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Reproductive Medicine and Biology 2022In humans, catecholamines (including dopamine) have been identified in semen and fallopian tubes, while dopamine D2 receptors (D2DR) are found in the sperm midpiece...
PURPOSE
In humans, catecholamines (including dopamine) have been identified in semen and fallopian tubes, while dopamine D2 receptors (D2DR) are found in the sperm midpiece region. How dopamine dose affects human sperm function and whether dopamine treatment is useful in assisted reproductive technology is unclear.
METHODS
Sperm samples were obtained from patients with normal semen parameters undergoing fertility treatment. We investigated the effects of dopamine treatment on tyrosine phosphorylation and sperm motility. Sperm motility was analyzed using the computer-assisted sperm analysis (CASA) system.
RESULTS
This study revealed that various dopamine concentrations (0.1-100 μM) did not increase sperm tyrosine phosphorylation. Progressive motility increased substantially when treated with high concentrations of dopamine (10 and 100 μM) and was blocked by raclopride (a D2DR antagonist). After 24-h sperm culture, the addition of 10 μM dopamine significantly increased curvilinear velocity and amplitude of lateral head displacement, which are indicators of hyperactivation.
CONCLUSION
Dopamine did not affect tyrosine phosphorylation, but increased sperm motility. High concentrations of dopamine were more effective to accelerate sperm motility in cases where sperm motile capacity was low.
PubMed: 36310655
DOI: 10.1002/rmb2.12482 -
Journal of Neurophysiology Jul 2022Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is...
Abnormalities of auditory steady-state responses (ASSRs) and the effects of antipsychotic drugs on ASSRs have been investigated in patients with schizophrenia. It is presumed that drugs do not directly affect ASSRs because its abnormalities are associated with schizophrenia. Therefore, to investigate the direct effect of drugs on ASSRs, we established an ASSR evaluation system for common marmosets in a naïve state. Dopamine D1 receptor stimulation (SKF-81297, 2 mg/kg ip) significantly increased evoked power (EP) at 40 Hz. The phase locking factor (PLF) was increased significantly at 20, 30, 40, and 80 Hz. However, administration of a dopamine D1 receptor antagonist (SCH-39166, 0.3 mg/kg ip) resulted in a significant decrease in EP and PLF at 30 Hz. Dopamine D2 receptor stimulation (quinpirole, 1 mg/kg im) tended to increase EP and induced power (IP) at all frequencies, and a significant difference was observed at 30 Hz IP. There was no change in PLF at all frequencies. In addition, dopamine D2 receptor blockade (raclopride, 3 mg/kg ip) reduced EP and PLF at 30 Hz. Subcutaneous administration of the serotonin dopamine antagonist, risperidone (0.3 mg/kg), tended to increase IP and decrease PLF, but not significantly. Taken together, it is possible to compare the differences in the mode of action of drugs on ASSRs using naïve nonhuman primates. We measured the effects of dopamine receptor-related compounds on ASSR in marmosets. D1 receptor stimulation increased the phase locking factor (PLF) and evoked power (EP), and reduced the induced power (IP). D2 receptor stimulation increased the IP. D1 and D2 receptor blockers reduced the PLF and EP at 30 Hz. Different modes of action of various drugs related to psychiatric disorders were evaluated by administering antipsychotic drugs to naïve marmosets.
Topics: Acoustic Stimulation; Animals; Antipsychotic Agents; Callithrix; Dopamine Antagonists; Evoked Potentials, Auditory; Humans; Receptors, Dopamine D1; Receptors, Dopamine D2
PubMed: 35583977
DOI: 10.1152/jn.00147.2022 -
Frontiers in Pharmacology 2020Previous results indicate that dopamine (DA) release in the medial prefrontal cortex (mPFC) is modified by α adrenoceptor- but not D2 DA receptor- agonists and...
Previous results indicate that dopamine (DA) release in the medial prefrontal cortex (mPFC) is modified by α adrenoceptor- but not D2 DA receptor- agonists and antagonists, suggesting that DA measured by microdialysis in the mPFC originates from noradrenergic terminals. Accordingly, noradrenergic denervation was found to prevent α-receptor-mediated rise and fall of extracellular DA induced by atipamezole and clonidine, respectively, in the mPFC. The present study was aimed to determine whether DA released by dopaminergic terminals in the mPFC is not detected by microdialysis because is readily taken up by norepinephrine transporter (NET). Accordingly, the D2-antagonist raclopride increased the electrical activity of DA neurons in the ventral tegmental area (VTA) and enhanced extracellular DOPAC but failed to modify DA in the mPFC. However, in rats whose NET was either inactivated by nisoxetine or eliminated by noradrenergic denervation, raclopride still elevated extracellular DOPAC and activated dopaminergic activity, but also increased DA. Conversely, the D2-receptor agonist quinpirole reduced DOPAC but failed to modify DA in the mPFC in control rats. However, in rats whose NET was eliminated by noradrenergic denervation or inhibited by locally perfused nisoxetine, quinpirole maintained its ability to reduce DOPAC but acquired that of reducing DA. Moreover, raclopride and quinpirole, when locally perfused into the mPFC of rats subjected to noradrenergic denervation, were able to increase and decrease, respectively, extracellular DA levels, while being ineffective in control rats. Transient inactivation of noradrenergic neurons by clonidine infusion into the locus coeruleus, a condition where NET is preserved, was found to reduce extracellular NE and DA in the mPFC, whereas noradrenergic denervation, a condition where NET is eliminated, almost totally depleted extracellular NE but increased DA. Both transient inactivation and denervation of noradrenergic neurons were found to reduce the number of spontaneously active DA neurons and their bursting activity in the VTA. The results indicate that DA released in the mPFC by dopaminergic terminals is not detected by microdialysis unless DA clearance from extracellular space is inactivated. They support the hypothesis that noradrenergic terminals are the main source of DA measured by microdialysis in the mPFC during physiologically relevant activities.
PubMed: 33071798
DOI: 10.3389/fphar.2020.588160 -
Journal of Cerebral Blood Flow and... Jul 2022Compartmental modeling analysis of C-raclopride (RAC) PET data can be used to measure the dopaminergic response to intra-scan behavioral tasks. Bias in estimates of...
Compartmental modeling analysis of C-raclopride (RAC) PET data can be used to measure the dopaminergic response to intra-scan behavioral tasks. Bias in estimates of binding potential (BP) and its dynamic changes (ΔBP) can arise both when head motion is present and when the compartmental model used for parameter estimation deviates from the underlying biology. The purpose of this study was to characterize the effects of motion and model bias within the context of a behavioral task challenge, examining the impacts of different mitigation strategies. Seventy healthy adults were administered bolus plus constant infusion RAC during a simultaneous PET/magnetic resonance (MR) scan with a reward task experiment. BP and ΔBP were estimated using an extension of the Multilinear Reference Tissue Model (E-MRTM2) and a new method (DE-MRTM2) was proposed to selectively discount the contribution of the initial uptake period. Motion was effectively corrected with a standard frame-based approach, which performed equivalently to a more complex reconstruction-based approach. DE-MRTM2 produced estimates of ΔBP in putamen and nucleus accumbens that were significantly different from those estimated from E-MRTM2, while also decoupling ΔBP values from first-pass k' estimation and removing skew in the spatial bias distribution of parametric ΔBP estimates within the striatum.
Topics: Adult; Bias; Corpus Striatum; Dopamine; Humans; Positron-Emission Tomography; Raclopride
PubMed: 35118904
DOI: 10.1177/0271678X221078616 -
The Journal of Clinical Investigation Sep 2021BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity)...
BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.METHODSWe examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, 20 male; age 42.40 ± 12.22 years) and its relationship to drug reward. Rest-activity rhythms were assessed by 1-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride positron emission tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.RESULTSWe found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or so-called social jet lag, whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R, and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.CONCLUSIONThese findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability, and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov: NCT03190954.FUNDINGNational Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).
Topics: Actigraphy; Adult; Central Nervous System Stimulants; Circadian Rhythm; Corpus Striatum; Female; Humans; Male; Methylphenidate; Middle Aged; Motor Activity; Positron-Emission Tomography; Receptors, Dopamine D1; Receptors, Dopamine D2; Rest; Reward; Substance-Related Disorders; Young Adult
PubMed: 34264865
DOI: 10.1172/JCI149722 -
Frontiers in Aging Neuroscience 2022To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a...
To study the aging human brain requires significant resources and time. Thus, mice models of aging can provide insight into changes in brain biological functions at a fraction of the time when compared to humans. This study aims to explore changes in dopamine D and D receptor availability and of gray matter density in striatum during aging in mice and to evaluate whether longitudinal imaging in mice may serve as a model for normal brain aging to complement cross-sectional research in humans. Mice underwent repeated structural magnetic resonance imaging (sMRI), and [C]Raclopride and [C]SCH23390 positron emission tomography (PET) was performed on a subset of aging mice. PET and sMRI data were analyzed by binding potential (BP ), voxel- and tensor-based morphometry (VBM and TBM, respectively). Longitudinal PET revealed a significant reduction in striatal BP for D receptors over time, whereas no significant change was found for D receptors. sMRI indicated a significant increase in modulated gray matter density (mGMD) over time in striatum, with limited clusters showing decreased mGMD. Mouse [C]Raclopride data is compatible with previous reports in human cross-sectional studies, suggesting that a natural loss of dopaminergic D receptors in striatum can be assessed in mice, reflecting estimates from humans. No changes in D were found, which may be attributed to altered [C]SCH23390 kinetics in anesthetized mice, suggesting that this tracer is not yet able to replicate human findings. sMRI revealed a significant increase in mGMD. Although contrary to expectations, this increase in modulated GM density may be attributed to an age-related increase in non-neuronal cells.
PubMed: 35140600
DOI: 10.3389/fnagi.2022.795132 -
Frontiers in Behavioral Neuroscience 2021The current rodent study applied fast-scan cyclic voltammetry (FSCV), paired with a pharmacological approach, to measure the release of the catecholamines (CA) dopamine...
The current rodent study applied fast-scan cyclic voltammetry (FSCV), paired with a pharmacological approach, to measure the release of the catecholamines (CA) dopamine (DA) and norepinephrine (NE) in the basolateral amygdala (BLA) following locus coeruleus (LC) stimulation. The primary goal was to determine if exposure to either social (social defeat) or non-social (forced swim) stress altered LC-evoked catecholamine release dynamics in the BLA. We used idazoxan (α2 adrenergic receptor antagonist) and raclopride (D dopamine receptor antagonist) to confirm the presence of NE and DA, respectively, in the measured CA signal. In non-stressed rats, injection of idazoxan, but not raclopride, resulted in a significant increase in the detected CA signal, indicating the presence of NE but not DA. Following exposure to either stress paradigm, the measured CA release was significantly greater after injection of either drug, suggesting the presence of both NE and DA in the LC-induced CA signal after social or non-social stress. Furthermore, acute administration of alcohol significantly decreased the CA signal in stressed rats, while it did not have an effect in naïve animals. Together, these data reveal that, while LC stimulation primarily elicits NE release in the BLA of control animals, both social and non-social stress unmask a novel dopaminergic component of LC catecholamine signaling. Future studies will be needed to identify the specific neural mechanism(s) responsible for these plastic changes in LC-BLA catecholamine signaling and to assess the possible contribution of these changes to the maladaptive behavioral phenotypes that develop following exposure to these stressors.
PubMed: 33935662
DOI: 10.3389/fnbeh.2021.640651 -
Nicotine & Tobacco Research : Official... Oct 2022Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Tobacco smoking is a major public health burden. The first-line pharmacological treatment for tobacco smoking is nicotine replacement therapy (eg, the nicotine patch (NIC)). Nicotine acts on nicotinic-acetylcholine receptors on dopamine terminals to release dopamine in the ventral and dorsal striatum encoding reward and habit formation, respectively.
AIMS AND METHODS
To better understand treatment efficacy, a naturalistic experimental design combined with a kinetic model designed to characterize smoking-induced dopamine release in vivo was used. Thirty-five tobacco smokers (16 female) wore a NIC (21 mg, daily) for 1-week and a placebo patch (PBO) for 1-week in a randomized, counter-balanced order. Following 1-week under NIC and then overnight abstinence, smokers participated in a 90-minute [11C]raclopride positron emission tomography scan and smoked a cigarette while in the scanner. Identical procedures were followed for the PBO scan. A time-varying kinetic model was used at the voxel level to model transient dopamine release peaking instantaneously at the start of the stimulus and decaying exponentially. Magnitude and spatial extent of dopamine release were estimated. Smokers were subcategorized by nicotine dependence level and nicotine metabolism rate.
RESULTS
Dopamine release magnitude was enhanced by NIC in ventral striatum and diminished by NIC in dorsal striatum. More-dependent smokers activated more voxels than the less-dependent smokers under both conditions. Under PBO, fast metabolizers activated more voxels in ventral striatum and fewer voxels in dorsal striatum compared to slow metabolizers.
CONCLUSIONS
These findings demonstrate that the model captured a pattern of transient dopamine responses to cigarette smoking which may be different across smoker subgroup categorizations.
IMPLICATIONS
This is the first study to show that NIC alters highly localized patterns of cigarette smoking-induced dopamine release and that levels of nicotine dependence and nicotine clearance rate contribute to these alterations. This current work included a homogeneous subject sample with regards to demographic and smoking variables, as well as a highly sensitive model capable of detecting significant acute dopamine transients. The findings of this study add support to the recent identification of biomarkers for predicting the effect of nicotine replacement therapies on dopamine function which could help refine clinical practice for smoking cessation.
Topics: Female; Humans; Biomarkers; Cigarette Smoking; Dopamine; Nicotine; Raclopride; Receptors, Nicotinic; Smoking Cessation; Nicotiana; Tobacco Use Cessation Devices; Tobacco Use Disorder
PubMed: 35100429
DOI: 10.1093/ntr/ntac026 -
Journal of Physiology and Pharmacology... Jun 2022Dopamine D1-like and D2-like receptors are expressed in the pulmonary arteries, however there is a little information about their effect on vascular tone in pulmonary...
Dopamine D1-like and D2-like receptors are expressed in the pulmonary arteries, however there is a little information about their effect on vascular tone in pulmonary circulation, even the vascular effect of activation of the dopamine D and D subtypes in physiological and pathological conditions such as pulmonary hypertension is unknown. The objective of this study was to evaluate the vascular response of trunk pulmonary artery rings from saline and monocrotaline-treated rats in the presence of selective dopamine receptor agonists. In trunk pulmonary artery rings with intact and denuded endothelium, cumulative concentration-response curves were performed for phenylephrine, acetylcholine, and dopamine receptor agonists (apomorphine-D2-like, SKF38393-D, quinpirole-D/D, 7-OH-DPATD, and PD168077-D) alone and in the presence of corresponding selective dopamine receptor antagonists (SCH23390-D, raclopride-D/D, U99194 maleate-D, and L-745,870-D). Contractile and relaxant effects generated during the activation with phenylephrine and acetylcholine, respectively, were significantly reduced in intact and denuded endothelium trunk pulmonary artery rings from monocrotaline rats in comparison with control rats. All dopamine receptor agonists, except the 7-OH-DPAT, produced significant vascular relaxation in intact trunk pulmonary artery rings precontracted with phenylephrine in both experimental groups. Also, the vascular relaxation of SKF38393, and particularly apomorphine and PD168077 was significant in denuded endothelium trunk pulmonary artery rings from control and monocrotaline groups. Furthermore, the vasorelaxation induced by these dopamine agonists was significantly reduced in pulmonary preparations from monocrotaline-treated rats in comparison to that recorded in preparations from control rats. The effect of dopamine receptor agonists decreased significantly in the presence of the corresponding antagonist in both experimental groups. The results support that dopamine D receptor agonist induces significant vascular relaxation, whereas dopamine D receptor agonist induces vasoconstriction in intact and denuded endothelium trunk pulmonary artery rings in control and monocrotaline-induced pulmonary arterial hypertension rats.
Topics: Rats; Animals; Dopamine Agonists; Dopamine; Apomorphine; Receptors, Dopamine D2; Pulmonary Artery; Monocrotaline; 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Acetylcholine; Phenylephrine
PubMed: 36515630
DOI: 10.26402/jpp.2022.3.15 -
Schizophrenia Bulletin Aug 2021Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine...
BACKGROUND
Between unaffected mental health and diagnosable psychiatric disorders, there is a vast continuum of functioning. The hypothesized link between striatal dopamine signaling and psychosis has guided a prolific body of research. However, it has been understudied in the context of multiple interacting factors, subclinical phenotypes, and pre-postsynaptic dynamics.
METHOD
This work investigated psychotic-like experiences and D2/3 dopamine postsynaptic receptor availability in the dorsal striatum, quantified by in vivo [11C]-raclopride positron emission tomography, in a sample of 24 healthy male individuals. Additional mediation and moderation effects with childhood trauma and key dopamine-regulating genes were examined.
RESULTS
An inverse relationship between nondisplaceable binding potential and subclinical symptoms was identified. D2/3 receptor availability in the left putamen fully mediated the association between traumatic childhood experiences and odd beliefs, that is, inclinations to see meaning in randomness and unfounded interpretations. Moreover, the effect of early adversity was moderated by a DRD2 functional variant (rs1076560). The results link environmental and neurobiological influences in the striatum to the origination of psychosis spectrum symptomology, consistent with the social defeat and diathesis-stress models.
CONCLUSIONS
Adversity exposure may affect the dopamine system as in association with biases in probabilistic reasoning, attributional style, and salience processing. The inverse relationship between D2/3 availability and symptomology may be explained by endogenous dopamine occupying the receptor, postsynaptic compensatory mechanisms, and/or altered receptor sensitivity. This may also reflect a cognitively stabilizing mechanism in non-help-seeking individuals. Future research should comprehensively characterize molecular parameters of dopamine neurotransmission along the psychosis spectrum and according to subtype profiling.
Topics: Adult; Adult Survivors of Child Adverse Events; Adverse Childhood Experiences; Dopamine; Dopamine D2 Receptor Antagonists; Female; Humans; Male; Neostriatum; Positron-Emission Tomography; Psychological Trauma; Psychotic Disorders; Raclopride; Receptors, Dopamine D2; Receptors, Dopamine D3
PubMed: 33876249
DOI: 10.1093/schbul/sbab034