Abstract:
:Cytochrome P450 2D (CYP2D) mediates the activation and inactivation of several classes of psychoactive drugs, including opioids, which can alter drug response. Tramadol is a synthetic opioid with analgesic activity of its own as well as being metabolically activated by CYP2D to O-desmethyltramadol (ODMST) an opioid receptor agonist. We investigated the impact of brain CYP2D metabolism on central tramadol and ODSMT levels, and resulting analgesic response after oral tramadol administration in rats. CYP2D inhibitors propranolol and propafenone were administered intracerebroventricularly prior to oral tramadol administration and analgesia was measured by tail-flick latency. Drug levels of tramadol and its metabolites, ODSMT and N-desmethyltramadol, were assessed in plasma and in brain by microdialysis using LC-ESI-MS/MS. Inhibiting brain CYP2D with propafenone pretreatment increased analgesia after oral tramadol administration (ANOVA p = 0.02), resulting in a 1.5-fold increase in area under the analgesia-time curve (AUC0-60, p < 0.01). This effect was associated with changes in the brain levels of tramadol and its metabolites consistent with brain CYP2D inhibition. In conclusion, under oral tramadol dosing pretreatment with a central administration of the CYP2D inhibitor propafenone increased analgesia (without altering plasma drug or metabolite levels), indicating that tramadol itself (and activity of CYP2D within the brain) contributed to analgesia.
journal_name
Brain Res Bulljournal_title
Brain research bulletinauthors
McMillan DM,El-Sherbeni AA,Richards J,Tyndale RFdoi
10.1016/j.brainresbull.2020.09.001subject
Has Abstractpub_date
2020-11-01 00:00:00pages
400-406eissn
0361-9230issn
1873-2747pii
S0361-9230(20)30623-7journal_volume
164pub_type
杂志文章abstract:OBJECTIVE:To explore the unified and disease specific structural features of the brain in patients spanning six mental disorders who experience own-thought auditory verbal hallucinations (OTAVH). METHODS:A pilot study was conducted on 25 patients with schizophrenia (FUSCH-OTAVH), 20 patients with major depression diso...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2020.04.001
更新日期:2020-07-01 00:00:00
abstract::The vertebrate neural tube consists of a series of neuromeres along its anteroposterior axis. Between amphioxus that possesses no neuromeres and gnathostomes, the lamprey occupies a critical position in the phylogeny for the origin of the segmented brain. To clarify the rhombomeric configuration of the Japanese lampre...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(01)00669-4
更新日期:2002-02-01 00:00:00
abstract::To assess the efficacy of using an HRP-coated wire knife to label cells of origin of cut axons, labeling cuts were made both through and parallel to the dorsal noradrenergic bundle. The damage to the dorsal bundle was evaluated independently by using fluorescence microscopy to detect the buildup of norepinephrine in c...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(82)90050-8
更新日期:1982-02-01 00:00:00
abstract::The effects of zinc, the N-methyl-D-aspartate glutamate receptor inhibitor, were studied in mice and rats using the forced swim test. Zinc (ZnSO4) in a dose of 30 mg/kg and imipramine (30 mg/kg), reduced the immobility time in the forced swim test in both species. Moreover, combined treatment in this test with zinc an...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(01)00473-7
更新日期:2001-05-15 00:00:00
abstract::Growing interest in cholinergic neuronal systems has caused a resurgence of thiocholine histochemical studies. Reports from different laboratories refer to "modified" Koelle-Friedenwald procedures for the histochemical localization of acetylcholinesterase (AChE) but the modifications are seldom specified. A glance at ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(84)90170-9
更新日期:1984-05-01 00:00:00
abstract::Methylphenidate (MPD), commonly known as Ritalin, is the most frequently prescribed drug to treat children and adults with attention deficit hyperactivity disorder (ADHD). Adolescence is a period of development involving numerous neuroplasticities throughout the central nervous system (CNS). Exposure to a psychostimul...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2006.09.019
更新日期:2006-12-11 00:00:00
abstract::Thyroid hormones are essential for neonatal brain development. It is well established that absence of thyroid hormones during critical periods of development can alter sensory functions such as visual and auditory processing, but there are few studies on rat somatosensory system development at mild, long-term, and irr...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2019.11.015
更新日期:2020-02-01 00:00:00
abstract::The glutamatergic system is an important target in many neurodegenerative diseases and for several neurotoxic drugs. Organotellurium compounds are often very good free radical scavengers' agents. Recently, we reported that diethyl-2-phenyl-2-tellurophenyl vinylphosphonate is a compound with low toxicity in vitro and i...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2007.12.008
更新日期:2008-05-15 00:00:00
abstract::Emerging evidence suggests that sleep deprivation (SD) is a public health epidemic and increase the risk of Alzheimer's disease (AD) progression. However, the underlying mechanisms remain to be fully investigated. In this study, we investigate the impact of 72 h SD on the prefrontal cortex (PFC) of 3∼4-months-old APP/...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2020.11.003
更新日期:2021-01-01 00:00:00
abstract::We studied the effects of estradiol (E2) and progesterone (P) on progesterone receptor (PR) isoforms gene expression in the brain of ovariectomised female and gonadectomised male rats by RT-PCR analysis. In female rats, the expression of both PR isoforms was induced by E2 and down-regulated by P in the hypothalamus, w...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(02)00845-6
更新日期:2002-10-30 00:00:00
abstract::Glutamate afferents reaching the ventral tegmental area (VTA) affect dopamine (DA) cells in this structure probably mainly via NMDA receptors. VTA appears to be one of the structures involved in regulation of hippocampal theta rhythm, and this work aimed at assessing the role of glutamatergic activation of the VTA in ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2014.06.001
更新日期:2014-08-01 00:00:00
abstract::Single units were recorded bilaterally from the caudate nuclei of cats before and after 50 microliter injections of either Merlis solution or L-DOPA (200 microgram) dissolved in Merlis into the left lateral cerebral ventricle. After injection of L-DOPA, but not Merlis solution, there was a period of unit silence in bo...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(77)90083-1
更新日期:1977-07-01 00:00:00
abstract::The availability of mutant mice that lack either MAO A or MAO B has created unique profiles in the central and peripheral availability of serotonin, norepinephrine, dopamine, and phenylethylamine. This paper summarizes some of the current known phenotypic findings in MAO A knock-out mice and contrast these with those ...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(01)00613-x
更新日期:2001-11-15 00:00:00
abstract::Glaucoma is no longer viewed simply as elevated intraocular pressure (IOP) that damages the optic nerve. In addition to high IOP, evidence is rapidly accumulating that suggests damage to the optic nerve may be initiated or sustained by any number of factors including ischemia, excitotoxicity, neurotrophin insufficienc...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/S0361-9230(03)00074-1
更新日期:2004-02-15 00:00:00
abstract::Scientific reports suggest that the exposure to long-term stressors throughout or during late gestation increase anxiety- and depression-like behaviors of offspring in their later life. Moreover, several studies concluded that increasing age correlates with increased anxiety behaviors in humans and rodents. In the pre...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2011.08.015
更新日期:2012-02-10 00:00:00
abstract::Injection of colchicine into the lateral ventricles (ICV) of rats results in a selective loss of neurons immunoreactive for choline acetyltransferase (ChAT) in the medial septum (MS) and a concomitant loss of acetylcholinesterase (AChE) positive fibers in the hippocampus. To determine if this loss of cholinergic cells...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(92)90132-h
更新日期:1992-11-01 00:00:00
abstract::Although interleukin-1β (IL-1β) is a prototypical pro-inflammatory cytokine, the specific mechanisms underlying the role of its cognate receptor, the interleukin-1 receptor (IL-1R) in peripheral sensitization remain to be investigated. Since emerging evidence in the literature indicates that IL-1β can modulate membran...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2017.01.019
更新日期:2017-04-01 00:00:00
abstract::There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brai...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2004.12.007
更新日期:2005-03-15 00:00:00
abstract::Root-spinal cord regeneration was investigated in immature and adult rats. The elongation in the dorsal root of regrowing dorsal root axons, rerouted ventral root nerve fibres (cholinergic neurons) or hypogastric nerve fibres (catecholaminergic neurons) is impeded as they meet the astrocyte dominated CNS tissue of the...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(89)90133-0
更新日期:1989-01-01 00:00:00
abstract::When applied by iontophoresis onto single sympathetic preganglionic neurones in the intermediolateral nucleus of segments T1-T3 in the cat, oxytocin and vasopressin each had an excitatory effect. This effect consisted of a prolonged (30-300 sec) after-discharge following termination of application. These results indic...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(84)90201-6
更新日期:1984-11-01 00:00:00
abstract::Human autopsy brain tissue is widely used to study neurodegenerative diseases such as Alzheimer's, Parkinson's and other diseases. However, when it comes to an evaluation of data obtained from such tissue, it is essential to consider potential postmortem effects on protein composition, posttranslational modification a...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2016.01.005
更新日期:2016-03-01 00:00:00
abstract::Songbirds have emerged as extremely important animals for investigating sex steroid hormone effects on the central nervous system. The masculinizing effects of exogenous estrogen on the neural circuits controlling song in female zebra finches are well documented. There is evidence that estrogens are necessary for the ...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/s0361-9230(97)00215-3
更新日期:1997-01-01 00:00:00
abstract::Degenerating terminals were mapped by the Fink-Heimer method after lateral or fourth ventricular administration of 6-hydroxydopamine (60OHDA). This method marks dopaminergic terminals and has the advantage that noradrenergic terminals are not stained. Fink-Heimer stained degeneratig terminals were seen bilaterally in ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/s0361-9230(80)80013-x
更新日期:1980-07-01 00:00:00
abstract::Early developmental abnormalities affecting mesocortical dopamine (DA) neurons may result in later functional deficits that play a role in the emergence of psychiatric illness in adolescence/early adulthood. Little is known about the functional maturation of these neurons under either normal or abnormal conditions. In...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2009.01.012
更新日期:2009-04-29 00:00:00
abstract::Field-evoked potentials from the main olfactory bulb in response to stimulation of the olfactory nerve and lateral olfactory tract were measured without and with conditioning stimulation of the locus coeruleus noradrenergic system. The locus coeruleus conditioning stimulus suppressed or inhibited the late components o...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(87)90213-9
更新日期:1987-06-01 00:00:00
abstract::Spinal cord ischemia-reperfusion injury(SCII)affects nerve function through many mechanisms, which are complex and not fully understood. Recently, accumulating evidence has indicated that long noncoding RNAs (lncRNAs) play an increasingly important role in SCII. We investigated the role of lncRNA growth arrest-specifi...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2020.12.005
更新日期:2020-12-11 00:00:00
abstract::To acquire knowledge about the environment two types of learning are necessary: declarative localizatory learning about where environmental cues and the subject are, and procedural learning about how to explore and move around the environment. Experimental data indicate that hippocampal regions are involved in spatial...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2006.06.006
更新日期:2006-10-16 00:00:00
abstract::Deep hypothermic circulatory arrest in cardiothoracic surgery evokes severe brain damages. On the other hand, blood pressure stimuli discontinuation to the brain has been found to induce alterations in neurotransmitter release, including glutamate, in numerous brain regions. Furthermore, it is well established that ex...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/j.brainresbull.2008.11.006
更新日期:2009-04-29 00:00:00
abstract::The contribution deals with the distribution of alkaline phosphatase and 5-nucleotidase in the medulla oblongata of Taphozous melanopogon (a Microchiroptera), for the first time. The main highlights of the study are: (1) Cranial nerve nuclei demonstrate intense activity of alkaline phosphatase, whereas except nucleus ...
journal_title:Brain research bulletin
pub_type: 杂志文章
doi:10.1016/0361-9230(79)90030-3
更新日期:1979-07-01 00:00:00
abstract::A high proportion of patients who have suffered a stroke also suffer from aphasia. Approximately half of those affected will remain in this state despite intensive language therapy. Non-invasive brain stimulation allows us to directly and focally stimulate areas of the brain. Repetitive transcranial magnetic stimulati...
journal_title:Brain research bulletin
pub_type: 杂志文章,评审
doi:10.1016/j.brainresbull.2013.07.005
更新日期:2013-09-01 00:00:00