安全学习对大鼠中毒性伙伴效应的影响

目的探讨安全学习是否能阻碍中毒伙伴效应的形成,从而为有害动物防制提供有益的思路。方法实验用成年雄性Wistar大鼠24只,分为对照组、条件性味觉厌恶(CTA)组、安全学习组、观察学习组,其中,对照组单独饲养,其他3组饲养在具有三隔室的铁笼内以便相互作用;CTA组和安全学习组在摄取糖精溶液后,腹腔注射或者不注射LiCl使其分别建立对糖精的CTA和安全学习,观察学习组不做处理;两瓶法测定每只大鼠对糖精溶液相对摄取量。结果对照组、CTA组、安全学习组和观察学习组的糖精溶液嗜好比分别为65.18%、2.12%、86.78%和42.36%,各组之间的差异均具有统计学意义。结论安全学习能有效阻止中毒伙伴效应的发生。     

The NMDA receptor antagonist CPP impairs conditioned taste aversion and insular cortex long-term potentiation in vivo.

It has been proposed that long-term potentiation (LTP) a form of activity-dependent modification of synaptic efficacy, may be a synaptic mechanism for certain types of learning. Recent studies on the insular cortex (IC) a region of the temporal cortex implicated in the acquisition and storage of conditioned taste aversion (CTA), have demonstrated that tetanic stimulation of the basolateral nucleus of the amygdala (Bla) induce an N-methyl- -aspartate (NMDA) dependent LTP in the IC of adult rats in vivo. Here we present experimental data showing that intracortical administration of the NMDA receptor competitive antagonist CPP (-3(-2 carboxipiperazin-4-yl)-propyl-1-phosphonic acid) disrupts the acquisition of conditioned taste aversion, as well as, the IC-LTP induction in vivo. These findings are of particular interest since they provide support for the view that the neural mechanisms underlying NMDA dependent neocortical LTP, constitute a possible mechanism for the learning related functions performed by the IC.     

Paradoxical reinforcing properties of apomorphine: Effects of nucleus accumbens and area postrema lesions

Apomorphine (0.01–10.0 mg/kg, subcutaneously) paradoxically produced both dose-dependent aversive and positive reinforcing effects, as measured in conditioned taste aversion and place preference paradigms, respectively. The conditioned taste aversions produced by apomorphine were not modified in rats with bilateral 6-hydroxydopamine (6-OHDA) lesions of the nucleus accumbens (producing 92% depletion of dopamine in the nucleus accumbens) nor in rats with thermal lesions of the area postrema. Both types of lesions were behaviorally verified as effective in other paradigms; the 6-OHDA lesions potentiated the facilitatory effects of apomorphine on locomotor activity in photocell cages, and the area postrema lesions attenuated the conditioned taste aversions to a novel flavor paired with scopolamine methylnitrate (1.0 mg/kg, intraperitoneally). However, 6-OHDA lesions of the nucleus accumbens did clearly potentiate the conditioned place preferences induced by apomorphine. These results suggest that both the positive reinforcing and locomotor effects of apomorphine may partially result from activation of post-synaptic dopamine receptors in the nucleus accumbens. Moreover, the dissociation of apomorphine's aversive and positive reinforcing properties revealed by the 6-OHDA lesions may provide the first step in attempts to pinpoint the different brain sites of action where apomorphine produces its opposite motivational effects.     

Ethanol-induced CTA mediated by acetaldehyde through central catecholamine activity

The possible involvement of catecholamines (CA) in the mediation of acetaldehyde's conditioned taste aversion (CTA) was examined by testing the effects of alpha-methyl-para-tyrosine (AMPT, a tyrosine hydroxylase inhibitor) on the CTAs produced by acetaldehyde. AMPT blocked the acquisition of the CTA normally produced by a low dose of acetaldehyde (0.2 g/kg), but had no significant effect on CTA produced by a high dose of acetaldehyde (0.3 g/kg). In a second study, acetaldehyde's role in the CTA produced by ethanol was investigated using the pre-exposure conditioned taste aversion paradigm. Pre-exposure to acetaldehyde (both doses) blocked the ethanol CTAs but when pre-exposure with acetaldehyde was coupled with AMPT, only the larger dose of acetaldehyde blocked the ethanol aversion. These results suggest that while the CTA to the low dose of acetaldehyde may be primarily central and catecholamine-mediated, the mechanism underlying the high dose CTA is probably peripheral and emetic in nature. These findings support the conclusion that acetaldehyde may be mediating many of the actions of ethanol.     

Assessment of ethanol's hedonic effects in mice selectively bred for sensitivity to ethanol-induced hypothermia

Mice selectively bred for sensitivity (COLD) or insensitivity (HOT) to the hypothermic effect of ethanol were tested in three tasks purported to assess ethanol's hedonic properties: place conditioning, taste conditioning, and ethanol drinking. In the place conditioning task, distinctive tactile (floor) stimuli were differentially paired with injection of ethanol (2.25 g/kg) or saline, and preference for the tactile stimuli was assessed during a choice test without ethanol. In the taste conditioning task, fluid-deprived mice were given repeated access to saccharin followed by injection of ethanol (2.25 g/kg). In the drinking task, mice were given access on alternate days to a single drinking tube containing water or ethanol in a concentration that gradually increased from 1 to 12% (v/v) over days. HOT mice showed greater conditioned preference for ethanol-paired tactile cues, greater aversion for ethanol-paired flavor cues, and drank less ethanol at concentrations above 5% than COLD mice. HOT mice also showed higher levels of ethanol-stimulated activity than COLD mice. Control experiments indicated that the lines did not differ in initial preference for the tactile and flavor stimuli used in the conditioning tasks. Because the same line differences were seen in mice selected from two genetically independent populations, these studies offer strong evidence of genetic correlations between ethanol's thermal effect and its effect on activity, place conditioning and taste conditioning. Evidence of a genetic correlation between ethanol's thermal effect and ethanol drinking, however, is weaker since it is based on a line difference observed in only one of the genetic replicates. In general, these findings suggest commonality in the biological mechanisms underlying ethanol's thermal effect and its effect in each behavioral task. This overall pattern of genetic correlations might indicate that these tasks measure the same motivational effect of ethanol.     

On priority setting in preventive care resources

Using an expected utility approach, we show that within a population that differs with respect to the probability of developing a disease, the allocation of preventive care resources should be prioritized based on the efficiency of prevention and not on whether individuals are at high or low risk of developing the disease. Should the efficiency of prevention be the same within the population, we show that the gravity of the disease, the presence of co-morbidities and the existence of uncertainty on health status can alternatively be considered so as to prioritize among preventive care resources. Copyright © 2009 John Wiley & Sons, Ltd.     

呋喃唑酮厌恶疗法戒酒疗效观察

目的观察呋喃唑酮厌恶疗法戒酒的疗效和安全性。方法将90例酒精依赖患者随机分为厌恶治疗组和对照组,各45例,厌恶治疗组予呋喃唑酮厌恶疗法戒酒,对照组采取一般对症支持治疗,比较厌恶治疗组患者饮酒前后血压、脉搏、呼吸的变化。出院后随访1年,比较两组患者的戒酒成功率。结果呋喃唑酮厌恶疗法组患者的戒酒成功率高于对照组(P<0.05),并且呋喃唑酮厌恶疗法具有较好的安全性。结论呋喃唑酮厌恶疗法戒酒有较好的疗效和安全性。     

QALYs without bias? Nonparametric correction of time trade‐off and standard gamble weights based on prospect theory

Common health state valuation methodologies, such as standard gamble (SG) and time trade‐off (TTO), typically produce different weights for identical health states. We attempt to alleviate these differences by correcting the confounding influences modeled in prospect theory: loss aversion and probability weighting. Furthermore, we correct for nonlinear utility of life duration. In contrast to earlier attempts at correcting TTO and SG weights, we measure and correct all these tenets simultaneously, using newly developed nonparametric methodology. These corrections were applied to three less‐than‐perfect health states, measured with TTO and SG. We found considerable loss aversion and probability weighting for both gains and losses in life years, and we observe concave utility for gains and convex utility for losses in life years. After correction, the initially significant differences in weights between TTO and SG disappeared for all health states. Our findings suggest new opportunities to account for bias in health state valuations but also the need for further validation of resulting weights.