Abstract:
BACKGROUND:Atypical antipsychotic drugs, particularly olanzapine, represent a mainstay in the treatment of psychoses; however, their use is commonly associated with weight gain and diabetes. The aim of this study was to determine whether combined administration of olanzapine and zonisamide can be used to prevent olanzapine-induced metabolic disturbances. METHODS AND RESULTS:These experiments involved female Sprague Dawley rats (n = 6-8/group) that were administered olanzapine, either acutely (6 mg/kg, s. c) or via continuous osmotic minipump infusion (6 mg/kg/day for 6 or 14 days), in combination with zonisamide (26 mg/kg/day,i.p.). Continuous infusion of olanzapine induced accumulation of adipose tissue and an associated reduction in stimulated lipolysis and reduced protein expression of CGI-58, a critical co-activator of ATGL. Olanzapine treatment caused a preferential shift toward carbohydrate oxidation (or reduced fat oxidation), elevated blood triglycerides and a reduction in locomotor activity. Olanzapine had a direct effect on glucose regulation, causing rapid hyperglycemia, and a reduction in glucose tolerance and insulin sensitivity. Continuous administration of olanzapine caused significant hyperinsulinemia and a significant reduction in insulin sensitivity. Zonisamide did not affect the impact of olanzapine on glucose homeostasis. On the other hand, co-administration of olanzapine with zonisamide completely ameliorated olanzapine-mediated shifts in lipid metabolism resulting in a normalization of olanzapine-induced weight gain. CONCLUSION:These data collectively show an impact of olanzapine on body weight and lipid metabolism, which is ameliorated by co-administration with zonisamide. These findings suggest that a combined olanzapine and zonisamide approach might reduce weight gain, but will not provide protection against olanzapine-induced glucose intolerance.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Stefanidis A,Watt MJ,Cowley MA,Oldfield BJdoi
10.1016/j.neuropharm.2017.04.010subject
Has Abstractpub_date
2017-09-01 00:00:00pages
55-66eissn
0028-3908issn
1873-7064pii
S0028-3908(17)30151-Xjournal_volume
123pub_type
杂志文章abstract::gamma-Aminobutyric acid type A (GABA(A)) receptors are an important target for general anesthetics in the central nervous system. Site-directed mutagenesis techniques have identified amino acid residues that are important for the positive modulation of GABA(A) receptors by general anesthetics. In the present study, we...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00141-1
更新日期:2001-12-01 00:00:00
abstract::The in vitro and in vivo properties of L-655,708, a compound with higher affinity for GABA(A) receptors containing an alpha5 compared to an alpha1, alpha2 or alpha3 subunit have been examined further. This compound has weak partial inverse agonist efficacy at each of the four subtypes but, and consistent with the bind...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.04.018
更新日期:2006-11-01 00:00:00
abstract::Several studies on humans and mice support oxytocin's role in improving social behaviour, but its use in pharmacotherapy presents some important limiting factors. To date, it is emerging a pharmacological potential for melanocortin 4 receptor (MC4R) agonism in social deficits treatment. Recently, we demonstrated that ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.02.007
更新日期:2018-05-01 00:00:00
abstract::The majority of existing research on the function of metabotropic glutamate (mGlu) receptor 1 focuses on G protein-mediated outcomes. However, similar to other G protein-coupled receptors (GPCR), it is becoming apparent that mGlu1 receptor signaling is multi-dimensional and does not always involve G protein activation...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.02.007
更新日期:2015-06-01 00:00:00
abstract::The effects of d- and l-amphetamine were studied on key-pressing responses of squirrel monkeys maintained under fixed-interval schedules of electric shock presentation, and on key-pecking responses of pigeons maintained under multiple fixed-ratio, fixed-interval schedules of food presentation. Under the fixed-interval...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(82)90193-9
更新日期:1982-03-01 00:00:00
abstract::Chronic activity perturbations in neurons induce homeostatic plasticity through modulation of synaptic strength or other intrinsic properties to maintain the correct physiological range of excitability. Although similar plasticity can also occur at the population level, what molecular mechanisms are involved remain un...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2018.06.011
更新日期:2018-08-01 00:00:00
abstract::Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. TSC is characterized by benign tumors arising in different organs and severe neuropsychiatric symp...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.11.003
更新日期:2013-04-01 00:00:00
abstract::An infusion of dopamine for 13 days into the nucleus accumbens of rat caused biphasic peaks of hyperactivity responding during infusion and an enhanced locomotor responsiveness to the dopamine agonist (-)N-n-propylnorapomorphine [(-)NPA] after the infusion when rats where initially preselected as low activity responde...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90073-5
更新日期:1985-03-01 00:00:00
abstract::The rat hemisected spinal cord preparation was used to assess the role of different adrenoceptor subtypes on the modulation of nociceptive reflexes. These were elicited by trains of high intensity electrical stimuli delivered to a lumbar dorsal root. Responses were recorded from the corresponding ventral root in AC- a...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00117-4
更新日期:2001-12-01 00:00:00
abstract::Mice deficient in the microtubule stabilizing protein STOP (stable tubule only polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper-reactivity in the limbic system and severe behavioral deficits. Some of these disturbances are alleviated by long-term antipsychotic treatment. Therefore, this m...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.03.015
更新日期:2007-06-01 00:00:00
abstract::Acetylcholine-induced currents were measured in partially depolarized mouse soleus muscles, denervated for 3-6 days by using a point voltage clamp. When 0.25 microM d-tubocurarine (d-Tc) was used, the weak currents provoked by 0.1 microM ACh, at a holding potential of -20 mV, were barely affected, while the large curr...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(90)90070-8
更新日期:1990-06-01 00:00:00
abstract::Administration of serotonin-enhancing drugs induces a distinctive behavioral syndrome in rodents. We previously reported that mice with a targeted disruption of the serotonin transporter (SERT) display some of these behaviors spontaneously, in the absence of drug. In the current studies, we assessed the drug-induced s...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.07.009
更新日期:2007-10-01 00:00:00
abstract::Alpha2-adrenergic drugs modulate cortical arousal and EEG. However, the role of individual alpha2-adrenoceptor (alpha(2)-AR) subtypes in these functions is not clear. We investigated the role of alpha(2C)-ARs in the modulation of baseline cortical EEG activity and EEG responses to the alpha(2)-AR selective agonist, de...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(02)00305-2
更新日期:2002-12-01 00:00:00
abstract::Vulnerability to the addictive effects of drugs of abuse varies among individuals, but the biological basis of these differences are poorly known. This work tries to increase this knowledge by comparing the brain proteome of animals with different rate of extinction of cocaine-seeking behaviour. To achieve this goal, ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.04.005
更新日期:2009-07-01 00:00:00
abstract::Quinine and quinidine are reported to potentiate the behavioural effects of serotonergic agents and monoamine uptake inhibitors. We have therefore investigated the presynaptic actions of quinine and quinidine on monoamine uptake and release in rat brain tissue in vitro. Quinidine evoked the release of [3H]5-HT, [3H]no...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(98)00075-6
更新日期:1998-07-01 00:00:00
abstract::Following injection of 5 micrograms of the competitive NMDA receptor antagonist AP-5 into the nucleus accumbens of monoamine-depleted mice a pronounced locomotor stimulation was produced. Additional treatment with an intraperitoneal (i.p.) injection of the alpha-adrenoceptor agonist clonidine markedly increased the lo...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(92)90092-4
更新日期:1992-05-01 00:00:00
abstract::Two peptide fragments of native Protein Kinase A inhibitor (PKI), PKI-(6-22)-amide and PKI-(Myr-14-22)-amide, significantly reversed low-level morphine antinociceptive tolerance in mice. The inhibition of Protein Kinase A (PKA) activity by both peptide fragments was then measured in specific brain regions (thalamus, p...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.12.006
更新日期:2005-04-01 00:00:00
abstract::Pyrantel is an anthelmintic which acts as an agonist of nicotinic receptors (AChRs) of nematodes and exerts its therapeutic effects by depolarizing their muscle membranes. Here we explore at the single-channel level the action of pyrantel at mammalian muscle AChR. AChR currents are elicited by pyrantel. However, openi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(01)00057-0
更新日期:2001-08-01 00:00:00
abstract:BACKGROUND:Alcohol use disorder (AUD) develops after chronic and heavy use of alcohol. Insomnia, a hallmark of AUD, plays a crucial role in the development of AUD. However, the causal mechanisms are unknown. Since chronic alcohol reduces acetylated histones and disrupts the epigenome, we hypothesized that chronic alcoh...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.108332
更新日期:2020-12-01 00:00:00
abstract::Acute morphine administration produces analgesia and reward, but prolonged use may lead to analgesic tolerance in patients chronically treated for pain and to compulsive intake in opioid addicts. Moreover, long-term exposure may induce physical dependence, manifested as somatic withdrawal symptoms in the absence of th...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.10.015
更新日期:2008-03-01 00:00:00
abstract::The benzodiazepine--gamma-aminobutyric acid (GABA) receptor--ionophore system is an oligomeric complex, composed of at least three interacting components. These three components have been well characterized in vitro by radioreceptor binding assays. A variety of centrally acting anxiolytic, depressant, anticonvulsant a...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/0028-3908(83)90114-4
更新日期:1983-12-01 00:00:00
abstract::The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This res...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(91)90183-c
更新日期:1991-07-01 00:00:00
abstract::Schizophrenia is associated with increased oxidative stress, although the source of this redox disequilibrium requires further study. Altered tryptophan metabolism has been described in schizophrenia, possibly linked to inflammation and glutamate-directed excitotoxicity. Social isolation rearing (SIR) in rats induces ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.02.021
更新日期:2012-06-01 00:00:00
abstract::Stimulation of cannabinoid CB1 receptors or inhibition of nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (dlPAG) decreases anxiety-like behavior. Moreover, activation of CB1 receptors attenuates flight responses induced by nitric oxide (NO) donors in the dlPAG, suggesting that endocannabinoids and...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.07.008
更新日期:2013-12-01 00:00:00
abstract::The effect of acute exposure to alcohols on ion current mediated by recombinant 5-HT3RA receptors transiently expressed in human embryonic kidney 293 cells was investigated. Cells transfected with 5-HT3RA cDNA expressed receptors with pharmacological and functional properties similar to those of native 5-HT3 receptors...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)90131-7
更新日期:1994-12-01 00:00:00
abstract::Depolarizations provoked by acetylcholine (ACh) and three dicholines, succinylcholine (SCh), glutarylcholine (GCh) and azelainylcholine (AzCh) were measured in normal and 3-7 days denervated muscles of adult, and in normal muscles of 0-27 days old mice and rats. Soleus and flexor digitorum superficialis muscles were m...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(89)90032-4
更新日期:1989-04-01 00:00:00
abstract::The demonstrated functional interaction of metabotropic glutamate 5 (mGlu₅) receptors with N-methyl-d-aspartate (NMDA) receptors has prompted speculation that their activation may offer a potential treatment for aspects of schizophrenia. Development of selective mGlu₅ agonists has been difficult, but several different...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2012.07.030
更新日期:2013-01-01 00:00:00
abstract::Gliomas are the leading cause of cancer-related mortality worldwide, and the incidence is increasing. Because gliomas often become resistant to radiation treatment, it is urgent to develop novel therapeutic methods that are more effective and less toxic than current therapies so as to enhance patient survival and qual...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.05.009
更新日期:2015-02-01 00:00:00
abstract::The N-methyl-D-aspartate (NMDA) antagonist ifenprodil and several structurally related compounds are highly selective for the NR2B-containing receptor subtype. This selectivity could provide an explanation for the reported difference of the analgesic and side-effect profile of ifenprodil-like compounds from other NMDA...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00148-9
更新日期:2001-01-01 00:00:00
abstract::gamma-Aminobutyric acid (GABA, half-maximal inhibitory concentration, IC50 = 9.9 microM) and (-)-baclofen (IC50 = 4.5 microM) but not 10(-4) M muscimol, exerted a presynaptic inhibitory effect on cholinergic transmission in field-stimulated guinea-pig taenia coli preparations, in vitro. The antagonism by 10(-5) M (1S,...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(87)90012-8
更新日期:1987-11-01 00:00:00