Abstract：
:Despite evidence from psychiatry and psychology clinics pointing to altered cognition and decision making following the consumption of cannabis, the effects of cannabis derivatives are still under dispute and the mechanisms of cannabinoid effects on cognition are not known. In this study, we used effort-based and delay-based decision tasks and showed that ACEA, a potent cannabinoid agonist induced apathetic and impulsive patterns of choice in rats in a dose-dependent manner when locally injected into the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), respectively. Pre-treatment with AM251, a selective cannabinoid type 1 (CB1) receptor antagonist, reversed ACEA-induced impulsive and apathetic patterns of choice in doses higher than a minimally effective dose. Unlike CB1 receptor antagonist, pretreatment with capsazepine, a transient receptor potential vanilloid type 1 (TRPV1) channel antagonist, was effective only at an intermediary dose. Furthermore, capsazepine per se induced impulsivity and apathy at a high dose suggesting a basal tonic activation of TRPV1 channels that exist in the ACC and OFC to support cost-benefit decision making and to help avoid apathetic and impulsive patterns of decision making. Taken together, unlike previous reports supporting opposing roles for the CB1 receptors and TRPV1 channels in anxiety and panic behavior, our findings demonstrate a different sort of interaction between endocannabinoid and endovanilloid systems and suggest that both systems contribute to the cognitive disrupting effects of cannabinoids. Given prevalent occurrence of apathy and particularly impulsivity in psychiatric disorders, these results have significant implications for pharmacotherapy research targeting these receptors.
journal_name
Neuropharmacologyjournal_title
Neuropharmacologyauthors
Fatahi Z,Reisi Z,Rainer G,Haghparast A,Khani Adoi
10.1016/j.neuropharm.2018.01.021subject
Has Abstractpub_date
2018-05-01 00:00:00pages
75-84eissn
0028-3908issn
1873-7064pii
S0028-3908(18)30021-2journal_volume
133pub_type
杂志文章abstract：:Metabotropic glutamate receptor subtype 5 (mGluR5), encoded by the GRM5 gene, represents a compelling novel drug target for the treatment of schizophrenia. mGluR5 is a postsynaptic G-protein coupled glutamate receptor strongly linked with several critical cellular processes that are reported to be disrupted in schizop...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.08.003
更新日期：2017-03-15 00:00:00
abstract：:The heart rate of the anaesthetized rabbit was slowed by electrical stimulation of the hypothalamus with 7-9 sec trains of 250-330 microA pulses, duration 1 msec, frequency 60 Hz. This vagally-mediated cardio-decelerator response was attenuated in a dose-dependent manner after intravenous administration of phenoxybenz...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90258-7
更新日期：1983-01-01 00:00:00
abstract：:Selective serotonin (5-HT) re-uptake inhibitors (SSRIs) are commonly used in the treatment of generalized anxiety disorder in Humans. However, because only few animal models display overt anxious-like behavior, detailed preclinical studies of the anxiolytic properties of antidepressants are still lacking. Here, we stu...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2011.02.009
更新日期：2011-09-01 00:00:00
abstract：:The phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/Akt)/mechanistic target of rapamycin (mTOR) signaling pathway has been associated with several pathologies in the central nervous system (CNS), including epilepsy. There is evidence supporting the hypothesis that the PI3Kγ signaling pathway may mediate the...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2020.108156
更新日期：2020-10-01 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：:Tolcapone and entacapone are catechol-O-methyltransferase (COMT) inhibitors used as adjuncts to levodopa in the treatment of Parkinson's disease (PD). The use of tolcapone has been limited by its hepatotoxicity, the cause of which remains uncertain. Tolcapone compound is an uncoupler of mitochondrial respiration in is...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2003.10.015
更新日期：2004-03-01 00:00:00
abstract：:This paper evaluates the involvement of hippocampal ATP-sensitive potassium channels (K(ATP)) in learning and memory. After confirming expression of the Kir6.2 subunit in the CA3 region of C57BL/6J mice, we performed intra-hippocampal pharmacological injections of specific openers and blockers of K(ATP) channels. The ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.11.001
更新日期：2009-03-01 00:00:00
abstract：:Dietary supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including a possible reduction in cognitive decline in the elderly. Here we report that pre-treatment with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) significantly reduced the survi...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2008.02.003
更新日期：2008-05-01 00:00:00
abstract：:This study shows that the selective GABAB antagonist CGP 35348 had no effect on body temperature in mice in doses up to 300 mg/kg i.p. However, the highest dose abolished the hypothermia induced by the GABAB agonist baclofen (10 mg/kg i.p.) but not that produced by the GABA-mimetic progabide (200 mg/kg i.p.); the benz...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90018-7
更新日期：1991-05-01 00:00:00
abstract：:The effects of intracerebroventricular (i.c.v.) administration of NT on the activity of midbrain DA neurons were studied in rats using single unit recording techniques. NT (i.c.v., 50 micrograms) was found to have no significant effect on the spontaneous activity of DA cells. On the other hand, NT treatment significan...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(90)90119-c
更新日期：1990-11-01 00:00:00
abstract：:The effects of the dopamine antagonists haloperidol and sultopride were investigated on the twitch response, evoked by 0.1 Hz stimulation of guinea-pig isolated ileal longitudinal muscle, and on the inhibition of the twitch response induced by 10 Hz stimulation (post-tetanic twitch inhibition) and by application of op...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(94)00166-p
更新日期：1995-05-01 00:00:00
abstract：:In fixed tissue, neuronal NADPH-diaphorase staining results from nitric oxide synthase (NOS) activity. Neuronal NOS only synthesizes nitric oxide once activated by the binding of Ca2+/calmodulin. We show here that neuronal NADPH-diaphorase staining is also dependent on Ca2+/calmodulin, implying that only activated NOS...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(97)00159-7
更新日期：1997-11-01 00:00:00
abstract：:Interferon injection in morphine dependent rats prior to naloxone treatment eliminates 7 behavioral sings of the abstinence (withdrawal) phenomenon. When a single injection of interferon was given prior to chronic morphine treatment it reduces opiate addiction liability. ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(83)90157-0
更新日期：1983-05-01 00:00:00
abstract：:Histamine H3 receptor (H3R) antagonists are currently being investigated for the possible therapeutic use in various cognitive deficits such as those in schizophrenia, attention deficit hyperactivity disorder and Alzheimer's disease. Our previous studies suggest a role for H3Rs in ethanol-related behaviors in rat and ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2010.10.027
更新日期：2011-06-01 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：:The effects of phospholipase A2, cyclooxygenase-1, cyclooxygenase-2, and 5-lipoxygenase inhibitors on acute opiate withdrawal induced by selective mu, kappa and delta receptor agonists was investigated in vitro. After a 4 min in vitro exposure to D-Ala2-N-methyl-Phe-Gly5-ol)enkephalin (DAMGO; a highly selective mu ago...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(99)00004-0
更新日期：1999-06-01 00:00:00
abstract：:4-Phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) has previously been shown to have antagonistic properties to methamphetamine in the spinal cord. Administration of 4-PTIQ (5 mg/kg, s.c.) reduced the ambulation induced by methamphetamine (0.5 mg/kg, s.c.) in rats. Methamphetamine (3 micrograms), injected unilaterally i...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(93)90107-e
更新日期：1993-03-01 00:00:00
abstract：:Antipsychotic drug treatment increases neurotensin (NT) neurotransmission, and the exogenous administration of NT produces antipsychotic-like effects in rodents. In order to investigate whether "endogenous" NT may act as a natural occurring antipsychotic or may mediate antipsychotic drug activity, the effects of the s...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2004.03.001
更新日期：2004-07-01 00:00:00
abstract：:Hippocampal volume reductions and functional impairments are reliable findings in posttraumatic stress disorder (PTSD) imaging studies. However, it is not clear if and how hippocampal dysfunction contributes to the etiology and maintenance of PTSD. Individuals with PTSD are often described as showing fear responses to...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2011.04.029
更新日期：2012-02-01 00:00:00
abstract：:The effect of drugs which down-regulate the function of GABA at the level of the GABA/benzodiazepine receptor complex was studied on the conflict test in the rat. The GABA receptor antagonist, bicuculline, and the blockers of the GABA-receptor-coupled chloride channel, picrotoxin and pentylenetetrazol, produced a dose...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(86)90181-4
更新日期：1986-05-01 00:00:00
abstract：:Mutations in the X-linked cyclin-dependent kinase-like 5 (CDKL5) gene cause CDKL5 Deficiency Disorder (CDD), a rare neurodevelopmental syndrome characterized by severe behavioural and physiological symptoms. No cure is available for CDD. CDKL5 is a kinase that is abundantly expressed in the brain and plays a critical ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2018.10.018
更新日期：2019-01-01 00:00:00
abstract：:Pediatric traumatic brain injury (TBI) remains one of the leading causes of morbidity and mortality in children. Experimental and clinical studies demonstrate that the developmental age, the type of injury (diffuse vs. focal) and sex may play important roles in the response of the developing brain to a traumatic injur...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2018.06.025
更新日期：2019-02-01 00:00:00
abstract：:The metabotropic glutamate receptor (mGluR) agonist ACPD exerts an unusual inhibitory effect on a population of neurons of the song-control nucleus HVc of the zebra finch via activation of the GIRK channel. We report in the present study the pharmacology of this response. ACPD directly hyperpolarized the neurons by a ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/s0028-3908(98)00206-8
更新日期：1999-04-01 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
abstract：:We have previously demonstrated that an acute dose of Δ9-tetrahydrocanninbinol (THC), administered prior to extinction learning, facilitates later recall of extinction learning and modulates the underlying neural circuitry, including the ventromedial prefrontal cortex (vmPFC), hippocampus (HPC), and amygdala (AMYG). I...
journal_title：Neuropharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.neuropharm.2018.10.002
更新日期：2018-12-01 00:00:00
abstract：:Nicotinic acetylcholine receptors (nAChRs) are highly conserved between humans and non-human primates. Conservation exists at the level of genomic structure, protein structure and epigenetics. Overall homology of nAChRs at the protein level is 98% in macaques versus 89% in mice, which is highly relevant for evaluating...
journal_title：Neuropharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.neuropharm.2015.01.023
更新日期：2015-09-01 00:00:00
abstract：:Mefloquine continues to be a key drug used for malaria chemoprophylaxis and treatment, despite reports of adverse events like depression and anxiety. It is unknown how mefloquine acts within the central nervous system to cause depression and anxiety or why some individuals are more vulnerable. We show that intraperito...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.10.013
更新日期：2016-02-01 00:00:00
abstract：:The interest in the role of metabotropic glutamate receptor 4 (mGlu4) in CNS related disorders has increased the need for methods to investigate the binding of allosteric drug candidates. Our aim is to present the first fully characterized in vitro binding assay of mGlu4 positive allosteric modulators (PAMs). Results ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2015.05.017
更新日期：2015-10-01 00:00:00
abstract：:The purpose of the present studies was to investigate the behavioral and convulsant effects produced by the group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG). Administered i.c.v. to mice, (S)-3,5-DHPG produced a behavioral syndrome consisting of scratching and/or facial grooming, tr...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/j.neuropharm.2005.01.017
更新日期：2005-05-01 00:00:00
abstract：:The ability of specific dopamine (DA) receptor agonists and antagonists to modify the release and metabolism of DA in the ventrolateral striatum of awake rats was assessed using in vivo microdialysis. The specific DA D2 receptor antagonist, raclopride (0.1, 0.5 and 2.0 mg/kg, i.p.), dose-dependently increased release ...
journal_title：Neuropharmacology
pub_type： 杂志文章
doi：10.1016/0028-3908(91)90022-4
更新日期：1991-12-01 00:00:00
