Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat

Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh) form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH). MCH promotes feeding behavior via MCH receptor-1 (MCH1R) in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding

PReVENT - protective ventilation in patients without ARDS at start of ventilation: study protocol for a randomized controlled trial

Background It is uncertain whether lung-protective mechanical ventilation using low tidal volumes should be used in all critically ill patients, irrespective of the presence of the acute respiratory distress syndrome (ARDS). A low tidal volume strategy includes use of higher respiratory rates, which could be associated with increased sedation needs, a higher incidence of delirium, and an increased risk of patient-ventilator asynchrony and ICU-acquired weakness. Another alleged side-effect of low tidal volume ventilation is the risk of atelectasis. All of these could offset the beneficial effects of low tidal volume ventilation as found in patients with ARDS. Methods/Design PReVENT is a national multicenter randomized controlled trial in invasively ventilated ICU patients without ARDS with an anticipated duration of ventilation of longer than 24 hours in 5 ICUs in The Netherlands. Consecutive patients are randomly assigned to a low tidal volume strategy using tidal volumes from 4 to 6 ml/kg predicted body weight (PBW) or a high tidal volume ventilation strategy using tidal volumes from 8 to 10 ml/kg PBW. The primary endpoint is the number of ventilator-free days and alive at day 28. Secondary endpoints include ICU and hospital length of stay (LOS), ICU and hospital mortality, the incidence of pulmonary complications, including ARDS, pneumonia, atelectasis, and pneumothorax, the cumulative use and duration of sedatives and neuromuscular blocking agents, incidence of ICU delirium, and the need for decreasing of instrumental dead space. Discussion PReVENT is the first randomized controlled trial comparing a low tidal volume strategy with a high tidal volume strategy, in patients without ARDS at onset of ventilation, that recruits a sufficient number of patients to test the hypothesis that a low tidal volume strategy benefits patients without ARDS with regard to a clinically relevant endpoin

Decision making in interhospital transport of critically ill patients: national questionnaire survey among critical care physicians

Objective: This study assessed the relative importance of clinical and transport-related factors in physicians' decision-making regarding the interhospital transport of critically ill patients. Methods: The medical heads of all 95 ICUs in The Netherlands were surveyed with a questionnaire using 16 case vignettes to evaluate preferences for transportability; 78 physicians (82%) participated. The vignettes varied in eight factors with regard to severity of illness and transport conditions. Their relative weights were calculated for each level of the factors by conjoint analysis and expressed in beta. The reference value (beta = 0) was defined as the optimal conditions for critical care transport; a negative beta indicated preference against transportability. Results: The type of escorting personnel (paramedic only: beta = 3.1) and transport facilities (standard ambulance beta = 1.21) had the greatest negative effect on preference for transportability. Determinants reflecting severity of illness were of relative minor importance (dose of noradrenaline beta = 0.6, arterial oxygenation beta = 0.8, level of peep beta = 0.6). Age, cardiac arrhythmia, and the indication for transport had no significant effect. Conclusions: Escorting personnel and transport facilities in interhospital transport were considered as most important by intensive care physicians in determining transportability. When these factors are optimal, even severely critically ill patients are considered able to undergo transport. Further clinical research should tailor transport conditions to optimize the use of expensive resources in those inevitable road trip

Unidirectional relationship between heroin self-administration and impulsive decision-making in rats

Rationale: There is growing clinical evidence for a strong relationship between drug addiction and impulsivity. However, it is not fully clear whether impulsivity is a pre-existing trait or a consequence of drug abuse. Recent observations in the animal models show that pre-existing levels of impulsivity predict cocaine and nicotine seeking. Whether such relationships also exist with respect to non-stimulant drugs is largely unknown. Objective: We studied the relationship between impulsive choice and vulnerability to heroin taking and seeking. Materials and methods: Rats were selected in the delayed reward task based on individual differences in impulsive choice. Subsequently, heroin intravenous self-administration behaviour was analysed, including acquisition of heroin intake, motivation, extinction and drug- and cue-induced reinstatement. Throughout the entire experiment, changes in impulsive choice were monitored weekly. Results and discussion: High impulsivity did not predict measures of heroin taking. Moreover, high impulsive rats did not differ from low impulsive rats in extinction rates or heroin- and cue-induced reinstatement. However, both groups became more impulsive as heroin self-administration continued. During abstinence, impulsivity levels returned towards baseline (pre-heroin) levels. Our results indicate that, in contrast to psychostimulants, impulsive choice does not predict vulnerability to heroin seeking and taking. Conclusion: These data implicate that different neural mechanisms may underlie the vulnerability to opiate and psychostimulant dependence. Moreover, our data suggest that elevated impulsivity levels as observed in heroin-dependent subjects are a consequence of heroin intake rather than a pre-existing vulnerability trait. © 2011 The Author(s)

The reliability and validity of a new and simple method to measure sedation levels in intensive care patients: a pilot study

BACKGROUND: Since more sophisticated ventilation techniques have enabled patients to comply with the ventilator with little or no sedation, deep sedation levels can easily be avoided. However, successful ventilation techniques also expanded the treatment possibilities for more severely ill patients who require deeper sedation levels. We developed a new sedation score to improve the prevention of oversedation and to simplify scoring practice in the intensive care unit (ICU). OBJECTIVE: The study's objective was to establish the validity and reliability of a new sedation score (Sedic score) for critically ill, sedated adult patients. METHODS: We prospectively evaluated the reliability and validity of the Sedic score. The study took place in a 30-bed ICU in a university teaching hospital. Forty-six consecutive mechanically ventilated and sedated ICU patients were included. The constructed scale consists of five levels of stimuli and five levels of responses. Sedation levels are defined by the sum of stimulus and response. The reliability of the Sedic score was assessed by simultaneous measurement by the research nurse and attending nurse (n=70). Validity was expressed as (1) the hierarchic relation between stimulus and response (n=443), (2) the prediction of wake-up time by the Sedic score (n=46), and (3) the association between the Sedic score and the Ramsay scale (n=88). RESULTS: The method showed excellent reliability. Validity: Weighted kappa between stimulus and response was .82. Multivariate analysis: (recovery time as independent variable) regression line (Y=-2.53+ 2.16 * beta; P <.001) (r2=42%). Correlation between the Sedic scores and the Ramsay scores was r(s) .74 (P=.01). Sixty-seven percent of the patients with a maximum Ramsay score of 6 had scores ranging between 6 and 10 on the Sedic scale, indicating that the Ramsay scale has a serious ceiling effect. CONCLUSION: The Sedic score demonstrates sufficient reliability and validity, and correlates well with wake-up time. It allows for frequent use by nurses to avoid oversedation in patient

Cannabinoid modulation of the reinforcing and motivational properties of heroin and heroin-associated cues in rats

RATIONALE: Recently, we provided evidence for a cannabinoid mechanism in relapse to cocaine seeking in rats. There is also increasing evidence for functional cross-talk between cannabinoid and opioid systems in several physiological processes. OBJECTIVES: This study was designed to evaluate whether the cannabinoid system plays a role in mediating the reinforcing and motivational effects of heroin and heroin-paired stimuli. METHODS: Male Wistar rats were trained to self-administer heroin (50 microg/kg per infusion) on fixed (FR5) or progressive ratio schedules of reinforcement in the presence of a discriminative and discrete heroin-associated cue. The selective cannabinoid CB1 antagonist SR141716A was given 30 min before the session to determine its effect on responding for heroin. Separate groups of rats were subjected to extinction training during which heroin-associated cues were absent and no heroin was delivered. During subsequent reinstatement tests, the effects of the cannabinoid agonist HU210 and the antagonist SR141716A on reinstatement of heroin seeking were evaluated. RESULTS: The cannabinoid antagonist dose-dependently reduced responding for heroin on the FR5 schedule and to a greater extent on the progressive ratio schedule. HU210 (20 microg/kg) reinstated heroin seeking behaviour following a 2-week extinction period, whereas SR141716A dose-dependently attenuated heroin seeking that was provoked by a priming injection of heroin (0.25 mg/kg) and heroin seeking that was triggered by re-exposure to heroin paired stimuli. CONCLUSIONS: The results show that the reinforcing and motivational effects of heroin and heroin-paired stimuli are mediated, at least in part, by activation of cannabinoid CB1 receptors. Therefore, the present study provides a rationale for the use of cannabinoid antagonists in the treatment of opiate addiction