Pavlovian Conditioning Between Cocaine Stimulant Effects and a Discrete Sensory Cue: Implementation of an Alternating Conditioning Procedure

Cocaine addiction is associated with an extremely high rate of relapse, the resumption of drug taking behavior following a period of abstinence. Relapse may be induced by exposure to drug-associated cues, stress, or drug challenge. Rodent models of addiction investigate reinstatement, the resumption of drug-seeking behavior following a period of abstinence. This study investigated the necessary procedures for establishing Pavlovian conditioning between a discrete sensory cue and cocaine stimulant effects (15.0 mg/kg, IP). Successful conditioning was indicated by cue induced conditioned hyperactivity. In Experiment 1, a simple discrete visual cue failed to be attributed salience. Cocaine-treated rats showed heightened locomotor activity independent of cue condition, suggestive of contextual conditioning. Experiment 2 replaced the simple visual cue with a compound auditory/visual cue and implemented various procedural adaptations to prevent contextual conditioning; comparable results were observed. Experiment 3 introduced an alternating cue conditioning/no cue conditioning training regimen with 6 drug-cue pairings over 12 days. This alternating training procedure minimized contextual conditioning and resulted in successful attribution of salience to the discrete cue for tests after 3, 14, and 28 days of withdrawal. This study suggests that an alternating drug-cue pairing training procedure can be used to establish conditioned locomotor activity specific to a discrete compound sensory cue in Sprague-Dawley rats

Pavlovian Conditioning Between Cocaine Stimulant Effects and a Discrete Sensory Cue: Implementation of an Alternating Conditioning Procedure

Cocaine addiction is associated with an extremely high rate of relapse, the resumption of drug taking behavior following a period of abstinence. Relapse may be induced by exposure to drug-associated cues, stress, or drug challenge. Rodent models of addiction investigate reinstatement, the resumption of drug-seeking behavior following a period of abstinence. This study investigated the necessary procedures for establishing Pavlovian conditioning between a discrete sensory cue and cocaine stimulant effects (15.0 mg/kg, IP). Successful conditioning was indicated by cue induced conditioned hyperactivity. In Experiment 1, a simple discrete visual cue failed to be attributed salience. Cocaine-treated rats showed heightened locomotor activity independent of cue condition, suggestive of contextual conditioning. Experiment 2 replaced the simple visual cue with a compound auditory/visual cue and implemented various procedural adaptations to prevent contextual conditioning; comparable results were observed. Experiment 3 introduced an alternating cue conditioning/no cue conditioning training regimen with 6 drug-cue pairings over 12 days. This alternating training procedure minimized contextual conditioning and resulted in successful attribution of salience to the discrete cue for tests after 3, 14, and 28 days of withdrawal. This study suggests that an alternating drug-cue pairing training procedure can be used to establish conditioned locomotor activity specific to a discrete compound sensory cue in Sprague-Dawley rats

Optical Apparatus and Method of Forming a Gradient Index Device

A refractive index device and method of making it include obtaining a glass structure comprising a plurality of nucleation sites. The glass structure is formed from a glass composition that comprises a first chemical component and a second chemical component. A crystal of the second chemical component has a different second refractive index from a first refractive index of the first chemical component. Each nucleation site defines where a crystal of the second chemical component can be grown. The method includes causing crystals of the second chemical component to grow in situ at a set of the plurality of nucleation sites in order to produce a spatial gradient of a refractive index in the glass structure

Cue-induced conditioned activity does not incubate but is mediated by the basolateral amygdala

Re-exposure to drug-associated cues causes significant drug craving in recovering addicts, which may precipitate relapse. In animal models of craving, drug-seeking responses for contingent delivery of drug-associated cues sensitizes or “incubates” across drug withdrawal. To date there is limited evidence supporting an incubation effect for behaviors mediated by non-contingent presentation of drug-associated cues. Here we used a model of cue-induced conditioned activity to determine if the conditioned locomotor response to a non-contingent presentation of a drug-associated cue sensitizes across drug withdrawal. In addition, because cue-induced drug-seeking responses are mediated by the rostral basolateral amygdala (BLA), we investigated whether this structure is critical for the expression of cue-induced conditioned activity. A conditioned association between cocaine (15 mg/kg) and a compound discrete cue (flashing bicycle light + a metronome) was established over 12 conditioning sessions in male Sprague–Dawley rats. In experiment 1, cue-induced conditioned activity was assessed on 3 occasions: 3, 14 and 28 days following the final drug–cue conditioning session. Cocaine-conditioned rats demonstrated reliable cue-induced conditioned activity across all 3 test sessions, however there was no evidence of an incubation effect. To determine whether repeated testing prevented the observation of an incubation effect, rats in experiment 2 were tested either 3 days or 28 days following conditioning; again no incubation effect was observed. In experiment 3, either saline or the GABAA receptor agonist muscimol was infused prior to testing. Intra-BLA infusions of muscimol prevented the expression of cue-induced conditioned activity. These data support the role of the rBLA in mediating conditioned responses to drug-associated cues. The failure to observe an incubation effect for cue-induced conditioned activity may point to a fundamental difference in the manner by which contingent and non-contingent presentations of drug-associated cues influence behavior

Evidence-based consensus guidelines for the management of catatonia: Recommendations from the British Association for Psychopharmacology

The British Association for Psychopharmacology developed an evidence-based consensus guideline on the management of catatonia. A group of international experts from a wide range of disciplines was assembled. Evidence was gathered from existing systematic reviews and the primary literature. Recommendations were made on the basis of this evidence and were graded in terms of their strength. The guideline initially covers the diagnosis, aetiology, clinical features and descriptive epidemiology of catatonia. Clinical assessments, including history, physical examination and investigations are then considered. Treatment with benzodiazepines, electroconvulsive therapy and other pharmacological and neuromodulatory therapies is covered. Special regard is given to periodic catatonia, malignant catatonia, neuroleptic malignant syndrome and antipsychotic-induced catatonia. There is attention to the needs of particular groups, namely children and adolescents, older adults, women in the perinatal period, people with autism spectrum disorder and those with certain medical conditions. Clinical trials were uncommon, and the recommendations in this guideline are mainly informed by small observational studies, case series and case reports, which highlights the need for randomised controlled trials and prospective cohort studies in this area

Mechanisms of Hearing Loss after Blast Injury to the Ear

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the bodyﾒs most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction

Global Retinoblastoma Presentation and Analysis by National Income Level.

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4%) were female. Most patients (n = 3685 [84.7%]) were from low- and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 [62.8%]), followed by strabismus (n = 429 [10.2%]) and proptosis (n = 309 [7.4%]). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 [95% CI, 12.94-24.80], and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 [95% CI, 4.30-7.68]). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs