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Brain Research Dec 2022Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male...
Here we studied spinal neurotransmitter mechanisms involved in the reduction of mechanical hypersensitivity by inhibition of the amygdaloid central nucleus (CeA) in male and female rats with spared nerve injury (SNI) model of neuropathy. SNI induced mechanical hypersensitivity that was stronger in females. Reversible blocking of the CeA with muscimol (GABA receptor agonist) induced a reduction of mechanical hypersensitivity that did not differ between males and females. Following spinal co-administration of atipamezole (α-adrenoceptor antagonist), the reduction of mechanical hypersensitivity by CeA muscimol was attenuated more in males than females. In contrast, following spinal co-administration of raclopride (dopamine D2 receptor antagonist) the reduction of hypersensitivity by CeA muscimol was attenuated more in females than males. The reduction of mechanical hypersensitivity by CeA muscimol was equally attenuated in males and females by spinal co-administration of WAY-100635 (5-HT receptor antagonist) or bicuculline (GABA receptor antagonist). The CeA muscimol induced attenuation of ongoing pain-like behavior (conditioned place preference test) that was reversed by spinal co-administration of atipamezole in both sexes. The results support the hypothesis that CeA contributes to mechanical hypersensitivity and ongoing pain-like behavior in SNI males and females. Disinhibition of descending controls acting on spinal α-adrenoceptors, 5-HT, dopamine D2 and GABA receptors provides a plausible explanation for the reduction of mechanical hypersensitivity by CeA block in SNI. The involvement of spinal dopamine D2 receptors and α-adrenoceptors in the CeA muscimol-induced reduction of mechanical hypersensitivity is sexually dimorphic, unlike that of spinal α-adrenoceptors in the reduction of ongoing neuropathic pain.
Topics: Female; Rats; Male; Animals; Muscimol; Receptors, GABA-A; Neuralgia; Amygdala; Receptors, Neurotransmitter; GABA-A Receptor Antagonists; Receptors, Adrenergic
PubMed: 36265669
DOI: 10.1016/j.brainres.2022.148128 -
Biological & Pharmaceutical Bulletin 2021The dopamine system plays an important role in regulating many brain functions, including the motor function. The blockade of dopamine receptors results in a serious...
The dopamine system plays an important role in regulating many brain functions, including the motor function. The blockade of dopamine receptors results in a serious motor dysfunction, such as catalepsy and Parkinsonism. However, the neuronal mechanism underlying the drug-induced motor dysfunction is not well understood. Here, we examine brain-wide activation patterns in Fos-enhanced green fluorescent protein reporter mice that exhibit cataleptic behavior induced by SCH39166, a dopamine D1-like receptor antagonist, and raclopride, a dopamine D2-like receptor antagonist. Support vector classifications showed that the orbital cortex (ORB) and striatum including the caudoputamen (CP) and nucleus accumbens (ACB), prominently contribute to the discrimination between brains of the vehicle-treated and both SCH39166- and raclopride-treated mice. Interregional correlations indicated that the increased functional connectivity of functional networks, including the ORB, CP, and ACB, is the common mechanism underlying SCH39166- and raclopride-induced cataleptic behavior. Moreover, the distinct mechanisms in the SCH39166- and raclopride-induced cataleptic behaviors are the decreased functional connectivity between three areas above and the cortical amygdala, and between three areas above and the anterior cingulate cortex, respectively. Thus, the alterations of functional connectivity in diverse brain regions, including the ORB, provide new insights on the mechanism underlying drug-induced movement disorders.
Topics: Animals; Benzazepines; Catalepsy; Corpus Striatum; Dopamine Antagonists; Mice, Inbred C57BL; Mice, Transgenic; Prefrontal Cortex; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2; Mice
PubMed: 33642553
DOI: 10.1248/bpb.b20-01006 -
Journal of Magnetic Resonance Imaging :... Nov 2021Recent studies have established a clear topographical and functional organization of projections to and from complex subdivisions of the striatum. Manual segmentation of...
BACKGROUND
Recent studies have established a clear topographical and functional organization of projections to and from complex subdivisions of the striatum. Manual segmentation of these functional subdivisions is labor-intensive and time-consuming, and automated methods are not as reliable as manual segmentation.
PURPOSE
To utilize multitask learning (MTL) as a method to segment subregions of the striatum consisting of pre-commissural putamen (prePU), pre-commissural caudate (preCA), post-commissural putamen (postPU), post-commissural caudate (postCA), and ventral striatum (VST).
STUDY TYPE
Retrospective.
POPULATION
Eighty-seven total data sets from patients with schizophrenia and matched controls.
FIELD STRENGTH/SEQUENCE
1.5 T and 3.0 T, T -weighted (SPGR SENSE, 3D BRAVO).
ASSESSMENT
MTL-generated segmentations were compared to the Imperial College London Clinical Imaging Center (CIC) atlas. Dice similarity coefficient (DSC) was used to compare the automated methods to manual segmentations. Positron emission tomography (PET) imaging: 60 minutes of emission data were acquired using [ C]raclopride. Data were reconstructed by filtered back projection (FBP) with computed tomography (CT) used for attenuation correction. Binding potential values, BP , and region of interest (ROI) time series and whole-brain connectivity using functional magnetic resonance imaging (fMRI) images were compared between manual and both automated segmentations.
STATISTICAL TESTS
Pearson correlation and paired t-test.
RESULTS
MTL-generated segmentations showed excellent spatial agreement with manual (DSC ≥0.72 across all striatal subregions). BP values from MTL-generated segmentations were shown to correlate well with manual segmentations with R ≥ 0.91 in all caudate and putamen subregions, and R = 0.69 in VST. Mean Pearson correlation coefficients of the fMRI data between MTL-generated and manual segmentations were also high in time series (≥0.86) and whole-brain connectivity (≥0.89) across all subregions.
DATA CONCLUSION
Across both PET and fMRI task-based assessments, results from MTL-generated segmentations more closely corresponded to results from manually drawn ROIs than CIC-generated segmentations did. Therefore, the proposed MTL approach is a fast and reliable method for three-dimensional striatal subregion segmentation with results comparable to manually segmented ROIs.
LEVEL OF EVIDENCE
2 TECHNICAL EFFICACY STAGE: 1.
Topics: Brain; Corpus Striatum; Humans; Magnetic Resonance Imaging; Positron-Emission Tomography; Retrospective Studies
PubMed: 33970510
DOI: 10.1002/jmri.27682 -
Journal of Cerebral Blood Flow and... Jul 2023The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3...
Striatal dopamine transporter and receptor availability correlate with relative cerebral blood flow measured with [C]PE2I, [F]FE-PE2I and [C]raclopride PET in healthy individuals.
The aim of this retrospective study was to investigate relationships between relative cerebral blood flow and striatal dopamine transporter and dopamine D2/3 availability in healthy subjects. The data comprised dynamic PET scans with two dopamine transporter tracers [C]PE2I (n = 20) and [F]FE-PE2I (n = 20) and the D2/3 tracer [C]raclopride (n = 18). Subjects with a [C]PE2I scan also underwent a dynamic scan with the serotonin transporter tracer [C]DASB. Binding potential (BP) and relative tracer delivery (R) values were calculated on regional and voxel-level. Striatal R and BP values were correlated, using either an MRI-based volume of interest (VOI) or an isocontour VOI based on the parametric BP image. An inter-tracer comparison between [C]PE2I BP and [C]DASB R was done on a VOI-level and simulations were performed to investigate whether the constraints of the modeling could cause correlation of the parameters. A positive association was found between BP and R for all three dopamine tracers. A similar correlation was found for the inter-tracer correlation between [C]PE2I BP and [C]DASB R. Simulations showed that this relationship was not caused by cross-correlation between parameters in the kinetic model. In conclusion, these results suggest an association between resting-state striatal dopamine function and relative blood flow in healthy subjects.
Topics: Humans; Raclopride; Dopamine; Dopamine Plasma Membrane Transport Proteins; Retrospective Studies; Positron-Emission Tomography; Cerebrovascular Circulation
PubMed: 36912083
DOI: 10.1177/0271678X231160881 -
Molecular Psychiatry Feb 2022Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized....
Sex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of "drug effects" and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).
Topics: Attention Deficit Disorder with Hyperactivity; Central Nervous System Stimulants; Corpus Striatum; Dopamine; Female; Humans; Male; Methylphenidate; Raclopride; Sex Characteristics; Ventral Striatum
PubMed: 34707237
DOI: 10.1038/s41380-021-01294-9 -
Psychiatry and Clinical Neurosciences Apr 2020The aim of the study was to test: (i) if D /D binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in...
[ C]raclopride positron emission tomography study of dopamine-D receptor binding in patients with severe major depressive episodes before and after electroconvulsive therapy and compared to control subjects.
AIM
The aim of the study was to test: (i) if D /D binding in three functional subsections of striatum is different in patients with severe major depressive episodes than in controls; and (ii) if this difference is normalized after electroconvulsive therapy (ECT).
METHODS
Nine inpatients were examined with positron emission tomography (PET) and the radioligand [ C]raclopride before and after an average of 8.4 ECT sessions. Treatment response was assessed using the Montgomery-Åsberg Depression Rating Scale. Nine age- and sex-matched controls were examined twice with PET and [ C]raclopride.
RESULTS
[ C]raclopride binding was significantly lower in all three subsections of striatum in patients compared to controls (Cohen's d , 1.14-1.68; P = 0.003-0.027). Montgomery-Åsberg Depression Ratings decreased significantly after ECT (P < 0.001; Cohen's d , 2.9). ECT had no statistically significant effect on [ C]raclopride binding, although post-ECT binding estimates were more similar to those obtained in controls in all subsections of striatum.
CONCLUSION
Using PET and [ C]raclopride, we found support for the notion that severe major depressive episodes are associated with significantly lower dopamine D /D binding in all three subsections of striatum compared to controls. We noted no significant effect on D /D binding in the patient group after response to ECT.
Topics: Adult; Aged; Brain Mapping; Carbon Radioisotopes; Corpus Striatum; Depressive Disorder, Major; Dopamine; Dopamine Antagonists; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Positron-Emission Tomography; Protein Binding; Raclopride; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 31943514
DOI: 10.1111/pcn.12980 -
EJNMMI Physics Feb 2021The Siemens high-resolution research tomograph (HRRT - a dedicated brain PET scanner) is to this day one of the highest resolution PET scanners; thus, it can serve as...
BACKGROUND
The Siemens high-resolution research tomograph (HRRT - a dedicated brain PET scanner) is to this day one of the highest resolution PET scanners; thus, it can serve as useful benchmark when evaluating performance of newer scanners. Here, we report results from a cross-validation study between the HRRT and the whole-body GE SIGNA PET/MR focusing on brain imaging. Phantom data were acquired to determine recovery coefficients (RCs), % background variability (%BG), and image voxel noise (%). Cross-validation studies were performed with six healthy volunteers using [C]DTBZ, [C]raclopride, and [F]FDG. Line profiles, regional time-activity curves, regional non-displaceable binding potentials (BP) for [C]DTBZ and [C]raclopride scans, and radioactivity ratios for [F]FDG scans were calculated and compared between the HRRT and the SIGNA PET/MR.
RESULTS
Phantom data showed that the PET/MR images reconstructed with an ordered subset expectation maximization (OSEM) algorithm with time-of-flight (TOF) and TOF + point spread function (PSF) + filter revealed similar RCs for the hot spheres compared to those obtained on the HRRT reconstructed with an ordinary Poisson-OSEM algorithm with PSF and PSF + filter. The PET/MR TOF + PSF reconstruction revealed the highest RCs for all hot spheres. Image voxel noise of the PET/MR system was significantly lower. Line profiles revealed excellent spatial agreement between the two systems. BP values revealed variability of less than 10% for the [C]DTBZ scans and 19% for [C]raclopride (based on one subject only). Mean [F]FDG ratios to pons showed less than 12% differences.
CONCLUSIONS
These results demonstrated comparable performances of the two systems in terms of RCs with lower voxel-level noise (%) present in the PET/MR system. Comparison of in vivo human data confirmed the comparability of the two systems. The whole-body GE SIGNA PET/MR system is well suited for high-resolution brain imaging as no significant performance degradation was found compared to that of the reference standard HRRT.
PubMed: 33635449
DOI: 10.1186/s40658-020-00349-0 -
Biomedicines May 2022Food odour is a potent stimulus of food intake. Odour coding in the brain occurs in synergy or competition with other sensory information and internal signals. For...
Food odour is a potent stimulus of food intake. Odour coding in the brain occurs in synergy or competition with other sensory information and internal signals. For eliciting feeding behaviour, food odour coding has to gain signification through enrichment with additional labelling in the brain. Since the ventral striatum, at the crossroads of olfactory and reward pathways, receives a rich dopaminergic innervation, we hypothesized that dopamine plays a role in food odour information processing in the ventral striatum. Using single neurones recordings in anesthetised rats, we show that some ventral striatum neurones respond to food odour. This neuronal network displays a variety of responses (excitation, inhibition, rhythmic activity in phase with respiration). The localization of recorded neurones in a 3-dimensional brain model suggests the spatial segregation of this food-odour responsive population. Using local field potentials recordings, we found that the neural population response to food odour was characterized by an increase of power in the beta-band frequency. This response was modulated by dopamine, as evidenced by its depression following administration of the dopaminergic D1 and D2 antagonists SCH23390 and raclopride. Our results suggest that dopamine improves food odour processing in the ventral striatum.
PubMed: 35625863
DOI: 10.3390/biomedicines10051126 -
Communications Biology Sep 2022Eye-blink rate has been proposed as a biomarker of the brain dopamine system, however, findings have not been consistent. This study assessed the relationship between...
Eye-blink rate has been proposed as a biomarker of the brain dopamine system, however, findings have not been consistent. This study assessed the relationship between blink rates, measured after oral placebo) (PL) and after a challenge with oral methylphenidate (MP; 60 mg) and striatal D1 receptor (D1R) (measured at baseline) and D2 receptor (D2R) availability (measured after PL and after MP) in healthy participants. PET measures of baseline D1R ([C]NNC112) (BL-D1R) and D2R availability ([C]raclopride) after PL (PL-D2R) and after MP (MP-D2R) were quantified in the striatum as non-displaceable binding potential. MP reduced the number of blinks and increased the time participants kept their eyes open. Correlations with dopamine receptors were only significant for the eye blink measures obtained after MP; being positive for BL-D1R in putamen and MP-D2R in caudate (PL-D2R were not significant). MP-induced changes in blink rates (PL minus MP) were negatively correlated with BL-D1R in caudate and putamen. Our findings suggest that eye blink measures obtained while stressing the dopamine system might provide a more sensitive behavioral biomarker of striatal D1R or D2R in healthy volunteers than that obtained at baseline or after placebo.
Topics: Corpus Striatum; Dopamine; Humans; Methylphenidate; Raclopride; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 36163254
DOI: 10.1038/s42003-022-03979-5 -
Cerebral Cortex (New York, N.Y. : 1991) Jun 2023In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system...
In rodents and nonhuman primates, sex hormones are powerful modulators of dopamine (DA) neurotransmission. Yet less is known about hormonal regulation of the DA system in the human brain. Using positron emission tomography (PET), we address this gap by comparing hormonal contraceptive users and nonusers across multiple aspects of DA function: DA synthesis capacity via the PET radioligand 6-[18F]fluoro-m-tyrosine ([18F]FMT), baseline D2/3 receptor binding potential using [11C]raclopride, and DA release using methylphenidate-paired [11C]raclopride. Participants consisted of 36 healthy women (n = 15 hormonal contraceptive users; n = 21 naturally cycling/non users of hormonal contraception), and men (n = 20) as a comparison group. A behavioral index of cognitive flexibility was assessed prior to PET imaging. Hormonal contraceptive users exhibited greater DA synthesis capacity than NC participants, particularly in dorsal caudate, and greater cognitive flexibility. Furthermore, across individuals, the magnitude of striatal DA synthesis capacity was associated with cognitive flexibility. No group differences were observed in D2/3 receptor binding or DA release. Analyses by sex alone may obscure underlying differences in DA synthesis tied to women's hormone status. Hormonal contraception (in the form of pill, shot, implant, ring, or intrauterine device) is used by ~400 million women worldwide, yet few studies have examined whether chronic hormonal manipulations impact basic properties of the DA system. Findings from this study begin to address this critical gap in women's health.
Topics: Male; Animals; Humans; Female; Raclopride; Dopamine; Contraceptive Agents; Positron-Emission Tomography; Receptors, Dopamine D2; Cognition
PubMed: 37160338
DOI: 10.1093/cercor/bhad134