The CB1 receptor antagonist AM251 impairs reconsolidation of pavlovian fear memory in the rat basolateral amygdala

We have investigated the requirement for signaling at CB1 receptors in the reconsolidation of a previously consolidated auditory fear memory, by infusing the CB1 receptor antagonist AM251, or the FAAH inhibitor URB597, directly into the basolateral amygdala (BLA) in conjunction with memory reactivation. AM251 disrupted memory restabilization, but only when administered after reactivation. URB597 produced a small, transient enhancement of memory restabilization when administered after reactivation. The amnestic effect of AM251 was rescued by coadministration of the GABAA receptor antagonist bicuculline at reactivation, indicating that the disruption of reconsolidation was mediated by altered GABAergic transmission in the BLA. These data show that the endocannabinoid system in the BLA is an important modulator of fear memory reconsolidation and that its effects on memory are mediated by an interaction with the GABAergic system. Thus, targeting the endocannabinoid system may have therapeutic potential to reduce the impact of maladaptive memories in neuropsychiatric disorders such as posttraumatic stress disorder.This work was conducted within the Behavioural and Clinical Neuroscience Institute, a joint initiative funded by the Wellcome Trust and the UK Medical Research Council, in the Department of Psychology at the University of Cambridge. This work was funded by a UK Medical Research Council programme grant (no. G1002231) awarded to BJE and ALM. PR was supported by a Department of Physiology and Pharmacology Fellowship at the Sapienza University of Rome, and an Italian Society of Pharmacology Fellowship. ALM is the Ferreras-Willetts Fellow in Neuroscience at Downing College, Cambridge. The manuscript was partly prepared while ALM was an Erskine Visiting Cambridge Fellow at the University of Canterbury, Christchurch, New Zealand

Developmental consequences of perinatal cannabis exposure: behavioral and neuroendocrine effects in adult rodents

Cannabis is the most commonly used illicit drug among pregnant women. Since the endocannabinoid system plays a crucial role in brain development, maternal exposure to cannabis derivatives might result in long-lasting neurobehavioral abnormalities in the exposed offspring. It is difficult to detect these effects, and their underlying neurobiological mechanisms, in clinical cohorts, because of their intrinsic methodological and interpretative issues. The present paper reviews relevant rodent studies examining the long-term behavioral consequences of exposure to cannabinoid compounds during pregnancy and/or lactation. Maternal exposure to even low doses of cannabinoid compounds results in atypical locomotor activity, cognitive impairments, altered emotional behavior, and enhanced sensitivity to drugs of abuse in the adult rodent offspring. Some of the observed behavioral abnormalities might be related to alterations in stress hormone levels induced by maternal cannabis exposure. There is increasing evidence from animal studies showing that cannabinoid drugs are neuroteratogens which induce enduring neurobehavioral abnormalities in the exposed offspring. Several preclinical findings reviewed in this paper are in line with clinical studies reporting hyperactivity, cognitive impairments and altered emotionality in humans exposed in utero to cannabis. Conversely, genetic, environmental and social factors could also influence the neurobiological effects of early cannabis exposure in humans

Cement augmentation for trochanteric fracture in elderly: A systematic review

Background: Cement augmentation of internal fixation of hip fracture has reported to improve fracture stability in osteoporotic hip fractures, reducing the risk of cut-out of the sliding screw through the femoral head. The purpose of present study was to perform a systematic literature review on the effects of augmentation technique in patients with osteoporotic hip fractures. Material and methods: A comprehensive literature search was systematically performed to evaluate all papers published in English language included in the literature between January 2010 and July 2020, according to the PRISMA 2009 guidelines. In vivo and in vitro studies, case reports, review articles, cadaveric studies, biomechanical studies, histological studies, oncological studies, technical notes, studies dealing with radiological classifications and studies on revision surgery were excluded. Results: A total of 5 studies involving 301 patients were included. Patients had a mean age of 84.6 years and were followed up for a mean period of 11 months. The proximal femoral fractures were stabilized with implantation of the PFNA or Gamma nail and augmentation was performed with two different cements: polymethylmethacrylate (PMMA) in 4 studies and calcium phosphate (CP) in one study. Overall, 57.5% of patients reached the same or greater preoperative mobility, and postoperative Parker Mobility Score and Harris Hip Score were acceptable. No significantly complications were observed, and no additional surgery related to the implant was required. Conclusion: The results of this systematic review show that cement augmentation is a safe and effectiveness method of fixation to treat trochanteric fractures