Observing birth and placentophagia affects placentophagia but not maternal behavior of virgin rats

To determine whether observing components of periparturitional behavior affects the manifestation of those behaviors in virgin rats, virgins selected for nonplacentophagia and for the absence of spontaneous maternal behavior toward pups were exposed to stimulus rats that were giving birth, eating placenta, or eating lab chow. During observations, subjects could either eat donor placenta or just see and smell it. The subjects were tested subsequently for placentophagia and for the rate of onset of pup-induced maternal behavior. The results indicated that: (1) access to placenta in the presence of other rats led to placentophagia; (2) when such placentophagia occurred in conjunction with exposure to other rats that were giving birth or eating donor placenta, the subjects became permanent placentophages (otherwise, the subjects reverted and did not eat on subsequent placentophagia tests); (3) none of the observation conditions, regardless of the availability of placenta during observation, affected the maternal sensitization latency. The results are discussed in terms of social facilitation, exposure learning, and desensitization to exteroceptive stimuli

The effect of pregnancy and stress on the onset of placentophagia in Long-Evans rats

Most virgin rats do not eat placenta when it is presented to them; virtually all parturient rats do. This study was designed to examine the role of the duration and termination of pregnancy on the induction of placentophagia. Time-bred rats determined by a pretest not to be attracted to placenta (nonplacentophages), were tested for placentophagia on one of a number of days of pregnancy. A comparable group was tested for placentophagia after surgical termination of pregnancy on Day 21. Groups of virgins were run controlling for the time interval between the pretest and the placentophagia test, and for a time interval that included a "stressful" event. The results were that (a) the incidence of placentophagia rose gradually from Day 7 to Day 15 of pregnancy, then remained stable, at about 0.4 until delivery; (b) pregnancy termination did not produce an effect on placentophagia greater than that of unterminated pregnancy; (c) a pretest-test interval containing a "stressful" event produced significantly more placentophagia than one that did not contain such an event; and (d) the maximum level of placentophagia observed during pregnancy was the same as that produced in virgins by a "stressful" event

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

Peer reviewe

Neophobia and water intake after repeated pairings of novel flavors with toxicosis

The ability of rats (a) to acquire a generalized neophobia and (b) to maintain total daily fluid intake (by increasing intake of plain water) during the neophobia, was assessed. Rats trained to drink on a 23 1/2-hr water deprivation schedule were presented with a series of novel-flavored drinking solutions at 4-day intervals. Fifteen min of exposure to the novel flavor was followed first by 15 min of access to plain water, and then by an injection of lithium chloride. A saline-injected group and a noncontingent lithium chloride-injected group served as controls. Re-exposure to flavors did not occur between presentations of novel flavors. The rats in the group receiving novel flavors paired with toxicosis not only showed suppressed intake of all subsequent novel flavors after several pairings, but also eventually showed suppressed intake of plain water, which was limited to the days of novel-flavor presentation

Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Background: Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality. Methods: In this multicentre, prospective, parallel group, open label with blinded outcome assessment, randomised controlled trial, adult patients (aged ≥18 years) were included at 48 hospitals in Australia, Austria, Brazil, Canada, Finland, Ireland, New Zealand, Singapore, Spain, and the UK. Eligible patients with minor acute ischaemic stroke (National Institutes of Health Stroke Scale score 0–5) and intracranial occlusion or focal perfusion abnormality were enrolled within 12 h from stroke onset. Participants were randomly assigned (1:1), using a minimal sufficient balance algorithm to intravenous tenecteplase (0·25 mg/kg) or non-thrombolytic standard of care (control). Primary outcome was a return to baseline functioning on pre-morbid modified Rankin Scale score in the intention-to-treat (ITT) population (all patients randomly assigned to a treatment group and who did not withdraw consent to participate) assessed at 90 days. Safety outcomes were reported in the ITT population and included symptomatic intracranial haemorrhage and death. This trial is registered with ClinicalTrials.gov, NCT02398656, and is closed to accrual. Findings: The trial was stopped early for futility. Between April 27, 2015, and Jan 19, 2024, 886 patients were enrolled; 369 (42%) were female and 517 (58%) were male. 454 (51%) were assigned to control and 432 (49%) to intravenous tenecteplase. The primary outcome occurred in 338 (75%) of 452 patients in the control group and 309 (72%) of 432 in the tenecteplase group (risk ratio [RR] 0·96, 95% CI 0·88–1·04, p=0·29). More patients died in the tenecteplase group (20 deaths [5%]) than in the control group (five deaths [1%]; adjusted hazard ratio 3·8; 95% CI 1·4–10·2, p=0·0085). There were eight (2%) symptomatic intracranial haemorrhages in the tenecteplase group versus two (<1%) in the control group (RR 4·2; 95% CI 0·9–19·7, p=0·059). Interpretation: There was no benefit and possible harm from treatment with intravenous tenecteplase. Patients with minor stroke and intracranial occlusion should not be routinely treated with intravenous thrombolysis

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses