共查询到6条相似文献,搜索用时 15 毫秒
1.
Romina Mizrahi Ivonne Suridjan Miran Kenk Tony P George Alan Wilson Sylvain Houle Pablo Rusjan 《Neuropsychopharmacology》2013,38(4):673-682
A number of addictions have been linked with decreased striatal dopamine (DA) receptor availability and DA release. Stress has a key role in cannabis craving, as well as in modulation of dopaminergic signaling. The present study aimed to assess DA release in response to a laboratory stress task with [11C]-(+)-PHNO positron emission tomography in cannabis users (CU). Thirteen healthy CU and 12 healthy volunteers (HV) were scanned during a sensorimotor control task (SMCT) and under a stress condition using the validated Montreal imaging stress task (MIST). The simplified reference tissue model (SRTM) was used to obtain binding potential (BPND) in striatal subdivisions: limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST). Stress-induced DA release (indexed as a percentage of reduction in [11C]-(+)-PHNO BP ND) between CU and HV was tested with analysis of variance. SMCT BPND was significantly higher in CU compared with HV in the AST (F=10.38, p=0.003), LST (F=4.95, p=0.036), SMST (F=4.33, p=0.048), and whole striatum (F=9.02, p=0.006). Percentage of displacement (change in BPND between SMCT and MIST PET scans) was not significantly different across groups in any brain region, except in the GP (−5.03±14.6 in CU, compared with 6.15±12.1 in HV; F=4.39, p=0.049). Duration of cannabis use was significantly associated with stress-induced [11C]-(+)-PHNO displacement by endogenous DA in the LST (r=0.566, p=0.044), with no effect in any other brain region. In conclusion, despite an increase in striatal BPND observed during the control task, chronic cannabis use is not associated with alterations in stress-induced DA release. 相似文献
2.
Jean-Dominique Gallezot Tracy Kloczynski David Weinzimmer David Labaree Ming-Qiang Zheng Keunpoong Lim Eugenii A Rabiner Khanum Ridler Brian Pittman Yiyun Huang Richard E Carson Evan D Morris Kelly P Cosgrove 《Neuropsychopharmacology》2014,39(4):866-874
The radiotracer [11C]PHNO may have advantages over other dopamine (DA) D2/D3 receptor ligands because, as an agonist, it measures high-affinity, functionally active D2/D3 receptors, whereas the traditionally used radiotracer [11C]raclopride measures both high- and low-affinity receptors. Our aim was to take advantage of the strength of [11C]PHNO for measuring the small DA signal induced by nicotine, which has been difficult to measure in preclinical and clinical neuroimaging studies. Nicotine- and amphetamine-induced DA release in non-human primates was measured with [11C]PHNO and [11C]raclopride positron emission tomography (PET) imaging. Seven adult rhesus monkeys were imaged on a FOCUS 220 PET scanner after injection of a bolus of [11C]PHNO or [11C]raclopride in three conditions: baseline; preinjection of nicotine (0.1 mg/kg bolus+0.08 mg/kg infusion over 30 min); preinjection of amphetamine (0.4 mg/kg, 5 min before radiotracer injection). DA release was measured as change in binding potential (BPND). Nicotine significantly decreased BPND in the caudate (7±8%), the nucleus accumbens (10±7%), and in the globus pallidus (13±15%) measured with [11C]PHNO, but did not significantly decrease BPND in the putamen or the substantia nigra or in any region when measured with [11C]raclopride. Amphetamine significantly reduced BPND in all regions with both radiotracers. In the striatum, larger amphetamine-induced changes were detected with [11C]PHNO compared with [11C]raclopride (52–64% vs 33–35%, respectively). We confirmed that [11C]PHNO is more sensitive than [11C]raclopride to nicotine- and amphetamine-induced DA release. [11C]PHNO PET may be more sensitive to measuring tobacco smoking-induced DA release in human tobacco smokers. 相似文献
3.
Nina BL Urban Ragy R Girgis Peter S Talbot Lawrence S Kegeles X Xu W Gordon Frankle Carl L Hart Mark Slifstein Anissa Abi-Dargham Marc Laruelle 《Neuropsychopharmacology》2012,37(6):1465-1473
3,4-Methylenedioxymethamphetamine (MDMA), the main psychoactive component of the recreational drug ecstasy, is a potent serotonin (5-HT) releaser. In animals, MDMA induces 5-HT depletion and toxicity in 5-HT neurons. The aim of this study was to investigate both presynaptic (5-HT transporter, SERT) and postsynaptic (5-HT2A receptor) markers of 5-HT transmission in recently abstinent chronic MDMA users compared with matched healthy controls. We hypothesized that MDMA use is associated with lower SERT density and concomitant upregulation of 5-HT2A receptors. Positron emission tomography studies using the SERT ligand [11C]DASB and the 5-HT2A receptor ligand [11C]MDL 100907 were evaluated in 13 current and recently detoxified MDMA users and 13 matched healthy controls. MDMA users reported a mean duration of ecstasy use of 8 years, regular exposure, and at least 2 weeks of abstinence before the scans. SERT and 5-HT2A receptor availability (binding potential, BPND) were analyzed with a two-tissue compartment model with arterial input function. Current recreational MDMA use was significantly associated with lower SERT BPND and higher 5-HT2A receptor BPND in cortical, but not subcortical regions. Decreased SERT BPND was regionally associated with upregulated 5-HT2A receptor BPND. In light of the animal literature, the most parsimonious interpretation is that repeated exposure to MDMA in humans, even in moderate amounts, leads to damage in 5-HT neuron terminals innervating the cortex. Alterations in mood, cognition, and impulse control associated with these changes might contribute to sustain MDMA use. The reversibility of these changes upon abstinence remains to be firmly established. 相似文献
4.
Romina Mizrahi Miran Kenk Ivonne Suridjan Isabelle Boileau Tony P George Kwame McKenzie Alan A Wilson Sylvain Houle Pablo Rusjan 《Neuropsychopharmacology》2014,39(6):1479-1489
Research on the environmental risk factors for schizophrenia has focused on either psychosocial stress or drug exposure, with limited investigation of their interaction. A heightened dopaminergic stress response in patients with schizophrenia and individuals at clinical high risk (CHR) supports the dopaminergic sensitization hypothesis. Cannabis is believed to contribute to the development of schizophrenia, possibly through a cross-sensitization with stress. Twelve CHR and 12 cannabis-using CHR (CHR-CU, 11 dependent) subjects underwent [11C]-(+)-PHNO positron emission tomography scans, while performing a Sensorimotor Control Task (SMCT) and a stress condition (Montreal Imaging Stress task). The simplified reference tissue model was used to obtain binding potential relative to non-displaceable binding (BPND) in the whole striatum, its functional subdivisions (limbic striatum (LST), associative striatum (AST), and sensorimotor striatum (SMST)), globus pallidus (GP), and substantia nigra (SN). Changes in BPND, reflecting alterations in synaptic dopamine (DA) levels, were tested with analysis of variance. SMCT BPND was not significantly different between groups in any brain region (p>0.21). Although stress elicited a significant reduction in BPND in the CHR group, CHR-CU group exhibited an increase in BPND. Stress-induced changes in regional BPND between CHR-CU and CHR were significantly different in AST (p<0.001), LST (p=0.007), SMST (p=0.002), SN (p=0.021), and whole striatum (p=0.001), with trend level in the GP (p=0.099). All subjects experienced an increase in positive (attenuated) psychotic symptoms (p=0.001) following the stress task. Our results suggest altered DA stress reactivity in CHR subjects who concurrently use cannabis, as compared with CHR subjects. Our finding does not support the cross-sensitization hypothesis, which posits greater dopaminergic reactivity to stress in CHR cannabis users, but adds to the growing body of literature showing reduced DA (stress) response in addiction. 相似文献
5.
Luca Ferraro Malgorzata Frankowska Daniel Marcellino Magdalena Zaniewska Sarah Beggiato Malgorzata Filip Maria Cristina Tomasini Tiziana Antonelli Sergio Tanganelli Kjell Fuxe 《Neuropsychopharmacology》2012,37(8):1856-1866
Recent in vitro results suggest that cocaine may exert direct and/or indirect allosteric enhancing actions at dopamine (DA) D2 receptors (D2Rs). In the present paper we tested the hypothesis that cocaine in vivo can enhance the effects of the D2-likeR agonist quinpirole in rats by using microdialysis and pharmacological behavioral studies. Furthermore, in vitro D2-likeR binding characteristics and Gαi/o-protein coupling, in the absence and in the presence of cocaine, have been investigated in rat striatal membranes. Intra-nucleus accumbens perfusion of the D2-likeR agonist quinpirole (10 μM) reduced local dialysate glutamate levels, whereas cocaine (10 and 100 nM) was ineffective. At a low concentration (100 nM), cocaine significantly enhanced quinpirole-induced reduction of accumbal extracellular glutamate levels. The behavioral experiments showed that cocaine (0.625 mg/kg), but not the DA uptake blocker GBR 12783 (1.25 mg/kg), enhanced quinpirole (1 mg/kg)-induced hyperlocomotion. Finally, cocaine (100 nM), but not GBR 12783 (200 nM), produced a small, but significant increase in the efficacy of DA to stimulate binding of GTPγS to striatal D2-likeRs, whereas the D2-likeR binding characteristics were unchanged in striatal membranes by cocaine in the nM range. The significant increase in the maximal response to DA-stimulated GTPγS binding to D2-likeRs by 100 nM cocaine remained in the presence of GBR 12783. The observed cocaine-induced enhancement of the Gαi/o-protein coupling of D2Rs may be in part because of allosteric direct and/or indirect enhancing effects of cocaine at these receptors. These novel actions of cocaine may have relevance for understanding the actions of cocaine upon accumbal DA, and/or glutamate transmission and thus its rewarding as well as relapsing effects. 相似文献
6.
Yi-Wei Yeh Pei-Shen Ho Chun-Yen Chen Shin-Chang Kuo Chih-Sung Liang Kuo-Hsing Ma Chyng-Yann Shiue Wen-Sheng Huang Cheng-Yi Cheng Tzu-Yun Wang Ru-Band Lu San-Yuan Huang 《The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)》2015,18(3)