Increased and decreased preference for saccharin immediately following injections of various agents

Rats pretrained for preference testing and injected with LiCl showed a reduction of saccharin preference in a test with a novel saccharin solution paired with water given 15 min following the injection. Previous exposure to the saccharin solution precluded this selective depression of drinking. In a second experiment, using rats naive to saccharin, insulin injection produced an increase, 2-DG and hypertonic NaCl produced a decrease, and saccharin injection produced no change in saccharin preference.     

Septal lesion and experiential influences on saline and saccharin preference-aversion functions

Relatively high (unpalatable) concentrations of saline or saccharin (independent studies) presented in 24 hr choices with water were found to more markedly and persistently suppress the subsequent preference of septal-lesioned rats for lower concentrations when compared with any such shifts in preference displayed by operated-control rats. These data were used to support the notion that the septal region is involved with a comparator mechanism which affects the animal's response to various external and internal cues guiding consumption. In addition, wide individual differences in both groups were presented and discussed to emphasize that future studies should be designed to clarify those uncontrolled genetic and/or early experience variables which must serve, at least in part, to differentially bias the adult animal's consummatory choice behavior.     

Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor,Goe 5438

The effect of the novel 1,4-dihydronaphthyridine Ca²⁺ channel inhibitor Goe 5438 (CI-951) on voluntary ethanol consumption was examined in selectively bred alcohol-preferring (P) rats in a free choice two bottle preference test versus water. Intraperitoneally injected Goe 5438 dose-dependently (5, 10 or 20 µmol/kg, twice daily) inhibited ethanol and increased water intake over the 24 h period (injection day). The drug decreased ethanol preference, originally above 90%, by 6%, 19% and 45% at respective doses, on the injection day. That inhibitory effect of the highest dose of Goe 5438 on ethanol preference remained significant also on days 2 and 3 after injections (–51% and –18%, respectively). Goe 5438, in the highest dose, also tended to decrease granulated chow consumption during the injection day only. To further test whether the inhibition of ethanol preference is secondary to decrease in reinforcing properties of ethanol and not due to interference with satiety mechanisms, we compared the effect of two higher doses (10 and 20 µmol/kg, intraperitoneally, twice daily) of Goe 5438 on spontaneous preference for a non-caloric 0.04% saccharin solution in Sprague-Dawley rats. We observed a dose-dependent suppression of preference (by 44% and 58%, respectively) during the injection day, but not the subsequent 24 h period. However, Goe 5438 also significantly alleviated food pellet intake on the injection day. In conclusion, Goe 5438 produces potent and long-lasting inhibition of voluntary ethanol consumption, which may be secondary to attenuation of reinforcing properties of ethanol. Additionally, this particular Ca²⁺ channel inhibitor appears to have mild anorectic properties which may be conducive to acute suppression of alcohol intake.     

Voluntary consumption of morphine in 15 inbred mouse strains

To determine genetic differences in voluntary morphine consumption, 15 commonly used inbred strains of mice were given ad libitum two-bottle choice between saccharin alone or saccharin/morphine in one bottle and water in the other bottle. Subsequently, the saccharin was gradually reduced to zero, leaving only morphine. Independent groups of mice of the same strains were exposed to quinine in a parallel manner to control for the bitter alkaloid taste of morphine. Of the 15 strains, the C57BL/6J strain showed the highest consumption of morphine, both with or without saccharin and greatest consumption of morphine relative to quinine; it also showed only a slight decline in fluid consumption when morphine was added to the saccharin bottle. In marked contrast, the SWR/J strain showed the least consumption of morphine by the same criteria, followed closely by the AKR/J, CE/J, DBA/2J and SJL/J strains. The strain differences for all the morphine drinking measures exceeded an order of magnitude. Strain-specific voluntary morphine/saccharin consumption was not significantly correlated with saccharin consumption alone, but was highly correlated with morphine consumption alone. The results show that these behaviors are under an unusually large degree of genetic determination, and some of the largest strain differences remained essentially the same regardless of whether saccharin was present, or whether quinine was used as a control tastant.     

The taste aversion induction properties of two long duration barbiturates

The ability of sodium phenobarbital (60 mg/kg) and sodium barbital (80 mg/kg) to produce a taste aversion in 23 hr fluid deprived rats was examined using a discrimination or two bottle taste aversion task (0.125% sodium saccharin solution or water). The interaction of both barbiturates with the effects of 3.0 mEq/kg lithium chloride (LiCl) was also examined. Results indicate that phenobarbital treatment alone produces a stronger saccharin aversion than does barbital. Also, barbiturate treatment 24 hr after LiCl administration does not attenuate saccharin avoidance, although phenobarbital treatment following LiCl administration was sufficient to induce a maximum aversion that did not extinguish after twenty days of continuous discrimination testing. These data suggest that the aversion inducing properties of the two barbiturates are dissimilar and that phenobarbital is the more effective agent in the production of saccharin aversion. In addition, barbiturate induced attenuation of conditioned taste aversion is apparently related to the periodic forced intake test model since it does not occur when a water and saccharin choice is available.     

Concurrent self-administration of ethanol and an alternative nondrug reinforcer in monkeys: effects of income (session length) on demand for drug

Eight rhesus monkeys (Macaca mulata) were trained to self-administer orally delivered ethanol (8%) and saccharin (0.03 or 0.3% wt/vol) or water under concurrent fixed-ratio (FR) schedules. The FR requirement for saccharin was fixed at 32, while the FR for ethanol was varied (4, 8, 16, 32, 64 and 128) in a nonsystematic order to assess demand for drug. Demand was defined as consumption plotted as a function of price (FR). Income was defined as the duration of access to available resources. Income was varied by allowing access to the concurrently available liquids 20, 60 or 180 min per day. Order of testing was counter-balanced across monkeys. Saccharin deliveries were much higher than ethanol deliveries under the 180-min income condition; however, they were lower than ethanol deliveries when income was reduced to 20 min and the ethanol FR was 4, 8 or 16. Thus, when the price of drug was relatively low, consumption of drug exceeded that of the nondrug reinforcer, and that relationship was reversed as income decreased. Saccharin deliveries sustained a proportionally greater reduction due to decreased income compared to ethanol deliveries. As income decreased from 180 to 20 min, saccharin deliveries were reduced by an average of 79.1% (across ethanol FR conditions) while ethanol deliveries were reduced by an average of 41.2 and 40.8% when concurrent saccharin or water were available, respectively; thus, drug self-administration was more resistant to income changes than saccharin. The demand for ethanol was shifted downward in a parallel fashion as income decreased. As ethanol cost (FR) increased, there were proportionately greater decreases in ethanol intake when saccharin was concurrently available compared to when water was available. There was a 35–50% reduction in ethanol deliveries due to concurrent saccharin (versus water) at FR 4, compared to a 55–75% reduction at FR 128. Cost of ethanol (FR), income level and the availability of a nondrug reinforcer are all variables that modify ethanol-reinforced behavior, and income alters the relative preference for a drug versus nondrug reinforcer.     

Acquisition of oral phencyclidine (PCP) self-administration in rhesus monkeys: effects of dose and an alternative non-drug reinforcer

 The effects of drug dose and a non-drug alternative reinforcer on acquisition of oral PCP self-administration in rhesus monkeys were examined. Acquisition was studied using three groups of monkeys (seven subjects per group). One group received a low PCP dose (0.0375 mg/delivery) and the other two received a high PCP dose (0.15 mg/delivery). One of the high dose groups had concurrent access to a saccharin solution (0.03% w/v) and water during the intersession (17.5-h) period. Food non-restricted monkeys were initially given access to water under a fixed-ratio (FR) 1 schedule during daily 3-h sessions. Water was then replaced with PCP during the session. The monkeys were then reduced to 85% of their free-feeding body weights and fed before the session, and the FR value was increased from 1 to 2, 4 and 8. Subsequently, food was given post-session and water and PCP were available under concurrent FR 8 schedules. At this final step of the procedure, acquisition of PCP self-administration was considered to occur if PCP intake consistently exceeded water intake. When all three groups were given concurrent access to PCP and water, PCP intake was greater than water intake only in the group of monkeys receiving the high PCP dose. PCP intake increased when water replaced saccharin during intersession in the high PCP dose group. Within-group data revealed that 85.7% of monkeys acquired PCP reinforcement in the group given access to the high PCP dose while only 42.8% acquired in the other two groups. These data suggest that drug dose and presence of alternative non-drug reinforcers affect acquisition of drug self administration in non-human primates. Received: 14 May 1997 / Final version: 15 December 1997     

Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina

OBJECTIVE: To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina. METHODS: Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT. RESULTS: Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term (> or =10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use. CONCLUSION: Regular use of AS for 10 years or more was positively associated with UTT.     

儿童鼻粘膜纤毛传输功能的研究

目的：研究儿童鼻粘膜纤毛传输功能及麻黄素滴鼻剂对儿童鼻粘膜纤毛传输功能的影响。方法：任意抽选5－10岁、11－16岁正常儿童各59例，并对后者行1％呋喃滴鼻剂每日3次、每次2滴滴鼻，持续10d和停药1月后分别进行糖精实验；鼻病组（变应性鼻炎59例、慢性鼻鼻窦炎62例）也分别用糖精法测定鼻粘膜纤毛输送率（MTR）。结果：呋嘛滴鼻组与慢性鼻窦炎组与正常组比较P＜0．01，差别有显著性意义；变态反应组与正常组比较P＞0．05，呋嘛滴鼻组停药后与正常组比较P＞0．05，无显著性差异。结论：麻黄素类鼻腔粘膜局部减充血剂持续使用10d，对鼻腔纤毛功能造成可逆性损害；精法测量MTR可作为儿童鼻粘膜病变严重程度的评定的客观指标。     

Improvement of sinonasal mucociliary function by endoscopic sinus surgery in patients with chronic rhinosinusitis

Objectives

Mucociliary clearance is an important defense mechanism for upper and lower airway. Chronic rhinosinusitis has been frequently associated with mucociliary dysfunction. Endoscopic sinus surgery (ESS) is recommended for treatment-resistant sinusitis in order to improve mucociliary function. The present study investigated the effect of ESS on the saccharin time (mucociliary clearance time) in relation to symptom profile assessed by the Sino-nasal Outcome Test (SNOT)-22, and disease severity based on the Lund-Kennedy endoscopic scores and Lund-Mackay computed tomographic (CT) scores.