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.

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SUMMARY It has been suggested that one risk factor in the development of hypertension and vascular disease may be abnormal copper and zinc metabolism. In the current study we tested the hypothesis that hypertension itself may result in alterations in the metabolism of these essential elements. Dahl salt-sensitive rats were fed diets containing 0.4 or 8.0% NaCl for 32 days. At the conclusion of the study, blood pressure was significantly higher in the rats fed a high NaCl diet than in controls. Liver, kidney, and heart copper concentrations were significantly lower in the rats fed a high NaCl diet compared with controls, while plasma copper levels were higher. In contrast, tissue zinc levels were higher in the rats fed a high NaCl diet than in controls, while plasma zinc levels were lower. It is hypothesized that alterations in copper and zinc metabolism may be one factor underlying tissue damage in these animals. (Hypertension 9: 624-628, 1987)

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To determine whether age-related changes in salt preferences occur over the lifespans of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY), the same animals of each genotype were tested as juveniles, and as young and older adults. Taste preference ratios for NaCl and KCl, at concentrations from 0.001 to 1.0 M, were calculated using 24-hour, two-bottle preference tests of each salt versus distilled water. Genotype exerted a significant effect on preference for both NaCl and KCl (p less than 0.0005). At each age and across concentrations, SHR had consistently higher preferences than did WKY. Few marked, age-related changes in overall preference for NaCl were noted within either strain, but juvenile and older adult SHR and WKY exhibited stronger preferences than did young adults for the higher concentrations of NaCl below the rejection threshold (p less than 0.001). Statistical age by concentration preference trends for KCl were similar to those for NaCl in SHR. Young adult WKY, however, had a significantly lower rejection threshold for that compound than did juveniles and older adults (p less than 0.001). These results indicate that genotype, age, salt type, and salt concentration can interact to influence salt preference in hypertension.

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