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Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Recent Research Articles from UNTHSC - Tue, 10/27/2015 - 07:29
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Total cholesterol and neuropsychiatric symptoms in Alzheimer's disease: the impact of total cholesterol level and gender.

Dement Geriatr Cogn Disord. 2014;38(5-6):300-9

Authors: Hall JR, Wiechmann AR, Johnson LA, Edwards M, Barber RC, Cunningham R, Singh M, O'Bryant SE

Abstract
BACKGROUND: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are a major factor in nursing home placement and a primary cause of stress for caregivers. Elevated cholesterol has been linked to psychiatric disorders and has been shown to be a risk factor for AD and to impact disease progression. The present study investigated the relationship between cholesterol and NPS in AD.
METHODS: Data on cholesterol and NPS from 220 individuals (144 females, 76 males) with mild-to-moderate AD from the Texas Alzheimer's Research and Care Consortium (TARCC) cohort were analyzed. The total number of NPS and symptoms of hyperactivity, psychosis, affect and apathy were evaluated. Groups based on total cholesterol (TC; ≥200 vs. <200 mg/dl) were compared with regard to NPS. The impact of gender was also assessed.
RESULTS: Individuals with high TC had lower MMSE scores as well as significantly more NPS and more symptoms of psychosis. When stratified by gender, males with high TC had significantly more NPS than females with high TC or than males or females with low TC.
CONCLUSION: The role of elevated cholesterol in the occurrence of NPS in AD appears to be gender and symptom specific. A cross-validation of these findings will have implications for possible treatment interventions, especially for males with high TC.

PMID: 25011444 [PubMed - indexed for MEDLINE]

The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Recent Research Articles from UNTHSC - Sat, 10/24/2015 - 07:33
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The cross-sectional association between severity of non-cognitive disability and self-reported worsening memory.

Disabil Health J. 2015 Sep 25;

Authors: Cannell MB, Bouldin ED, Teigen K, Akhtar WZ, Andresen EM

Abstract
BACKGROUND: Research has demonstrated a clear association between cognitive decline and non-cognitive disability; however, all of these studies focus on disability as a correlate or result of some level of cognitive impairment or dysfunction. The relationship between disability and cognition is likely a complex one, that is currently incompletely described in the literature.
OBJECTIVES: Our objective was to estimate the prevalence of long-term, non-cognitive disability using a population-representative sample of adults aged 18 and older, and then estimate the association between long-term, non-cognitive disability and self-reported worsening memory.
METHODS: Using the 2009 Florida Behavioral Risk Factor Surveillance System (BRFSS), we measured the relationship between non-cognitive disability and worsening memory using multivariable logistic regression analysis weighted to account for the complex sampling design of the BRFSS. We also estimated the adjusted odds of worsening memory by disability severity, classified according to the types of assistance needed.
RESULTS: Approximately 18% (95% confidence interval = (16%, 19%)) of Floridians were living with a long-term, non-cognitive disability in 2009. Among adults with no disability during or prior to the last year, only 5% reported worsening memory. The proportion of Floridians reporting worsening memory increases with increasing severity of disability-related limitations. In a multivariable logistic regression model, odds of worsening memory increased significantly with severity of disability-related limitations.
CONCLUSIONS: These results highlight the association between non-cognitive disability and subsequent increased odds of worsening memory, independent of several other known risk factors, and a dose-response association with disability-related limitations.

PMID: 26493638 [PubMed - as supplied by publisher]

Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

Recent Research Articles from UNTHSC - Sat, 10/24/2015 - 07:33
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Nicotine enhances inhibition of mouse vagal motor neurons by modulating excitability of premotor GABAergic neurons in the nucleus tractus solitarii.

J Neurophysiol. 2015 Feb 15;113(4):1165-74

Authors: Xu H, Boychuk JA, Boychuk CR, Uteshev VV, Smith BN

Abstract
The caudal nucleus of the solitary tract (NTS) serves as the site of the first synapse for visceral sensory inputs to the central nervous system. The NTS sends functional projections to multiple brain nuclei, with gastric-related projections primarily targeting the dorsal motor nucleus of the vagus (DMV). Previous studies have demonstrated that the majority of caudal NTS neurons that project to the DMV respond robustly to nicotine and express nicotinic acetylcholine receptors (nAChRs). However, the cytochemical identity and relationship with specific viscera of DMV-projecting, nicotine-responsive caudal NTS neurons have not been determined. The present study used transgenic mice that express enhanced green fluorescent protein (EGFP) under a GAD67 promoter in a subset of GABAergic neurons, in vivo retrograde pseudorabies viral labeling to identify gastric-related vagal complex neurons, and patch-clamp electrophysiology in acute brain stem slices to test the hypothesis that gastric-related and GABAergic inhibitory synaptic input to the DMV from the caudal NTS is under a robust modulatory control by nAChRs. Our results suggest that activation of nAChRs in the caudal NTS, but not DMV, potentiates GABAergic, but not glutamatergic, input to the DMV. Gastric-related caudal NTS and DMV neurons are directly involved in this nicotine-sensitive circuitry. Understanding the central patterns of nicotinic modulation of visceral sensory-motor circuitry may help develop therapeutic interventions to restore autonomic homeostasis in patients with autonomic impairments.

PMID: 25429117 [PubMed - indexed for MEDLINE]

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Recent Research Articles from UNTHSC - Fri, 10/23/2015 - 07:29

Y BALANCE TEST™ ANTERIOR REACH SYMMETRY AT THREE MONTHS IS RELATED TO SINGLE LEG FUNCTIONAL PERFORMANCE AT TIME OF RETURN TO SPORTS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION.

Int J Sports Phys Ther. 2015 Oct;10(5):602-11

Authors: Garrison JC, Bothwell JM, Wolf G, Aryal S, Thigpen CA

Abstract
BACKGROUND: Restoration of symmetrical strength, balance, and power following anterior cruciate ligament reconstruction (ACL-R) are thought to be important factors for successful return to sports. Little information is available regarding early rehabilitation outcomes and achieving suggested limb indices of 90% on functional performance measures at the time of return to sports (RTS).
HYPOTHESIS/PURPOSE: To examine the relationship between symmetry of the anterior reach of the Y Balance Test™ at 12 weeks and functional performance measures at time of return to sports after anterior cruciate ligament (ACL) reconstruction.
STUDY DESIGN: Retrospective Cohort.
METHODS: Forty subjects (mean ± SD age, 17.2 ± 3.8 years) who were in the process of rehabilitation following ACL reconstruction. Each subject volunteered and was enrolled in the study during physical therapy following ACL-R. Participants averaged two visits per week in physical therapy until the time of testing for RTS. The Y Balance Test™ was assessed at 12 weeks. Participants completed a battery of tests at RTS (6.4 ± 1.1 months) including triple hop distance (THD), single hop distance (SHD), isometric knee extension strength (KE), and the Vail Sport Test™. Side to side difference was calculated for the Y Balance Test™ anterior reach and limb symmetry indices (LSI) were computed for THD, SHD, and KE. Multiple regression models were used to study the relationship between variables at 12 weeks and RTS while controlling for age, gender, type of graft, and pain score. In addition, subjects were dichotomized based on a side-to-side Y Balance anterior reach difference into high risk (>4 cm) or low risk (≤4 cm) categories. A receiver operating characteristic (ROC) curve was used to identify individuals at 12 weeks who do not achieve 90% limb symmetry indices at time of RTS testing. .
RESULTS: A statistically significant association was seen between Y Balance ANT at 12 weeks and SHD at RTS (β = -1.46, p = 0.0005, R(2) = 0.395), THD at RTS (β = -1.08, p = 0.0011, R(2) = 0.354) and KE at RTS (β = -1.00, p = 0.0025, R(2) = 0.279) after adjusting for age, gender, type of graft and pain score at week 12. There was no significant association between Y Balance ANT at 12 weeks and Vail Sport Test at RTS (p = 0.273). ROC curves indicated that the Y Balance ANT at 12 weeks identified participants who did not achieve 90% LSI for the SHD (AUC = 0.82 p = 0.02) and THD (AUC=0.85, p = 0.01) at RTS with a sensitivity of 0.96 (SHD) and 0.92 (THD) respectively.
CONCLUSIONS: Participants following ACL-R who demonstrated > 4 cm Y Balance ANT deficits at 12 weeks on their involved limb did not tend to achieve 90% LSI for the SHD and THD at time of return to sports. The Y Balance ANT at 12 weeks and Vail Sport Test™ appear to measure different constructs following ACL-R.
LEVELS OF EVIDENCE: Level 3.

PMID: 26491610 [PubMed]

The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

Recent Research Articles from UNTHSC - Tue, 10/20/2015 - 07:29
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The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations.

J Prev Alzheimers Dis. 2014 Dec;1(3):181-202

Authors: Cavedo E, Lista S, Khachaturian Z, Aisen P, Amouyel P, Herholz K, Jack CR, Sperling R, Cummings J, Blennow K, O'Bryant S, Frisoni GB, Khachaturian A, Kivipelto M, Klunk W, Broich K, Andrieu S, de Schotten MT, Mangin JF, Lammertsma AA, Johnson K, Teipel S, Drzezga A, Bokde A, Colliot O, Bakardjian H, Zetterberg H, Dubois B, Vellas B, Schneider LS, Hampel H

Abstract
Alzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in which pathophysiological abnormalities, detectable in vivo by biological markers, precede overt clinical symptoms by many years to decades. Use of these biomarkers for the detection of early and preclinical AD has become of central importance following publication of two international expert working group's revised criteria for the diagnosis of AD dementia, mild cognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequence of matured research evidence six AD biomarkers are sufficiently validated and partly qualified to be incorporated into operationalized clinical diagnostic criteria and use in primary and secondary prevention trials. These biomarkers fall into two molecular categories: biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-protein related hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("core feasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF) analytes. CSF Aβ1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 & Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI and AD dementia. Conversely, having all three biomarkers in the normal range rules out AD. Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI) at increasing field strength and resolution allows detecting the evolution of distinct types of structural and functional abnormality pattern throughout early to late AD stages. Anatomical or volumetric MRI is the most widely used technique and provides local and global measures of atrophy. The revised diagnostic criteria for "prodromal AD" and "mild cognitive impairment due to AD" include hippocampal atrophy (as the fourth validated biomarker), which is considered an indicator of regional neuronal injury. Advanced image analysis techniques generate automatic and reproducible measures both in regions of interest, such as the hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) and advanced tractography as well as resting-state functional MRI provide useful additionally useful measures indicating the degree of fiber tract and neural network disintegration (structural, effective and functional connectivity) that may substantially contribute to early detection and the mapping of progression. These modalities require further standardization and validation. The use of molecular in vivo amyloid imaging agents (the fifth validated biomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such as fluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection of early AD pathological processes and associated neurodegeneration. How to use, interpret, and disclose biomarker results drives the need for optimized standardization. Multimodal AD biomarkers do not evolve in an identical manner but rather in a sequential but temporally overlapping fashion. Models of the temporal evolution of AD biomarkers can take the form of plots of biomarker severity (degree of abnormality) versus time. AD biomarkers can be combined to increase accuracy or risk. A list of genetic risk factors is increasingly included in secondary prevention trials to stratify and select individuals at genetic risk of AD. Although most of these biomarker candidates are not yet qualified and approved by regulatory authorities for their intended use in drug trials, they are nonetheless applied in ongoing clinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patient stratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety. Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic, electrophysiological, and neuroimaging markers for use in clinical trials are being developed. The current state-of-the-art and future perspectives on both biological and neuroimaging derived biomarker discovery and development as well as the intended application in prevention trials is outlined in the present publication.

PMID: 26478889 [PubMed - as supplied by publisher]

Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

Recent Research Articles from UNTHSC - Tue, 10/20/2015 - 07:29
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Effect of Posterior Tibial Slope on Flexion and Anterior-Posterior Tibial Translation in Posterior Cruciate-Retaining Total Knee Arthroplasty.

J Arthroplasty. 2015 Aug 29;

Authors: Chambers AW, Wood AR, Kosmopoulos V, Sanchez HB, Wagner RA

Abstract
Reduced posterior tibial slope (PTS) and posterior tibiofemoral translation (PTFT) in posterior cruciate-retaining (PCR) total knee arthroplasty (TKA) may result in suboptimal flexion. We evaluated the relationship between PTS, PTFT, and total knee flexion after PCR TKA in a cadaveric model. We performed a balanced PCR TKA using 9 transfemoral cadaver specimens and changed postoperative PTS in 1° increments. We measured maximal flexion and relative PTFT at maximal flexion. We determined significant changes in flexion and PTFT as a function of PTS. Findings showed an average increase in flexion of 2.3° and average PTFT increase of 1mm per degree of PTS increase when increasing PTS from 1° to 4° (P<.05). Small initial increases in PTS appear to significantly increase knee flexion and PTFT.

PMID: 26476469 [PubMed - as supplied by publisher]

The structural basis of an NADP⁺-independent dithiol oxidase in FK228 biosynthesis.

Recent Research Articles from UNTHSC - Tue, 10/20/2015 - 07:29
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The structural basis of an NADP⁺-independent dithiol oxidase in FK228 biosynthesis.

Sci Rep. 2014;4:4145

Authors: Li J, Wang C, Zhang ZM, Cheng YQ, Zhou J

Abstract
The disulfide bond is unusual in natural products and critical for thermal stability, cell permeability and bioactivity. DepH from Chromobacterium violaceum No. 968 is an FAD-dependent enzyme responsible for catalyzing the disulfide bond formation of FK228, an anticancer prodrug approved for the treatment of cutaneous T-cell lymphoma. Here we report the crystal structures of DepH and DepH complexed with a substrate analogue S,S'-dimethyl FK228 at 1.82 Å and 2.00 Å, respectively. Structural and biochemical analyses revealed that DepH, in contrast to the well characterized low molecular weight thioredoxin reductases (LMW TrxRs), is an NADP(+)-independent dithiol oxidase. DepH not only lacks a conserved GGGDXAXE motif necessary for NADP(+) binding in the canonical LMW TrxRs, but also contains a 11-residue sequence which physically impedes the binding of NADP(+). These observations explain the difference between NADP(+)-independent small molecule dithiol oxidases and NADP(+)-dependent thioredoxin reductases and provide insights for understanding the catalytic mechanism of dithiol oxidases involved in natural product biosynthesis.

PMID: 24553401 [PubMed - indexed for MEDLINE]

Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

Recent Research Articles from UNTHSC - Sat, 10/17/2015 - 07:32
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Curcumin Mimics the Neurocognitive and Anti-Inflammatory Effects of Caloric Restriction in a Mouse Model of Midlife Obesity.

PLoS One. 2015;10(10):e0140431

Authors: Sarker MR, Franks S, Sumien N, Thangthaeng N, Filipetto F, Forster M

Abstract
Dietary curcumin was studied for its potential to decrease adiposity and reverse obesity- associated cognitive impairment in a mouse model of midlife sedentary obesity. We hypothesized that curcumin intake, by decreasing adiposity, would improve cognitive function in a manner comparable to caloric restriction (CR), a weight loss regimen. 15-month-old male C57BL/6 mice were assigned in groups to receive the following dietary regimens for 12 weeks: (i) a base diet (Ain93M) fed ad libitum (AL), (ii) the base diet restricted to 70% of ad libitum (CR) or (iii) the base diet containing curcumin fed AL (1000 mg/kg diet, CURAL). Blood markers of inflammation, interleukin 6 (IL-6) and C-reactive protein (CRP), as well as an indicator of redox stress (GSH: GSSG ratio), were determined at different time points during the treatments, and visceral and subcutaneous adipose tissue were measured upon completion of the experiment. After 8 weeks of dietary treatment, the mice were tested for spatial cognition (Morris water maze) and cognitive flexibility (discriminated active avoidance). The CR group showed significant weight loss and reduced adiposity, whereas CURAL mice had stable weight throughout the experiment, consumed more food than the AL group, with no reduction of adiposity. However, both CR and CURAL groups took fewer trials than AL to reach criterion during the reversal sessions of the active avoidance task, suggesting an improvement in cognitive flexibility. The AL mice had higher levels of CRP compared to CURAL and CR, and GSH as well as the GSH: GSSG ratio were increased during curcumin intake, suggesting a reducing shift in the redox state. The results suggest that, independent of their effects on adiposity; dietary curcumin and caloric restriction have positive effects on frontal cortical functions that could be linked to anti-inflammatory or antioxidant actions.

PMID: 26473740 [PubMed - as supplied by publisher]

Epidemiological and clinical profiles of respiratory syncytial virus infection in hospitalized neonates in Suzhou, China.

Recent Research Articles from UNTHSC - Sat, 10/17/2015 - 07:32
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Epidemiological and clinical profiles of respiratory syncytial virus infection in hospitalized neonates in Suzhou, China.

BMC Infect Dis. 2015;15(1):431

Authors: Lu L, Yan Y, Yang B, Xiao Z, Feng X, Wang Y, Ji W, Mize M, Hao C, Chen Z

Abstract
BACKGROUND: This study was designed to explore the epidemiological and clinical profiles of respiratory syncytial virus (RSV) infection in neonates from the Suzhou area of China, taking into consideration how climate factors influence disease.
METHODS: From 2010 to 2014, nasopharyngeal aspirates (NPA) collected from hospitalized neonates with lower respiratory tract infections (LRIs) were screened for seven common respiratory viruses including RSV by direct immunofluorescence assay. Human bocavirus, human metapneumovirus, and mycoplasma pneumoniae were detected by polymerase chain reaction.
RESULTS: Of the 1803 hospitalized neonates analyzed, 20.74 % were found to be infected with RSV. Interestingly, 30 subjects were identified as being coinfected with other viruses. The rate of RSV infection was highestduring thewinter and early spring seasons; however, infection was negatively associated with monthly mean temperature (rs = -0.821, P < 0.0001), total rainfall (rs = -0.406, P = 0.002), and sum of sunshine (rs = -0.386, P = 0.001). Monthly mean temperature was the only independent factor associated with RSV activity, as determined using multivariate regression analysis. Compared with non-RSV neonates, neonates with RSV infection presented more frequently with tachypnea,moist rales, and abnormal chest X-rays requiring supplemental oxygen and extended hospitalization postpartum. Neonatal admittance into the NICU was determined based on prematurity and coinfection with other viruses; two independent risk factors for RSV disease, as determined by multivariate logistic analysis.
CONCLUSIONS: Important as a major cause of LRIs in hospitalized neonate, we found that the subtropical climate of the Suzhou area was associated with RSV activity. The identified risk factors ofsevere disease in neonates with RSV infection should be taken into consideration when implementing disease health interventions.

PMID: 26470889 [PubMed - in process]

Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex.

Recent Research Articles from UNTHSC - Sat, 10/17/2015 - 07:32
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Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex.

Am J Physiol Heart Circ Physiol. 2015 Aug 1;309(3):H381-92

Authors: Michelini LC, O'Leary DS, Raven PB, Nóbrega AC

Abstract
The last 100 years witnessed a rapid and progressive development of the body of knowledge concerning the neural control of the cardiovascular system in health and disease. The understanding of the complexity and the relevance of the neuroregulatory system continues to evolve and as a result raises new questions. The purpose of this review is to articulate results from studies involving experimental models in animals as well as in humans concerning the interaction between the neural mechanisms mediating the hemodynamic responses during exercise. The review describes the arterial baroreflex, the pivotal mechanism controlling mean arterial blood pressure and its fluctuations along with the two main activation mechanisms to exercise: central command (parallel activation of central somatomotor and autonomic descending pathways) and the muscle metaboreflex, the metabolic component of exercise pressor reflex (feedback from ergoreceptors within contracting skeletal muscles). In addition, the role of the cardiopulmonary baroreceptors in modulating the resetting of arterial baroreflex is identified, and the mechanisms in the central nervous system involved with the resetting of baroreflex function during dynamic exercise are also described. Approaching a very relevant clinical condition, the review also presents the concept that the impaired arterial baroreflex function is an integral component of the metaboreflex-mediated exaggerated sympathetic tone in subjects with heart failure. This increased sympathetic activity has a major role in causing the depressed ventricular function observed during submaximal dynamic exercise in these patients. The potential contribution of a metaboreflex arising from respiratory muscles is also considered.

PMID: 26024683 [PubMed - indexed for MEDLINE]

The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Recent Research Articles from UNTHSC - Sat, 10/17/2015 - 07:32
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The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.

Psychopharmacology (Berl). 2015 Jan;232(1):275-84

Authors: Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB

Abstract
RATIONALE: Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens.
OBJECTIVE: The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT).
METHODS: Drug discrimination, head twitch, and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084), and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT.
RESULTS: MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT's effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low-potency full agonist at 5-HT2CR in vitro.
CONCLUSIONS: The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.

PMID: 24985890 [PubMed - indexed for MEDLINE]

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