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Spatial discounting is a largely underexplored area of decision-making research, both theoretically and empirically, especially when compared to intertemporal choice, which has received significant attention in psychology and animal behaviour. SGX-523 mouse Spatial decision problems seem to share some of the same features of a temporal decision problem (namely, the risk of reward objects disappearing and the opportunity cost of waiting), but there are several additional factors that affect the appropriate discount function for distant rewards. These include more significant opportunity costs, changes in the distances to all the other available opportunities, the post-reward costs of getting back home, the complex energetics associated with locomotion and all the additional risks faced by travelling itself. This paper organises and explores these factors and suggests some normative models that should predict the adaptive behaviour of animals and humans.Thymol and carvacrol are phenolic isomers with the potential developmental toxicity and endocrine disruptions (ED) at low concentrations. However, few reports estimated their toxicity and ED below 10-6 M (150 μg/L) (MW of thymol and carvacrol 150 g/mol). In this study, both chemicals were determined for the developmental toxicity and potential ED at 500 μg/kg and 50 μg/kg using the chicken embryonic assay, potential estrogenic activity (EA) at 10-12 to 10-7 M (1.5 × 10-4 to 15 μg/L) by the MCF-7 cell proliferation assay, mutagenicity at 10-12 to 10-6 M (1.5 × 10-4 to 150 μg/L) by the Ames test, and an in silico method for ED. Carvacrol showed mutagenic risks at 10-7, 10-8, and 10-11 M (15, 1.5, and 0.0015 μg/L) while thymol at 10-6 and 10-8 M (150 and 1.5 μg/L). Carvacrol negatively impacted embryonic growth at 50 μg/kg, with weak EA at 10-8 M (1.5 μg/L). Carvacrol but not thymol had weak EA at 10-12 M (1.5 × 10-4 μg/L). Molecular docking to 14 types of hormone-related receptors revealed that carvacrol had higher binding affinities to two estrogen receptors and the mineralocorticoid receptor than those to thymol. Carvacrol and thymol varied in toxicities due to a different location of one phenolic hydroxyl group.The existing information supports the use of this material as described in this safety assessment. Cyclohexanol was evaluated for genotoxicity, repeated dose toxicity, reproductive toxicity, local respiratory toxicity, phototoxicity/photoallergenicity, skin sensitization, and environmental safety. Data show that cyclohexanol is not genotoxic. Data on cyclohexanol provide a calculated margin of exposure (MOE) >100 for the repeated dose toxicity and reproductive toxicity endpoints. Data show that there are no safety concerns for cyclohexanol for skin sensitization under the current declared levels of use. The phototoxicity/photoallergenicity endpoints were evaluated based on ultraviolet (UV) spectra; cyclohexanol is not expected to be phototoxic/photoallergenic. The local respiratory toxicity endpoint was evaluated using the threshold of toxicological concern (TTC) for a Cramer Class I material, and the exposure to cyclohexanol is below the TTC (1.4 mg/day). The environmental endpoints were evaluated; cyclohexanol was found not to be persistent, bioaccumulative, and toxic (PBT) as per the International Fragrance Association (IFRA) Environmental Standards, and its risk quotients, based on its current volume of use in Europe and North America (i.e., Predicted Environmental Concentration/Predicted No Effect Concentration [PEC/PNEC]), are less then 1.Methadone maintenance treatment (MMT) is the most common treatment for opioid-dependent pregnant women worldwide. Despite its widespread use, MMT is associated with a variety of adverse neurodevelopmental outcomes in exposed offspring, particularly cognitive impairments. The neurobiological abnormalities underlying these cognitive impairments are, however, poorly understood. This is, in part, due to a lack of animal models that represents the standard of care that methadone is administered in the clinic, with inconsistencies in the timing, doses and durations of treatment. Here we describe the characterisation of a clinically relevant rat model of MMT in which the long-term behavioural and neurobiological effects of prenatal methadone exposure can be assessed in adolescent offspring. Female Sprague-Dawley rats were treated orally with an ascending methadone dosage schedule (5, 10, 15, 20, 25 and 30 mg/kg/day), self-administered in drinking water prior to conception, throughout gestation and lactation. Pregnane GABAergic system.

Alcohol use disorder (AUD) shows a high prevalence and often takes a severe and chronic course. However, the underlying mechanisms still need to be better understood. There is increasing evidence for a role of sex hormones in AUD and for the importance of sex-separated concepts in addiction research. Nevertheless, only few data give insight into how progesterone is involved in AUD.

Serum progesterone levels were measured at baseline (during early abstinence) in 186 in-patients with AUD (19% premenopausal females, 20% postmenopausal females, 61% males) and at median 5days later. They were compared with those of 233 healthy control subjects (24% premenopausal females, 19% postmenopausal females, 57% males). We quantified craving with the Obsessive Compulsive Drinking Scale (OCDS) and visual analogue scales (VAS). Alcohol-related hospital readmissions within a 24-month period following initial in-patient treatment were recorded. We conducted analyses separately for sex and for menopausal status in female participants.

Postmenopausal females with AUD reported higher craving than premenopausal females. In postmenopausal females, higher baseline progesterone levels correlated with lower OCDS total craving and VAS craving, i.e., lower state craving and lower average, maximum, and less frequent craving during withdrawal. In males with AUD, progesterone levels at baseline tended to be higher than in controls and declined to follow-up. Alcohol-related readmissions were not significantly associated with serum progesterone levels.

We provide first evidence that progesterone levels correlate with craving in females with AUD.

We provide first evidence that progesterone levels correlate with craving in females with AUD.