The kinetics of inhibition by amiloride of the integrated chorda tympani response were investigated in rats subjected to lingual stimulation with NaCl. In one series of experiments the time of exposure to amiloride was varied at fixed amiloride concentration. Exposure to 10(-4) M amiloride for 2 s reduced the response to 0.5 M NaCl by approximately 50%. The time course of recovery from amiloride inhibition was first order (relaxation time approximately equal to 4 min) for all exposure times. For exposure to 10(-4) M amiloride for less than or equal to 30 s recovery was better than 90% in 20 min. Not all of the chorda tympani response was inhibited by amiloride. With 0.5 M NaCl there was a 70% reduction in response, whereas at 0.05 M NaCl the reduction was only 30%. Parallel effects of amiloride were seen in the short-circuit current of an in vitro preparation of canine lingual epithelium. Amiloride reduced the short-circuit current by the same percentage as it inhibited the chorda tympani response. These results suggest that gustatory transduction is mediated in part by an apical membrane transport system that can be inhibited by amiloride. There exists, however, a second transducing element that is amiloride insensitive. A model is developed, assuming, in part, that the neural response reflects the flows of Na through amiloride-sensitive apical pathways.

Research Methods and Procedures:This was an intervention study that used a volunteer sample of 70 healthy, sedentary men (n ϭ 29) and postmenopausal women (n ϭ 41) 50 to 75 years of age, with a BMI Յ37 kg/m 2 , from the Washington, DC, metropolitan area. Participants completed 6 weeks of dietary stabilization (American Heart Association diet) before 24 weeks of supervised aerobic exercise training. Diet was maintained throughout the intervention. Change in percent total body fat, percent trunk fat, and fat mass by DXA in ADR genotype groups (Glu 12 /Glu 9 ␣2b-ADR, Trp64Arg ␤3-ADR, and Gln27Glu ␤2-ADR) at baseline and after 24 weeks of aerobic exercise training was measured.Results: In multivariate analysis (covariates: age, gender, and baseline value of phenotype), best fit models for percent total body and trunk fat response to exercise training retained main effects of all three ADR gene loci and the effects of each gene-gene interaction (p ϭ 0.009 and 0.003, respectively). Similarly, there was a trend for the fat mass response model (p ϭ 0.03). The combined genetic factors explained 17.5% of the overall model variability for percent total body fat, 22% for percent trunk fat, and 10% for fat mass. Discussion: The body fat response to exercise training in older adults is associated with the combined effects of the Glu 12 /Glu 9 ␣2b-, Trp64Arg ␤3-, and Gln27Glu ␤2-ADR gene variants and their gene-gene interactions.

Patients with social phobia who responded well to 6 months of open-label treatment with clonazepam were assigned to receive either continuation treatment (CT) with clonazepam for another 5 months, or to undergo discontinuation treatment (DT) using a clonazepam taper at the rate of 0.25 mg every 2 weeks, with double-blind placebo substitution. Clinical efficacy was compared between the CT and DT groups using three different social phobia scales. Benzodiazepine withdrawal symptoms were also measured. Relapse rates were 0 and 21.1% in the CT and DT groups, respectively. Subjects in the CT group generally showed a more favorable clinical response at midpoint and/or endpoint, although even in the DT group clinical response remained good. With respect to withdrawal symptoms, the rates were low in both groups (12.5% for CT and 27.7% for DT) with no real evidence suggesting significant withdrawal difficulties. At the end of 11 months of treatment with clonazepam, however, a more rapid withdrawal rate was associated with greater distress. This study offers preliminary evidence to suggest that continuation therapy with clonazepam in the treatment of social phobia is safe and effective, producing a somewhat greater clinical benefit than a slow-taper discontinuation regime. However, even in the DT group, withdrawal symptoms were not found to be a major problem. The study can be taken as supportive of benefit for longterm clonazepam treatment in social phobia, as well as being compatible with a reasonably good outcome after short-term treatment and slow taper.