Adolescence is the transitional period between childhood and adulthood, during which extensive brain development occurs. Since this period also overlaps with the initiation of drug use, it is ...important to consider how substance use during this time might produce long-term neurobiological alterations, especially against the backdrop of developmental changes in neurotransmission. Alcohol, cannabis, nicotine, and opioids all produce marked changes in the expression and function of the neurotransmitter and receptor systems with which they interact. These acute and chronic alterations also contribute to behavioral consequences ranging from increased addiction risk to cognitive or neuropsychiatric behavioral dysfunctions. The current review provides an in-depth overview and update of the developmental changes in neurotransmission during adolescence, as well as the impact of drug exposure during this neurodevelopmental window. While most of these factors have been studied in animal models, which are the focus of this review, future longitudinal studies in humans that assess neural function and behavior will help to confirm pre-clinical findings. Furthermore, the neural changes induced by each drug should also be considered in the context of other contributing factors, such as sex. Further understanding of these consequences can help in the identification of novel approaches for preventing and reversing the neurobiological effects of adolescent substance use.
Schizophrenia is a complex neuropsychiatric disorder with significant morbidity. Treatment options that address the spectrum of symptoms are limited, highlighting the need for innovative therapeutic ...approaches. Gamma Entrainment Using Sensory Stimulation (GENUS) is an emerging treatment for neuropsychiatric disorders that uses sensory stimulation to entrain impaired oscillatory network activity and restore brain function. Aberrant oscillatory activity often underlies the symptoms experienced by patients with schizophrenia. We propose that GENUS has therapeutic potential for schizophrenia. This paper reviews the current status of schizophrenia treatment and explores the use of sensory stimulation as an adjunctive treatment, specifically through gamma entrainment. Impaired gamma frequency entrainment is observed in patients, particularly in response to auditory and visual stimuli. Thus, sensory stimulation, such as music listening, may have therapeutic potential for individuals with schizophrenia. GENUS holds novel therapeutic potential to improve the lives of individuals with schizophrenia, but further research is required to determine the efficacy of GENUS, optimize its delivery and therapeutic window, and develop strategies for its implementation in specific patient populations.
•GENUS is a novel non-pharmacological therapeutic intervention.•This review examines if GENUS can be applied to schizophrenia.•Specific future research directions in clinical and preclinical models are proposed.
Patients with schizophrenia, and rodent models of the disease, both exhibit suppressed neurogenesis, with antipsychotics possibly enhancing neurogenesis in pre-clinical models. Nestin, a cytoskeletal ...protein, is implicated in neuronal differentiation and adult neurogenesis. We hypothesized that schizophrenia pathogenesis involves nestin downregulation; however, few studies have related nestin to schizophrenia. We assessed nestin protein concentration, prepulse inhibition (PPI), and social interaction in the MK-801 model of schizophrenia, with or without antipsychotic (clozapine) treatment. Adult male Sprague-Dawley rats were intraperitoneally administered saline or MK-801 (0.1 mg/kg) to produce a schizophrenia-like phenotype, with concomitant subcutaneous injections of vehicle or clozapine (5 mg/kg). PPI was assessed on days 1, 8, and 15, and social interaction was assessed on day 4. Hippocampus tissue samples were dissected for Western blotting of nestin concentration. MK-801 alone did not alter nestin concentration, while clozapine alone enhanced hippocampal nestin concentration; this effect was not apparent in animals with MK-801 and clozapine co-administration. MK-801 also produced schizophrenia-like PPI disruptions, some of which were reversed by clozapine. Social interaction deficits were not detected in this model. This is the first report of clozapine-induced enhancements of hippocampal nestin concentration that might be mediated by NMDA receptors. Future studies will explore the impact of neurodevelopmental nestin concentration on symptom onset and antipsychotic treatment.
Patients with a serious mental illness often use cannabis at higher rates than the general population and are also often diagnosed with cannabis use disorder. Clinical studies reveal a strong ...association between the psychoactive effects of cannabis and the symptoms of serious mental illnesses. Although some studies purport that cannabis may treat mental illnesses, others have highlighted the negative consequences of use for patients with a mental illness and for otherwise healthy users. As epidemiological and clinical studies are unable to directly infer causality or examine neurobiology through circuit manipulation, preclinical animal models remain a valuable resource for examining the causal effects of cannabis. This is especially true considering the diversity of constituents in the cannabis plant contributing to its effects. In this mini-review, we provide an updated perspective on the preclinical evidence of shared neurobiological mechanisms underpinning the dual diagnosis of cannabis use disorder and a serious mental illness. We present studies of cannabinoid exposure in otherwise healthy rodents, as well as rodent models of schizophrenia, depression, and bipolar disorder, and the resulting impact on electrophysiological indices of neural circuit activity. We propose a consolidated neural circuit-based understanding of the preclinical evidence to generate new hypotheses and identify novel therapeutic targets.
Abstract
Cannabis use is highly prevalent in patients with schizophrenia and worsens the course of the disorder. To understand how exposure to cannabis changes schizophrenia-related oscillatory ...disruptions, we investigated the impact of administering cannabis vapor containing either Δ9-tetrahydrocannabinol (THC) or balanced THC/cannabidiol (CBD) on oscillatory activity in the neonatal ventral hippocampal lesion (NVHL) rat model of schizophrenia. Male Sprague Dawley rats underwent lesion or sham surgeries on postnatal day 7. In adulthood, electrodes were implanted targeting the cingulate cortex (Cg), the prelimbic cortex (PrLC), the hippocampus (HIP), and the nucleus accumbens (NAc). Local field potential recordings were obtained after rats were administered either the “THC-only” cannabis vapor (8–18% THC/0% CBD) or the “Balanced THC:CBD” cannabis vapor (4–11% THC/8.5–15.5% CBD) in a cross-over design with a 2-week wash-out period between exposures. Compared to controls, NVHL rats had reduced baseline gamma power in the Cg, HIP, and NAc, and reduced HIP-Cg high-gamma coherence. THC-only vapor exposure broadly suppressed oscillatory power and coherence, even beyond the baseline reductions observed in NHVL rats. Balanced THC:CBD vapor, however, did not suppress oscillatory power and coherence, and in some instances enhanced power. For NVHL rats, THC-only vapor normalized the baseline HIP-Cg high-gamma coherence deficits. NHVL rats demonstrated a 20 ms delay in HIP theta to high-gamma phase coupling, which was not apparent in the PrLC and NAc after both exposures. In conclusion, cannabis vapor exposure has varying impacts on oscillatory activity in NVHL rats, and the relative composition of naturally occurring cannabinoids may contribute to this variability.
The endocannabinoid system is responsible for regulating a spectrum of physiological activities and plays a critical role in the developing brain. During adolescence, the endocannabinoid system is ...particularly sensitive to external insults that may change the brain’s developmental trajectory. Cannabinoid receptor type 2 (CB2R) was initially thought to predominantly function in the peripheral nervous system, but more recent studies have implicated its role in the mesolimbic pathway, a network largely attributed to reward circuitry and reward motivated behavior, which undergoes extensive changes during adolescence. It is therefore important to understand how CB2R modulation during adolescence can impact reward-related behaviors in adulthood. In this study, adolescent male rats (postnatal days 28–41) were exposed to a low or high dose of the CB2R antagonist/inverse agonist SR144528 and Pavlovian autoshaping and instrumental conditional behavioral outcomes were measured in adulthood. SR144528-treated rats had significantly slower acquisition of the autoshaping task, seen by less lever pressing behavior over time
F
(2, 19)
= 5.964,
p
= 0.010. Conversely, there was no effect of adolescent SR144528 exposure on instrumental conditioning. These results suggest that modulation of the CB2R in adolescence differentially impacts reward-learning behaviors in adulthood.
The Coma cluster, Abell 1656, was the target of an HST-ACS Treasury program designed for deep imaging in the F475W and F814W passbands. Although our survey was interrupted by the ACS instrument ...failure in early 2007, the partially completed survey still covers ~50% of the core high-density region in Coma. Observations were performed for 25 fields that extend over a wide range of cluster-centric radii (~1.75 Mpc or 1?) with a total coverage area of 274 arcmin2. The majority of the fields are located near the core region of Coma (19/25 pointings) with six additional fields in the southwest region of the cluster. In this paper, we present reprocessed images and SEXTRACTOR source catalogs for our survey fields, including a detailed description of the methodology used for object detection and photometry, the subtraction of bright galaxies to measure faint underlying objects, and the use of simulations to assess the photometric accuracy and completeness of our catalogs. We also use simulations to perform aperture corrections for the SEXTRACTOR Kron magnitudes based only on the measured source flux and its half-light radius. We have performed photometry for ~73,000 unique objects; approximately one-half of our detections are brighter than the 10 Delta *s point-source detection limit at F814W = 25.8 mag (AB). The slight majority of objects (60%) are unresolved or only marginally resolved by ACS. We estimate that Coma members are 5%-10% of all source detections, which consist of a large population of unresolved compact sources (primarily globular clusters but also ultra-compact dwarf galaxies) and a wide variety of extended galaxies from a cD galaxy to dwarf low surface brightness galaxies. The red sequence of Coma member galaxies has a color-magnitude relation with a constant slope and dispersion over 9 mag (--21 < M F814W < --13). The initial data release for the HST-ACS Coma Treasury program was made available to the public in 2008 August. The images and catalogs described in this study relate to our second data release.
A 19-year-old man received a gunshot wound to the heart. Transthoracic echocardiography was unable to localize the bullet fragment, whereas transesophageal echocardiography localized the bullet ...fragment in the posteroseptal wall at the base of the posteromedial papillary muscle.
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