Dataset Information

Balanced modulation of striatal activation from D2 /D3 receptors in caudate and ventral striatum: Disruption in cannabis abusers.

ABSTRACT: Proper communication between dorsal caudate (CD) and ventral striatum (VS) is likely to be crucial for on-time responses and its disruption might result in impulsivity. Here, we used functional magnetic resonance imaging (fMRI) with a sensorimotor reaction time task and positron emission tomography (PET) with [(11)C]raclopride in 14 healthy controls and 18 cannabis abusers to contrast the modulation of striatal fMRI responses by dopamine receptors (D2 /D3 R) in CD and VS. In controls, we show that the fMRI signals in VS that occurs concomitantly with on-time responses showed opposite modulation from D2 /D3 R in CD (inhibitory) and D2 /D3 R in VS (stimulatory). In contrast, this modulation was not significant in cannabis abusers. Findings suggest that action speed requires balanced VS-inhibition from D2 /D3 R in CD and VS-facilitation from D2 /D3 R in VS.

SUBMITTER: Tomasi D

PROVIDER: S-EPMC6868956 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Balanced modulation of striatal activation from D2 /D3 receptors in caudate and ventral striatum: Disruption in cannabis abusers.

Tomasi Dardo D Wang Gene-Jack GJ Volkow Nora D ND

Human brain mapping 20150609 8

Proper communication between dorsal caudate (CD) and ventral striatum (VS) is likely to be crucial for on-time responses and its disruption might result in impulsivity. Here, we used functional magnetic resonance imaging (fMRI) with a sensorimotor reaction time task and positron emission tomography (PET) with [(11)C]raclopride in 14 healthy controls and 18 cannabis abusers to contrast the modulation of striatal fMRI responses by dopamine receptors (D2 /D3 R) in CD and VS. In controls, we show th ...[more]

PMID: 26058801

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Project description:ObjectiveDopamine is an endogenous neuromodulator in cortical circuits and the basal ganglia. In animal models of temporal lobe epilepsy (TLE), seizure threshold is modulated to some extent by dopamine, with D1-receptors having a pro- and D2-receptors an anticonvulsant effect. We aimed to extend our previously reported results on decreased D2/D3 receptor binding in the lateral epileptogenic temporal lobe and to correlate them with demographic and seizure variables to gain a more comprehensive understanding of the underlying involvement of the dopaminergic system in the epileptogenesis of TLE.MethodsTo quantify D2/D3 receptor binding, we studied 21 patients with TLE and hippocampal sclerosis (13 left- and eight right-sided) and 18 controls using PET with the high-affinity dopamine D2/D3-receptor ligand 18F-Fallypride to image striatal and extrastriatal binding. TLE was defined by interictal and ictal video-EEG, MRI and 18F-Fluorodeoxyglucose PET. Voxel-based statistical and regions-of-interest analyses were performed.Results18F-Fallypride binding potential was significantly reduced in the affected temporal lobe and bilateral putamen. A positive correlation between age at onset of epilepsy and [18F]FP BPnd (binding potential non-displaceable) in temporal regions on the epileptogenic side was found, as well as a negative correlation between epilepsy duration and [18F]FP BPnd in the temporal pole on the epileptogenic side and a positive correlation between the estimated number of lifetime GTCS and [18F]FP BPnd in the hippocampus on the epileptogenic side.SignificanceThe areas of reduced D2/D3 receptor availability correspond to "the irritative zone" surrounding the epileptogenic area. Moreover, reduced D2/D3 receptor availability was detectable in the basal ganglia, which are suspected to be involved in a control circuit for epileptic seizures. The correlational analysis additionally suggests that increased epilepsy duration leads to increasing impairment of the dopaminergic system.

Project description:Dopamine D2 and D3 autoreceptors are located on pre-synaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate-putamen and nucleus accumbens core and shell. The dopamine D2 agonists (-)-quinpirole hydrochloride and 5,6,7,8-Tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate-putamen and nucleus accumbens (core and shell) based on their EC(50) and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-Tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (+/-)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in caudate-putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate-putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.3 muM lowered the uptake rate in caudate-putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the pre-agonist dopamine release concentration. Finally, these results demonstrate a functional voltammetric assay that characterizes dopamine D2-like agonist as either D2- or D3-preferring agonists by taking advantage of the unique receptor density within the striatum.

Dataset Information

Balanced modulation of striatal activation from D2 /D3 receptors in caudate and ventral striatum: Disruption in cannabis abusers.

Publications

Balanced modulation of striatal activation from D2 /D3 receptors in caudate and ventral striatum: Disruption in cannabis abusers.

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