Abstract:
:alpha(2)-ARs regulate brain monoaminergic function by inhibiting neuronal firing and release of monoamine neurotransmitters, noradrenaline (NA), serotonin (5-HT) and dopamine (DA). Both alpha(2A)- and alpha(2C)-AR inhibit monoamine release in vitro in brain slices, but the in vivo roles of individual alpha(2)-AR subtypes in modulating monoamine metabolism have not been characterised. Metabolism of brain monoamine neurotransmitters, locomotor activity and body temperature were investigated in mice with targeted inactivation of the gene encoding alpha(2A)-AR (alpha(2A)-knockout, alpha(2A)-KO) and wild-type (WT) mice after treatment with the alpha(2)-AR agonist dexmedetomidine and the antagonist atipamezole. Dexmedetomidine caused profound hypothermia (up to 14.7 degrees C mean reduction in rectal temperature) and locomotor inhibition in WT mice, and inhibited the turnover of NA, 5-HT and DA, but increased NA turnover in alpha(2A)-KO mice. alpha(2)-AR agonist-induced hypothermia and locomotor inhibition were attenuated, but not totally abolished, in alpha(2A)-KO mice. These results suggest that alpha(2A)-ARs are principally responsible for the alpha(2)-AR mediated inhibition of brain monoamine metabolism, but other alpha(2)-ARs, possibly alpha(2C)-ARs, are also involved, especially in the striatum. However, secondary effects of the physiological alterations caused by drug administration, especially hypothermia, may have contributed to the observed neurochemical changes in WT mice.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Lähdesmäki J,Sallinen J,MacDonald E,Sirviö J,Scheinin Mdoi
10.1016/s0028-3908(03)00080-7subject
Has Abstractpub_date
2003-06-01 00:00:00pages
882-92issue
7eissn
0028-3908issn
1873-7064pii
S0028390803000807journal_volume
44pub_type
杂志文章abstract::Endogenous interferon beta (IFNβ) is an important cytokine involved in several chronic inflammatory diseases, such as Multiple Sclerosis (MS). In spite of the numerous therapeutic approaches available for MS patients, the administration of recombinant IFNβ continues being one of the first line treatment to these patie...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.07.026
更新日期:2016-11-01 00:00:00
abstract::The ability of drugs of abuse to increase mesolimbic levels of dopamine is a characteristic associated with their rewarding effects. Exactly how these effects are produced by different substances is not as well characterised. Our previous work in rats has demonstrated that accumbal glycine receptors (GlyRs) are involv...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.03.010
更新日期:2014-07-01 00:00:00
abstract::The functional expression of H4 receptors (H4R) within neurons of the central nervous system has been recently reported, but their role is poorly understood. The present study aims to elucidate the role of neuronal H4R by providing the first description of the behavioural phenotype of H4R-deficient (H4R knockout, H4R-...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2016.11.023
更新日期:2017-03-01 00:00:00
abstract::Selective radioligands for histamine H(3) receptors have been used to characterize H(3) receptor pharmacology by radioligand binding assays and to determine H(3) receptor distribution by tissue autoradiography. Here we report the synthesis and receptor binding characterization of [(3)H]A-317920 (furan-2-carboxylic aci...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2005.10.008
更新日期:2006-03-01 00:00:00
abstract::The effects of thyrotropin-releasing hormone (TRH) were examined on the monosynaptic reflex and on the activity of motoneurons in the spinal cord of the neonatal rat to elucidate the mechanism of action of TRH and its ability to reverse the spinal depression caused by phencyclidine and ketamine. Phencyclidine (2-32 mi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(88)90061-5
更新日期:1988-10-01 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::Despite notable progress in recent decades, cigarette smoke persists as a leading cause of premature death and preventable disease. To weaken the link between nicotine reinforcement and the toxicity associated with combusted tobacco, the United States Food and Drug Administration is considering a product standard targ...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108200
更新日期:2020-09-15 00:00:00
abstract::Calcium currents in the inferior colliculus (IC) are thought to play an important role in ethanol withdrawal hyperexcitability. Here, we report on the modulation of Ca(2+) channel currents in acutely dissociated IC neurons of rats, exhibiting higher incidence of audiogenic seizures when subjected to ethanol withdrawal...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(03)00191-6
更新日期:2003-09-01 00:00:00
abstract::Time-effects of morphine, methadone, meperidine and pentazocine upon locomotor activity were investigated in naive and in post-dependent rats. Dependence was induced by daily injection of 20 mg/kg (i.p.) of morphine for 30 days. Tests were run starting from 1 month after withdrawal from morphine. Morphine produced a g...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(85)90041-3
更新日期:1985-09-01 00:00:00
abstract::Activation of microglia has been implicated in many neurological conditions including Alzheimer's disease and neuropathic pain. Recent studies provide evidence that P2X ATP receptors on the surface of microglia play a crucial role in initiation of inflammatory cascades. We investigated changes in surface P2X receptors...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.06.010
更新日期:2007-09-01 00:00:00
abstract::R(-)11-Hydroxy-N-n-propylnoraporphine (11-OH-NPa) induced stereotyped behavior in the rat as potently (ED50 = 0.80 mg/kg, i.p.) as R(-)apomorphine (APO) and this effect was blocked by haloperidol; the 11-methoxy congener, R(-)11-MeO-NPa, had a weak effect (ED50 greater than 10 mg/kg) and the S(+) isomers had none. The...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(90)90064-x
更新日期:1990-06-01 00:00:00
abstract::Intracerebroventricular administration of neurotensin (NT) suppresses locomotor activity. However, the brain regions that mediate the locomotor depressant effect of NT and receptor subtype-specific mechanisms involved are unclear. Using a brain-penetrating, selective NT receptor type 1 (NTS1) agonist PD149163, we inve...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2014.05.046
更新日期:2014-10-01 00:00:00
abstract::Compelling evidence has shown that in hippocampus tumor necrosis factor alpha (TNF-alpha) at pathological concentration inhibits long-term potentiation (LTP), a synaptic model of learning and memory. In the present work we investigated the role of TNF-alpha in LTP of C-fiber evoked field potentials in spinal dorsal ho...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.09.011
更新日期:2007-03-01 00:00:00
abstract::Post-traumatic stress disorder (PTSD) is characterized by avoidance of trauma-associated stimuli and amygdala hyperreactivity, and is highly co-morbid with alcohol use disorder (AUD). Our lab uses a predator odor (bobcat urine) stress model that produces conditioned avoidance of an odor-paired context in a subset of r...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2020.107979
更新日期:2020-04-01 00:00:00
abstract::The present experiments investigated the ability of LY392098, a novel positive allosteric modulator of AMPA receptors, to potentiate AMPA receptor-mediated currents of neurons in the prefrontal cortex (PFC). Co-application of LY392098 (0.03-10 microM) with AMPA (5 microM) enhanced current through AMPA receptor/channel...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00195-7
更新日期:2001-06-01 00:00:00
abstract::Neural sensorimotor gating mechanisms prevent the interruption of ongoing information processing routines by ensuing stimuli to permit mental integration and adaptive behavior. Prepulse inhibition (PPI), an operational measure of sensorimotor gating, is now being investigated using murine models to exploit transgenic ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(00)00030-7
更新日期:2000-08-23 00:00:00
abstract::The effects of guanosine-5'-triphosphate (GTP), sodium chloride and manganese chloride on the binding of buprenorphine to opiate receptors present in rat brain has been studied. Manganese chloride significantly decreased the affinity of binding of both [3H] buprenorphine and unlabelled buprenorphine to morphine and en...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90201-6
更新日期:1984-03-01 00:00:00
abstract::Over the last decade, robust human genetic findings have been instrumental in elucidating the heritable basis of nicotine addiction (NA). They highlight coding and synonymous polymorphisms in a cluster on chromosome 15, encompassing the CHRNA5, CHRNA3 and CHRNB4 genes, coding for three subunits of the nicotinic acetyl...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2020.108234
更新日期:2020-10-15 00:00:00
abstract::As postsynaptic metabotropic subtype 1 (mGlu1) receptors are present in the thalamus, we have investigated the effect of potentiating and antagonising mGlu1 receptors on responses of thalamic neurones to noxious sensory stimulation. Extracellular recordings were made in vivo with multi-barrel iontophoretic electrodes ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.12.016
更新日期:2014-04-01 00:00:00
abstract::Transgenic mice that accumulate Aβ peptides in the CNS are commonly used to interrogate functional consequences of Alzheimer's disease-associated amyloidopathy. In addition to changes to synaptic function, there is also growing evidence that changes to intrinsic excitability of neurones can arise in these models of am...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2013.09.004
更新日期:2014-04-01 00:00:00
abstract::Neonatal administration of monosodium glutamate (MSG) destroyed perikarya in the arcuate nucleus and median eminence, including those that contain met-enkephalin and beta-endorphin and it increased the density of opiate receptors in the midbrain. Treatment with glutamate decreased the analgesic response on the jump te...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(84)90231-4
更新日期:1984-10-01 00:00:00
abstract::High performance liquid chromatography with electrochemical detection (HPLC-EC) was adapted for the analysis of metabolites of monoamines (MA) in the developing brain of the rat. 3-Methoxy-4-hydroxy-phenyl-ethylene glycol (MOPEG), dihydroxy phenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxy-3-indoleaceti...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(86)90191-7
更新日期:1986-09-01 00:00:00
abstract::Prenatal hypoxia ischemia is a major cause of neurodevelopmental impairment in the newborn, associated with risk for motor, behavioral and cognitive impaired outcomes. We used an established mouse model of maternal hypoxia to examine the immediate molecular responses of signaling pathways associated with both cell dea...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2009.07.028
更新日期:2009-10-01 00:00:00
abstract::Clinically effective antidepressants are thought to exert their therapeutic effects by facilitating central monoamine neurotransmission. However, recent data showing that neurokinin-1 receptor (NK1R) antagonists have antidepressant properties in both animal and clinical studies raise the possibility that classical ant...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2004.02.013
更新日期:2004-06-01 00:00:00
abstract::In the present study, we investigated the effect of ACPT-I [(1S, 3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid], a blood-brain-barrier permeable agonist of group III mGlu receptor, against oxygen-glucose deprivation (OGD)-evoked neuronal cell death in primary neuronal cell cultures and in the model of transient ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2015.11.025
更新日期:2016-03-01 00:00:00
abstract::A cDNA encoding the human metabotropic glutamate receptor type 4 (hmGluR4) was isolated from human brain cDNA libraries by cross-hybridization with rat mGluR4 probes. The deduced amino acid sequence of human mGluR4 consists of 912 residues and shows a sequence identity of 96% to the amino acid sequence of rat mGluR4. ...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/0028-3908(94)00149-m
更新日期:1995-02-01 00:00:00
abstract::Attentional impairments are found in a range of neurodegenerative and neuropsychiatric disorders. However, the development of procognitive enhancers to alleviate these impairments has been hindered by a lack of comprehensive hypotheses regarding the circuitry mediating the targeted attentional functions. Here we discu...
journal_title:Neuropharmacology
pub_type: 杂志文章,评审
doi:10.1016/j.neuropharm.2012.06.060
更新日期:2013-01-01 00:00:00
abstract::The effect of an acute intraperitoneal (i.p.) injection of acetaldehyde, 20 mg/kg or 100 mg/kg, on the microdialysate content of both amino acids and monoamines was studies in the nucleus accumbens (NA) by a microdialysis technique. Acetaldehyde, ACH, which was detectable at levels of 50-130 mumol/g brain tissue 10 mi...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/s0028-3908(97)00007-5
更新日期:1997-02-01 00:00:00
abstract::N-methyl-D-aspartate (NMDA) receptors play several essential roles in the physiology and pathophysiology of the brain. Their activation results in long-term changes in glutamatergic synaptic transmission in several brain areas, but excessive activation of these receptors induces neurotoxicity. Some of NMDA-mediated ac...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2006.03.025
更新日期:2006-08-01 00:00:00
abstract::The role of orexin receptors in the nucleus accumbens shell in rat turning behaviour of rats was studied. Unilateral injection of neither the orexin 1 and 2 receptor agonist orexin A (2 microg) nor the orexin 1 receptor antagonist SB 334867 (20 ng) into the nucleus accumbens shell elicited turning behaviour. Unilatera...
journal_title:Neuropharmacology
pub_type: 杂志文章
doi:10.1016/j.neuropharm.2007.11.006
更新日期:2008-03-01 00:00:00