Abstract：
:G-protein coupled dopamine and metabotropic glutamate receptors (mGlu) can modulate neurotransmission during Parkinson's disease (PD)-like neurodegeneration. PET imaging studies in a unilateral dopamine denervation model (6-OHDA) showed a significant inverse correlation of presynaptic mGlu4 and postsynaptic mGlu5 expression in the striatum and rapidly declining mGlu4 and enhanced mGlu5 expression in the hippocampus during progressive degeneration over time. Immunohistochemical studies verified the decreased mGlu4 expression in the hippocampus on the lesion side but did not show difference in mGlu5 expression between lesion and control side. Pharmacological MRI studies showed enhanced hemodynamic response in several brain areas on the lesion side compared to the control side after challenge with mGlu4 positive allosteric modulator or mGlu5 negative allosteric modulator. However, mGlu4 response was biphasic having short enhancement followed by negative response on both sides of brain. Studies in mGlu4 expressing cells demonstrated that glutamate induces cooperative increase in binding of mGlu4 ligands - especially at high glutamate levels consistent with in vivo concentration. This suggests that mGlu allosteric modulators as drug candidates will be highly sensitive to changes in glutamate concentration and hence metabolic state. These experiments demonstrate the importance of the longitudinal imaging studies to investigate temporal changes in receptor functions to obtain individual response for experimental drugs.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Jenkins BG,Zhu A,Poutiainen P,Choi JK,Kil KE,Zhang Z,Kuruppu D,Aytan N,Dedeoglu A,Brownell ALdoi
10.1016/j.neuropharm.2015.11.010subject
Has Abstractpub_date
2016-09-01 00:00:00pages
462-73eissn
0028-3908issn
1873-7064pii
S0028-3908(15)30174-Xjournal_volume
108pub_type
杂志文章abstract：:This study utilised the selective 5-ht(5A) receptor antagonist, SB-699551-A (3-cyclopentyl-N-[2-(dimethylamino)ethyl]-N-[(4'-{[(2-phenylethyl)amino]methyl}-4-biphenylyl)methyl]propanamide dihydrochloride), to investigate 5-ht5A receptor function in guinea pig brain. SB-699551-A competitively antagonised 5-HT-stimulate...
journal_title：Neuropharmacology
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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
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journal_title：Neuropharmacology
pub_type： 杂志文章
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abstract：:E2020 is a piperidine cholinesterase inhibitor (ChEI) which is structurally distinct from other compounds presently under study for treatment of Alzheimer's disease. We studied the effect of this compound on acetylcholine (ACh), norepinephrine (NE), dopamine (DA) and serotonin (5-HT; 5-hydroxytryptamine) by means of t...
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
pub_type： 杂志文章
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journal_title：Neuropharmacology
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journal_title：Neuropharmacology
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abstract：:Long-term L-DOPA treatment for Parkinson's disease (PD) is limited by motor complications, particularly L-DOPA-induced dyskinesia (LID). A therapy with the ability to ameliorate LID without reducing anti-parkinsonian benefit would be of great value. We assessed the ability of TC-8831, an agonist at nicotinic acetylcho...
journal_title：Neuropharmacology
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abstract：:The group II metabotropic glutamate receptor (mGluR) antagonists LY341495 and LY366457 were profiled for their effects on locomotor activity in mice. Both compounds significantly increased locomotor activity. Observational studies showed that rearing was also selectively increased. LY366457-induced hyperactivity was s...
journal_title：Neuropharmacology
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abstract：:The serotonergic system is known to modulate and mediate many of the central nervous system effects of stress. Here we investigated the ability of serotonergic agents to reverse the inhibition of the induction of hippocampal long-term potentiation (LTP) caused by prior exposure to inescapable stress. Elevated platform...
journal_title：Neuropharmacology
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abstract：:The nucleus tractus solitarius (NTS) region in the rat has been shown to receive arginine vasopressin (AVP) and oxytocin (OT) neurophysin-containing neuronal projections from the suprachiasmatic (SNC) and paraventricular nucleus (PVN). Thus, vasopressin and oxytocin might have central influences on the circulation. Th...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(82)90012-0
更新日期：1982-07-01 00:00:00
abstract：:Neurotensin (NTS) is a neuropeptide neurotransmitter expressed in the central and peripheral nervous systems. Many studies over the years have revealed a number of roles for this neuropeptide in body temperature regulation, feeding, analgesia, ethanol sensitivity, psychosis, substance use, and pain. This review provid...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108005
更新日期：2020-05-01 00:00:00
