Abstract：
:Cocaine administration can be both rewarding and aversive. While much effort has gone to investigating the rewarding effect, the mechanisms underlying cocaine-induced aversion remain murky. There is increasing evidence that the lateral habenula (LHb), a small epithalamic structure, plays a critical role in the aversive responses of many addictive drugs including cocaine. However, the effects of cocaine on LHb neurons are not well explored. Here we show that, in acute brain slices from rats, cocaine depolarized LHb neurons and accelerated their spontaneous firing. The AMPA and NMDA glutamate receptor antagonists, 6, 7-dinitroquinoxaline-2, 3-dione, DL-2-amino-5-phosphono-valeric acid, attenuated cocaine-induced acceleration. In addition, cocaine concentration-dependently enhanced glutamatergic excitation: enhanced the amplitude but reduced the paired pulse ratio of EPSCs elicited by electrical stimulations, and increased the frequency of spontaneous EPSCs in the absence and presence of tetrodotoxin. Dopamine and the agonists of dopamine D1 (SKF 38393) and D2 (quinpirole) receptors, as well as the dopamine transporter blocker (GBR12935), mimicked the effects of cocaine. Conversely, both D1 (SKF83566) and D2 (raclopride) antagonists substantially attenuated cocaine's effects on EPSCs and firing. Together, our results provide evidence that cocaine may act primarily via an increase in dopamine levels in the LHb that activates both D1 and D2 receptors. This leads to an increase in presynaptic glutamate release probability and LHb neuron activity. This may contribute to the aversive effect of cocaine observed in vivo.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Zuo W,Chen L,Wang L,Ye JHdoi
10.1016/j.neuropharm.2013.01.008subject
Has Abstractpub_date
2013-07-01 00:00:00pages
180-9eissn
0028-3908issn
1873-7064pii
S0028-3908(13)00014-2journal_volume
70pub_type
杂志文章abstract：:The effects of the glycine derivative, CP 1552-S (2-N-pentylaminoacetamide hydrochloride) were evaluated for potential anticonvulsant activity in rats which were cortically- or amygdaloid-kindled. Large doses (300-600 mg/kg, i.p.) of CP 1552 given 30 min before stimulation resulted in significant reductions in duratio...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90012-1
更新日期：1984-08-01 00:00:00
abstract：:Dopamine neurons in the ventral tegmental area (VTA) play a very important role in a variety of physiological as well as addictive behaviors. However, a clear understanding of the cellular mechanisms underlying these behaviors is still missing. Within the VTA, recent studies have shown that forms of synaptic plasticit...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2008.07.024
更新日期：2009-01-01 00:00:00
abstract：:In rat brain, the number of beta-adrenoceptors and activity of noradrenaline-dependent adenylate cyclase were examined after treatment with desipramine (7.5 mg kg-1 day-1) for three days alone or in combination with the alpha 2-adrenoceptor antagonist, yohimbine (2 mg kg-1 12 hr-1), or with phenoxybenzamine (7.5 mg kg...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(84)90077-7
更新日期：1984-12-01 00:00:00
abstract：:Dopamine (DA) is a major catecholamine neurotransmitter in the mammalian brain that controls neural circuits involved in the cognitive, emotional, and motor aspects of goal-directed behavior. Accordingly, perturbations in DA neurotransmission play a central role in several neuropsychiatric disorders. Somewhat surprisi...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2017.04.033
更新日期：2017-09-15 00:00:00
abstract：RATIONALE:Diabetes mellitus (DM) is a major risk factor for Alzheimer's disease and vascular dementia. Few animal models exist that focus on the metabolic contributions to dementia onset and progression. Thus, there is strong scientific rationale to explore the effects of streptozotocin (STZ), a diabetogenic compound, ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.04.021
更新日期：2018-07-15 00:00:00
abstract：:Nicotine stimulates the secretion of catecholamines from sympathetic nerve endings and adrenal medulla by acting on peripheral nicotinic cholinergic receptors. Nicotine is also a potent stimulant in the central nervous system but the significance of nicotinic receptors in brain in mediating cardiovascular and sympatho...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90071-x
更新日期：1990-06-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2020.108130
更新日期：2020-08-15 00:00:00
abstract：:Amphetamine (AMPH) acts as a substrate of the dopamine transporter (DAT) and causes a dramatic increase in extracellular dopamine (DA). Upon entering DA neurons, AMPH promotes DA efflux via DAT through a mechanism implicating depletion of DA from vesicular stores, activation of kinase pathways and transporter phosphor...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.06.002
更新日期：2019-12-15 00:00:00
abstract：:Previously we have reported that astrocytes deprived of glucose were highly vulnerable to peroxynitrite (Choi and Kim, J. Neurosci. Res. 54 (1998) 870; Neurosci. Lett. 256 (1988) 109; Ju et al., J. Neurochem. 74 (2000) 1989). Here we report that ciclopirox, which is clinically used as an anti-fungal agent, completely ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(02)00081-3
更新日期：2002-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00075-1
更新日期：2000-01-01 00:00:00
abstract：:As a preliminary to positron emission tomography (PET) studies of excitatory amino acid neurotransmission, N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors of mice and rats were labelled in vivo with [3H]fluorothienylcyclohexylpiperidine [corrected] (FTCP), which binds to the phencyclidine site of the NMDA re...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90125-u
更新日期：1991-08-01 00:00:00
abstract：:Our recent studies have shown that the neuronal nitric oxide synthase (nNOS) gene is required for the development and persistence of psychomotor sensitization to cocaine in adult but not adolescent male mice (Balda, M.A., Anderson, K.L., Itzhak, Y., 2008. Differential role of the nNOS gene in the development of behavi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.12.004
更新日期：2009-03-01 00:00:00
abstract：:The importance of h5-HT1B receptor selectivity for 5-HT terminal autoreceptor activity was investigated with the selective h5-HT1B receptor ligands SB 219085, SB 220272, SB 224289 and SB 216641. The studies employed measurement of compound affinity and efficacy in vitro and the measurement of extracellular 5-HT in the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00026-9
更新日期：1997-04-01 00:00:00
abstract：:The cyclic octapeptide, CYN-154806, inhibited specific [(125)I]-[Tyr(11)]-SRIF binding to CHO-K1 cell membranes expressing human recombinant somatostatin (SRIF) sst(2) receptors (pIC(50) 8. 58) or rat sst(2(a)) and rat sst(2(b)) receptors (pIC(50) 8.35 and 8. 10, respectively). The affinity of CYN-154806 at other huma...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(00)00035-6
更新日期：2000-06-08 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90090-0
更新日期：1986-07-01 00:00:00
abstract：:The effects of microiontophoretically-applied and pneumatically-applied morphine on the spontaneous discharge of Purkinje cells in the cerebellum of the anesthetized cat were examined. Microiontophoretic application of morphine produced both inhibitory and excitatory responses of the Purkinje cells. Pneumatic applicat...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(89)90098-1
更新日期：1989-03-01 00:00:00
abstract：:Mice were injected bilaterally into the septum with 6-hydroxydopamine and 6 weeks later the hippocampi were assayed for activity of choline acetyltransferase, muscarinic receptor binding capabilities and for formation of inositol phosphate in response to direct (carbachol) or presynaptically elicited (K+) stimulation ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90090-p
更新日期：1993-02-01 00:00:00
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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
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2019.03.005
更新日期：2019-05-15 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.05.008
更新日期：2011-09-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2014.09.024
更新日期：2015-02-01 00:00:00
abstract：:Antiepileptic drugs (AEDs) are widely utilized in the management of neuropathic pain. The AED valproic acid (VPA) holds out particular promise as it engages a variety of different anticonvulsant mechanisms simultaneously. However, the clinical use of VPA is limited by two rare but potentially life-threatening side eff...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.06.008
更新日期：2005-12-01 00:00:00
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journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108414
更新日期：2021-02-15 00:00:00
abstract：:Benzodiazepines (BZDs) and barbiturates exert their CNS actions by binding to GABA-A receptors (GABARs). The structural mechanisms by which these drugs allosterically modulate GABAR function, to either enhance or inhibit GABA-gated current, are poorly understood. Here, we used the substituted cysteine accessibility me...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.11.009
更新日期：2011-02-01 00:00:00
abstract：:Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through wh...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.08.033
更新日期：2019-01-01 00:00:00
abstract：:Administration of stimulant and non-stimulant drugs that inhibit monoamine reuptake is known to improve cognitive and behavioral symptoms of attention deficit hyperactivity disorder (ADHD). Although this may reflect acute actions of these drugs, clinical observations suggest that prolonged treatment with these agents ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2009.08.007
更新日期：2009-12-01 00:00:00
abstract：:Phosphodiesterase 2 (PDE2) plays an important role in treatment of stress-related depression through regulation of antioxidant defense and neuroprotective mechanisms. However, the causal relationship between PDE2 and the prevalence of depression and anxiety upon exposure to oxidative stress has not been investigated. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.09.039
更新日期：2018-12-01 00:00:00
abstract：:Anandamide and 2-arachidonoyl glycerol, referred to as endocannabinoids (eCBs), are the endogenous agonists for the cannabinoid receptor type 1 (CB1). Several pieces of evidence support a role for eCBs in the attenuation of anxiety-related behaviours, although the precise mechanism has remained uncertain. The fatty ac...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2007.07.005
更新日期：2008-01-01 00:00:00
abstract：:The effect of chronic (4 weeks) treatment of rats with the antidepressant drugs desipramine, maprotiline, chlorimipramine, zimelidine or iprindol on the sensitivity of presynaptic alpha 2- and postsynaptic beta-adrenoceptors in neocortical slices was investigated. Acute (1 day) treatment with the antidepressants did n...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(84)80002-7
更新日期：1984-02-01 00:00:00
abstract：:The sleeping time induced by thiopentone in rats was markedly prolonged by the (-)-isomer of propranolol while the (+)-isomer was virtually without effect. Since the two isomers are equipotent in their membrane-stabilizing effects but the (-)-isomer is about seven to ten times more potent than the (+)-isomer in beta-b...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90026-6
更新日期：1983-09-01 00:00:00
