary disease patients with infective exacerbation. DESIGN: Clinical randomized controlled trial. SETTING: Patients received high-frequency chest wall oscillation therapy at the Department of Pulmonology. SUBJECTS: Stage III-IV chronic obstructive pulmonary disease patients hospitalized with acute infective exacerbation who had received high-frequency chest wall oscillation therapy were studied. INTERVENTIONS: Patients were randomized into two groups, which were classified as I and II. All patients have been treated with bronchodilators, antibiotics, if necessary oxygen and patient education, as part of acute chronic obstructive pulmonary disease exacerbation protocol. Group II patients received additional high-frequency chest wall oscillation therapy. MAIN MEASURES: Body mass index (B), forced expiratory volume in the first second (O), modified Medical Research Council dyspnea scale (D) and 6-minute walking test (E) (BODE) index, forced expiratory volume in the first second, dyspnea, exercise capacity, oxygenation parameters and hospitalization of duration were recorded at baseline and at three-days and five-days follow-up. RESULTS: From April 2009 to July 2011, a total of 99 patients were assessed for eligibility, 50 patients were enrolled and randomized into two groups. A total of 50 (100%) patients (25 in Group I and 25 in Group II) were followed up for five days. Application of high-frequency chest wall oscillation therapy resulted in no significant advantage in all outcomes (p > 0.05). Mean (SD) baseline BODE index value in Group I was 7.72 (1.76), in Group II was 7.72(1.89) (p = 0.55). On the fifth-day assessment, mean (SD) BODE index value in Group I was 7.24 (1.83), in group II was 6.44 (2.46) (p = 0.18). CONCLUSIONS: The application of high-frequency chest wall oscillation therapy offers no additional advantages on infective exacerbations in chronic obstructive pulmonary disease.