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Social Cognitive and Affective... May 2022Mothers are highly responsive to their offspring. In non-human mammals, mothers secrete dopamine in the nucleus accumbens (NAcc) in response to their pups. Yet, it is...
Mothers are highly responsive to their offspring. In non-human mammals, mothers secrete dopamine in the nucleus accumbens (NAcc) in response to their pups. Yet, it is still unknown which aspect of the offspring behavior elicits dopaminergic responses in mothers. Here, we tested whether infants' affective signals elicit dopaminergic responses in the NAcc of human mothers. First, we conducted a behavioral analysis on videos of infants' free play and quantified the affective signals infants spontaneously communicated. Then, we presented the same videos to mothers during a magnetic resonance-positron emission tomography scan. We traced the binding of [11C]raclopride to free D2/3-type receptors to assess maternal dopaminergic responses during the infant videos. When mothers observed videos with many infant signals during the scan, they had less [11C]raclopride binding in the right NAcc. Less [11C]raclopride binding indicates that less D2/3 receptors were free, possibly due to increased endogenous dopamine responses to infants' affective signals. We conclude that NAcc D2/3 receptors are involved in maternal responsiveness to affective signals of human infants. D2/3 receptors have been associated with maternal responsiveness in nonhuman animals. This evidence supports a similar mechanism in humans and specifies infant-behaviors that activate the maternal dopaminergic system, with implications for social neuroscience, development and psychopathology.
Topics: Animals; Dopamine; Humans; Mammals; Nucleus Accumbens; Positron-Emission Tomography; Raclopride; Receptors, Dopamine D2
PubMed: 34750627
DOI: 10.1093/scan/nsab116 -
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 -
The Journal of Comparative Neurology Jun 2021Adult neurogenesis in rodents is modulated by dopaminergic signaling and inhibited by cocaine. However, the sex-specific role of dopamine D1 and D2 receptors (D1R, D2R)...
Adult neurogenesis in rodents is modulated by dopaminergic signaling and inhibited by cocaine. However, the sex-specific role of dopamine D1 and D2 receptors (D1R, D2R) in the deleterious effect of cocaine on adult neurogenesis has not been described yet. Here, we explored sex differences in (a) cell proliferation (5'-bromo-2'-deoxyuridine [BrdU]), (b) neural precursor (nestin), (c) neuronal phenotype (BrdU/β3-tubulin), and (d) neuronal maturity (NeuN) in the subventricular zone (SVZ) of the lateral ventricles and striatum of mice with genetic deletion (D1 , D2 ) or pharmacological blockage (SCH23390: 0.1 mg/kg/day/5 days; Raclopride: 0.3 mg/kg/day/5 days) of D1R and D2R, and treated (10 mg/kg/day/5 days) and then challenged (5 mg/kg, 48 hr later) with cocaine. Results indicated that hyperactivity responses to cocaine were absent in D1 mice and reduced in SCH23390-treated mice. Activity responses to cocaine were reduced in D2 males, but absent in D2 females and increased in Raclopride-treated females. D1R deletion blocked the deleterious effect of cocaine on SVZ cell proliferation in males. Cocaine-exposed D1 males also had reduced neuronal phenotype of SVZ newborn cells and increased striatal neuronal maturity. D2 mice had lower proliferative and neural precursor responses. Cocaine in D2 females or coadministered with Raclopride in wild-type females improved SVZ cell proliferation, an effect that positively correlated with plasma brain-derived neurotrophic factor (BDNF) concentrations. In conclusion, the sex-specific D1R and D2R signaling on SVZ cell proliferation, neural progenitor and neuronal maturity is differentially perturbed by cocaine, and BDNF may be required to link D2R to neuroplasticity in cocaine addiction in females.
Topics: Animals; Cocaine; Cocaine-Related Disorders; Dopamine Uptake Inhibitors; Female; Lateral Ventricles; Male; Mice; Mice, Knockout; Neurogenesis; Neurons; Receptors, Dopamine D1; Receptors, Dopamine D2; Sex Characteristics
PubMed: 33047300
DOI: 10.1002/cne.25052 -
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 -
JCI Insight May 2021Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors...
Bariatric surgery is the most effective method for weight loss in morbid obesity. There is significant individual variability in the weight loss outcomes, yet factors leading to postoperative weight loss or weight regain remain elusive. Alterations in the μ-opioid receptor (MOR) and dopamine D2 receptor (D2R) systems are associated with obesity and appetite control, and the magnitude of initial brain receptor system perturbation may predict long-term surgical weight loss outcomes. We tested this hypothesis by studying 19 morbidly obese women (mean BMI 40) scheduled to undergo bariatric surgery. We measured their preoperative MOR and D2R availabilities using positron emission tomography with [11C]carfentanil and [11C]raclopride, respectively, and then assessed their weight development association with regional MOR and D2R availabilities at 24-month follow-up. MOR availability in the amygdala consistently predicted weight development throughout the follow-up period, but no associations were found for D2R. This is the first study to our knowledge to demonstrate that neuroreceptor markers prior to bariatric surgery are associated with postoperative weight development. Postoperative weight regain may derive from dysfunction in the opioid system, and weight loss outcomes after bariatric surgery may be partially predicted based on preoperative brain receptor availability, opening up new potential for treatment possibilities.
Topics: Adult; Bariatric Surgery; Brain; Female; Humans; Middle Aged; Neuroimaging; Obesity, Morbid; Positron-Emission Tomography; Preoperative Period; Receptors, Dopamine D2; Receptors, Opioid, mu; Weight Gain; Weight Loss
PubMed: 33848266
DOI: 10.1172/jci.insight.147820 -
Human Brain Mapping Aug 2021Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for...
Although striatal dopamine neurotransmission is believed to be functionally linked to the formation of the corticostriatal network, there has been little evidence for this regulatory process in the human brain and its disruptions in neuropsychiatric disorders. Here, we aimed to investigate associations of striatal dopamine transporter (DAT) and D receptor availabilities with gray matter (GM) volumes in healthy humans. Positron emission tomography images of D receptor (n = 34) and DAT (n = 17) captured with the specific radioligands [ C]raclopride and [ F]FE-PE2I, respectively, were acquired along with T1-weighted magnetic resonance imaging data in our previous studies, and were re-analyzed in this work. We quantified the binding potentials (BP ) of these radioligands in the limbic, executive, and sensorimotor functional subregions of the striatum. Correlations between the radioligand BP and regional GM volume were then examined by voxel-based morphometry. In line with the functional and anatomical connectivity, [ C]raclopride BP in the limbic striatum was positively correlated with volumes of the uncal/parahippocampal gyrus and adjacent temporal areas. Similarly, we found positive correlations between the BP of this radioligand in the executive striatum and volumes of the prefrontal cortices and their adjacent areas as well as between the BP in the sensorimotor striatum and volumes of the somatosensory and supplementary motor areas. By contrast, no significant correlation was found between [ F]FE-PE2I BP and regional GM volumes. Our results suggest unique structural and functional corticostriatal associations involving D receptor in healthy humans, which might be partially independent of the nigrostriatal pathway reflected by striatal DAT.
Topics: Adult; Dopamine Plasma Membrane Transport Proteins; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Neostriatum; Positron-Emission Tomography; Prefrontal Cortex; Radiopharmaceuticals; Receptors, Dopamine D2; Ventral Striatum; Young Adult
PubMed: 34014611
DOI: 10.1002/hbm.25538