scholarly journals Brain dopamine response in human opioid addiction

2008 ◽  
Vol 193 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Mark R.C. Daglish ◽  
Tim M. Williams ◽  
Sue J. Wilson ◽  
Lindsay G. Taylor ◽  
Chin B. Eap ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Subjective Experience ◽  
Methadone Maintenance ◽  
Random Order ◽  
Rat Striatum ◽  
Dopamine System ◽  
Double Blind ◽  
Brain Scans ◽  
Positron Emission

BackgroundDrugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugsAimsWe tested whether opioids provoke dopamine release and its relationship to the subjective experienceMethodIn two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [11C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order designResultsBoth opioids produced marked subjective and physiological effects, but no measurable change in [11C]-raclopride bindingConclusionsThe absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts

scholarly journals Levodopa effects on [11C]raclopride binding in the resting human brain

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 23 ◽  
Author(s):  
Kevin J. Black ◽  
Marilyn L. Piccirillo ◽  
Jonathan M. Koller ◽  
Tiffany Hseih ◽  
Lei Wang ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Random Order ◽  
Binding Potential ◽  
Separate Analysis ◽  
Double Blind ◽  
Positron Emission ◽  
Midbrain Region ◽  
And Control ◽  
Double Blind Crossover Study ◽  
Da Release

Rationale: Synaptic dopamine (DA) release induced by amphetamine or other experimental manipulations can displace [11C]raclopride (RAC*) from dopamine D2-like receptors. We hypothesized that exogenous levodopa might increase dopamine release at striatal synapses under some conditions but not others, allowing a more naturalistic assessment of presynaptic dopaminergic function. Presynaptic dopaminergic abnormalities have been reported in Tourette syndrome (TS).Objective: Test whether levodopa induces measurable synaptic DA release in healthy people at rest, and gather pilot data in TS.Methods: This double-blind crossover study used RAC* and positron emission tomography (PET) to measure synaptic dopamine release 4 times in each of 10 carbidopa-pretreated, neuroleptic-naïve adults: before and during an infusion of levodopa on one day and placebo on another (in random order). Five subjects had TS and 5 were matched controls. RAC* binding potential (BPND) was quantified in predefined anatomical volumes of interest (VOIs). A separate analysis compared BPND voxel by voxel over the entire brain.Results: DA release declined between the first and second scan of each day (p=0.012), including on the placebo day. Levodopa did not significantly reduce striatal RAC* binding and striatal binding did not differ significantly between TS and control groups. However, levodopa’s effect on DA release differed significantly in a right midbrain region (p=0.002, corrected), where levodopa displaced RAC* by 59% in control subjects but increased BPND by 74% in TS subjects.Discussion: Decreased DA release on the second scan of the day is consistent with the few previous studies with a similar design, and may indicate habituation to study procedures. We hypothesize that mesostriatal DA neurons fire relatively little while subjects rest, possibly explaining the non-significant effect of levodopa on striatal RAC* binding. The modest sample size argues for caution in interpreting the group difference in midbrain DA release with levodopa.

scholarly journals Dopamine manipulations drive changes in information sampling in healthy volunteers

2019 ◽  
Vol 33 (6) ◽  
pp. 670-677
Author(s):  
Raquel Vicario-Feliciano ◽  
Rebekah L Wigton ◽  
Thomas P White ◽  
Sukhi S Shergill ◽  
Bruno B Averbeck
Keyword(s):  
Cognitive Process ◽  
Dopamine Release ◽  
Receptor Activation ◽  
Choice Task ◽  
Double Blind ◽  
Information Sampling ◽  
Dopamine Signaling ◽  
Beads Task ◽  
Choice Tasks

Background: Information sampling is the cognitive process of accumulating information before committing to a decision. Patients across numerous disorders show decreased information sampling relative to controls. Aims: Here, we used the Beads and the Best Choice Tasks to study the role of dopamine signaling in information sampling. Methods: Participants were given placebo, amisulpride, or ropinirole in each session, in a double-blind cross-over design. Results: We found that ropinirole (agonist) increased the number of beads drawn in the Beads Task specifically when participants faced a loss, and decreased the rank of the chosen option in the Best Choice Task. Conclusions: These effects are likely driven by a combination of effects at presynaptic D2 receptors, which affect dopamine release, and post-synaptic D2 receptors. Increased D2 relative to D1 receptor activation in the striatum leads to increased sampling in the loss condition in the Beads Task. It also leads to choice of a poorer ranked option in the Best Choice Task. Decreased D2 relative to D1 receptor activation leads to decreased sampling in the Beads Task in the loss condition.

scholarly journals Diuretic effect of hypoxia, hypocapnia, and hyperpnea in humans: relation to hormones and O2 chemosensitivity

2000 ◽  
Vol 88 (2) ◽  
pp. 599-610 ◽  
Author(s):  
Wulf Hildebrandt ◽  
Andy Ottenbacher ◽  
Markus Schuster ◽  
Erik R. Swenson ◽  
Peter Bärtsch
Keyword(s):  
Random Order ◽  
Systemic Blood Pressure ◽  
Urine Flow ◽  
Hypoxic Ventilatory Response ◽  
Venous Compliance ◽  
Double Blind ◽  
Diuretic Response ◽  
Male Subjects ◽  
Sodium Clearance

We studied the contributions of hypoxemia, hypocapnia, and hyperpnea to the acute hypoxic diuretic response (HDR) in humans and evaluated the role of peripheral O2 chemosensitivity and renal hormones in HDR. Thirteen healthy male subjects (age 19–38 yr) were examined after sodium equilibration (intake: 120 mmol/day) during 90 min of normoxia (NO), poikilocapnic hypoxia (PH), and isocapnic hypoxia (IH) ( days 1–3, random order, double blind), as well as normoxic voluntary hyperpnea (HP; day 4), matching ventilation during IH. O2 saturation during PH and IH was kept equal to a mean level measured between 30 and 90 min of breathing 12% O2 in a pretest. Urine flow during PH and IH (1.81 ± 0.92 and 1.94 ± 1.03 ml/min, respectively) but not during HP (1.64 ± 0.96 ml/min) significantly exceeded that during NO (control, 1.38 ± 0.71 ml/min). Urine flow increases vs. each test day's baseline were significant with PH, IH, and HP. Differences in glomerular filtration rate, fractional sodium clearance, urodilatin, systemic blood pressure, or leg venous compliance were excluded as factors of HDR. However, slight increases in plasma and urinary endothelin-1 and epinephrine with PH and IH could play a role. In conclusion, the early HDR in humans is mainly due to hypoxia and hypocapnia. It occurs without natriuresis and is unrelated to O2 chemosensitivity (hypoxic ventilatory response).

scholarly journals ACTH Infusion Impairs Baroreflex Sensitivity—Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure

2020 ◽  
Vol 105 (7) ◽  
pp. 2345-2353
Author(s):  
Janet H Leung ◽  
Omar F Bayomy ◽  
Istvan Bonyhay ◽  
Johanna Celli ◽  
Jeffrey White ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Baroreflex Sensitivity ◽  
Autonomic Failure ◽  
Random Order ◽  
Double Blind ◽  
Clinical Research Center ◽  
Early Afternoon ◽  
Treatment Analysis ◽  
Placebo Infusion

Abstract Context Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. Objective The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1–24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. Design A double-blind, placebo-controlled, random-order, cross-over study was conducted. Setting This study took place in a clinical research center. Participants Participants included healthy men and women. Interventions Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. Main Outcome Measures Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. Results Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. Conclusions ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

Role of calcium ions in dopamine release induced by sodium cyanide perfusion in rat striatum

1993 ◽  
Vol 32 (7) ◽  
pp. 681-688 ◽  
Author(s):  
M. Matsumoto ◽  
M. Inagaki ◽  
Y. Kiuchi ◽  
J. Izumi ◽  
Y. Yamazaki ◽  
...  
Keyword(s):  
Calcium Ions ◽  
Dopamine Release ◽  
Sodium Cyanide ◽  
Rat Striatum

scholarly journals Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin

2021 ◽  
Vol 12 ◽  
Author(s):  
Friederike Holze ◽  
Isidora Avedisian ◽  
Nimmy Varghese ◽  
Anne Eckert ◽  
Matthias E. Liechti
Keyword(s):  
Random Order ◽  
Therapeutic Effects ◽  
Acute Effects ◽  
Emotional Empathy ◽  
Double Blind ◽  
Mediating Role ◽  
Oxytocin Release ◽  
Implicit And Explicit ◽  
Primary Action

The psychedelic lysergic acid diethylamide (LSD) has experienced a revival in research, including clinical trials that evaluate LSD-assisted psychotherapy. LSD induces perceptual alterations and influences emotion processing in ways that may support psychotherapy. Here, we investigated the effects of LSD on emotional empathy and mediating role of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor by administering 25, 50, 100, and 200 µg LSD alone and 200 µg LSD combined with pretreatment with the 5-HT2A receptor antagonist ketanserin (40 mg) using a placebo-controlled, double-blind, random-order, crossover design in 16 healthy subjects. The Multifaceted Empathy Test (MET) was used to assess the effects of LSD on emotional empathy. Plasma oxytocin levels were also measured. LSD dose-dependently increased implicit and explicit emotional empathy, with the highest 200 µg LSD dose having a significant effect compared with placebo. The 200 µg dose of LSD also moderately increased plasma oxytocin levels compared with placebo. Ketanserin reduced the LSD-induced elevations of oxytocin but not the LSD-induced increases in emotional empathy. These findings confirm that LSD enhances empathy, and this effect may be partially independent of its primary action on 5-HT2A receptors to induce subjective psychedelic effects. In contrast, LSD-induced oxytocin release may depend on 5-HT2A receptor stimulation, which is consistent with the psychedelic effect of LSD. Further studies are needed to investigate whether LSD may also enhance empathy and potentially produce therapeutic effects in patients who have deficits in empathy and impairments in social functioning.

scholarly journals On the relationship of first-episode psychosis to the amphetamine-sensitized state: a dopamine D2/3 receptor agonist radioligand study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ana Weidenauer ◽  
Martin Bauer ◽  
Ulrich Sauerzopf ◽  
Lucie Bartova ◽  
Lukas Nics ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Receptor Agonist ◽  
Dopamine Release ◽  
First Episode Psychosis ◽  
First Episode ◽  
Single Pair ◽  
Dopamine System ◽  
Prefrontal Cortical ◽  
Positron Emission ◽  
Episode Psychosis

AbstractSchizophrenia is characterized by increased behavioral and neurochemical responses to dopamine-releasing drugs. This prompted the hypothesis of psychosis as a state of “endogenous” sensitization of the dopamine system although the exact basis of dopaminergic disturbances and the possible role of prefrontal cortical regulation have remained uncertain. To show that patients with first-episode psychosis release more dopamine upon amphetamine-stimulation than healthy volunteers, and to reveal for the first time that prospective sensitization induced by repeated amphetamine exposure increases dopamine-release in stimulant-naïve healthy volunteers to levels observed in patients, we collected data on amphetamine-induced dopamine release using the dopamine D2/3 receptor agonist radioligand [11C]-(+)-PHNO and positron emission tomography. Healthy volunteers (n = 28, 14 female) underwent a baseline and then a post-amphetamine scan before and after a mildly sensitizing regimen of repeated oral amphetamine. Unmedicated patients with first-episode psychosis (n = 21; 6 female) underwent a single pair of baseline and then post-amphetamine scans. Furthermore, T1 weighted magnetic resonance imaging of the prefrontal cortex was performed. Patients with first-episode psychosis showed larger release of dopamine compared to healthy volunteers. After sensitization of healthy volunteers their dopamine release was significantly amplified and no longer different from that seen in patients. Healthy volunteers showed a negative correlation between prefrontal cortical volume and dopamine release. There was no such relationship after sensitization or in patients. Our data in patients with untreated first-episode psychosis confirm the “endogenous sensitization” hypothesis and support the notion of impaired prefrontal control of the dopamine system in schizophrenia.

scholarly journals Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

2020 ◽  
Vol 45 (12) ◽  
pp. 2003-2011 ◽  
Author(s):  
N. L. Mason ◽  
K. P. C. Kuypers ◽  
F. Müller ◽  
J. Reckweg ◽  
D. H. Y. Tse ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Prefrontal Cortical ◽  
Parallel Group Design ◽  
Parallel Group ◽  
Brain And Behavior ◽  
And Behavior ◽  
Glutamate System

Abstract There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

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