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Frontiers in Pharmacology 2024Caffeine and the selective A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study...
Caffeine and the selective A receptor antagonist SCH58261 both have ergogenic properties, effectively reducing fatigue and enhancing exercise capacity. This study investigates in male Swiss mice the interaction between adenosine A receptors and dopamine D receptors controlling central fatigue, with a focus on the striatum where these receptors are most abundant. We employed DPCPX and SCH58261 to antagonize A and A receptors, caffeine as a non-competitive antagonist for both receptors, and haloperidol as a D receptor antagonist; all compounds were tested upon systemic application and caffeine and SCH58261 were also directly applied in the striatum. Behavioral assessments using the open field, grip strength, and treadmill tests allowed estimating the effect of treatments on fatigue. The results suggested a complex interplay between the dopamine and adenosine systems. While systemic DPCPX had little effect on motor performance or fatigue, the application of either caffeine or SCH58261 was ergogenic, and these effects were attenuated by haloperidol. The intra-striatal administration of caffeine or SCH58261 was also ergogenic, but these effects were unaffected by haloperidol. These findings confirm a role of striatal A receptors in the control of central fatigue but suggest that the D receptor-mediated control of the ergogenic effects of caffeine and of A receptor antagonists might occur outside the striatum. This prompts the need of additional efforts to unveil the role of different brain regions in the control of fatigue.
PubMed: 38860172
DOI: 10.3389/fphar.2024.1390187 -
PeerJ 2022Animals experience stress throughout their lives and exhibit both physiological and behavioral responses to cope with it. The stress response can become harmful when...
Animals experience stress throughout their lives and exhibit both physiological and behavioral responses to cope with it. The stress response can become harmful when prolonged and increasing evidence suggests that dopamine plays a critical role in extinguishing the stress response. In particular, activation of the D2 dopamine receptor reduces glucocorticoids and increases coping behavior, , behavioral responses to adverse stimuli that reduce the harmful effects of stress. However, few studies have examined the effects of dopamine on the stress responses of wild species. We therefore tested the hypothesis that activation of the D2 dopamine receptor influences coping-like behavior in a wild-caught species. We recorded behavior of house sparrows () before and after they received injections of D2 dopamine agonists, D2 dopamine antagonists, or saline. House sparrows are common in urban environments and understanding how they cope with stress may help us better understand how animals cope with urban stressors. We found that the birds significantly increased biting of inanimate objects after the agonist but there was no change following the antagonist or saline. The biting of inanimate objects may be a mechanism of behavioral coping. This change in biting behavior was not correlated with general movement. This study supports the hypothesis that D2 dopamine receptor activation is involved in the regulation of the stress response in a wild bird.
Topics: Animals; Dopamine; Sparrows; Animals, Wild; Adaptation, Psychological
PubMed: 35795178
DOI: 10.7717/peerj.13520 -
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 -
Behavioural Pharmacology Jun 2022Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR). Despite early promising data, it recently failed to facilitate cocaine abstinence in... (Review)
Review
Lorcaserin is a modestly selective agonist for 2C serotonin receptors (5-HT2CR). Despite early promising data, it recently failed to facilitate cocaine abstinence in patients and has been compared with dopamine antagonist medications (antipsychotics). Here, we review the effects of both classes on drug reinforcement. In addition to not being effective treatments for cocaine use disorder, both dopamine antagonists and lorcaserin can have biphasic effects on dopamine and reward behavior. Lower doses can cause enhanced drug taking with higher doses causing reductions. This biphasic pattern is shared with certain stimulants, opioids, and sedative-hypnotics, as well as compounds without abuse potential that include agonists for muscarinic and melatonin receptors. Additional factors associated with decreased drug taking include intermittent dosing for dopamine antagonists and use of progressive-ratio schedules for lorcaserin. Clinically relevant doses of lorcaserin were much lower than those that inhibited cocaine-reinforced behavior and can also augment this same behavior in different species. Diminished drug-reinforced behavior only occurred in animals after higher doses that are not suitable for use in patients. In conclusion, drugs of abuse and related compounds often act as biphasic modifiers of reward behavior, especially when evaluated over a broad range of doses. This property may reflect the underlying physiology of the reward system, allowing homeostatic influences on behavior.
Topics: Animals; Benzazepines; Cocaine; Cocaine-Related Disorders; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Humans; Reward; Self Administration; Substance-Related Disorders
PubMed: 35324488
DOI: 10.1097/FBP.0000000000000672 -
Psychopharmacology Sep 2022Learning the association between rewards and predictive cues is critical for appetitive behavioral responding. The mesolimbic dopamine system is thought to play an...
RATIONALE
Learning the association between rewards and predictive cues is critical for appetitive behavioral responding. The mesolimbic dopamine system is thought to play an integral role in establishing these cue-reward associations. The dopamine response to cues can signal differences in reward value, though this emerges only after significant training. This suggests that the dopamine system may differentially regulate behavioral responding depending on the phase of training.
OBJECTIVES
The purpose of this study was to determine whether antagonizing dopamine receptors elicited different effects on behavior depending on the phase of training or the type of Pavlovian task.
METHODS
Separate groups of male rats were trained on Pavlovian tasks in which distinct audio cues signaled either differences in reward size or differences in reward rate. The dopamine receptor antagonist flupenthixol was systemically administered prior to either the first ten sessions of training (acquisition phase) or the second ten sessions of training (expression phase), and we monitored the effect of these manipulations for an additional ten training sessions.
RESULTS
We identified acute effects of dopamine receptor antagonism on conditioned responding, the latency to respond, and post-reward head entries in both Pavlovian tasks. Interestingly, dopamine receptor antagonism during the expression phase produced persistent deficits in behavioral responding only in rats trained on the reward size Pavlovian task.
CONCLUSIONS
Together, our results illustrate that dopamine's control over behavior in Pavlovian tasks depends upon one's prior training experience and the information signaled by the cues.
Topics: Animals; Conditioning, Classical; Conditioning, Operant; Cues; Dopamine; Dopamine Antagonists; Male; Rats; Rats, Sprague-Dawley; Receptors, Dopamine; Reward
PubMed: 35796814
DOI: 10.1007/s00213-022-06182-w -
Psychological Medicine Oct 2022The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been...
BACKGROUND
The hyper-function of the striatal dopamine system has been suggested to underlie key pathophysiological mechanisms in schizophrenia. Moreover, patients have been observed to present a significant elevation of dopamine receptor availability compared to healthy controls. Although it is difficult to measure dopamine levels directly in humans, neurochemical imaging techniques such as single-photon emission computed tomography (SPECT) provide indirect indices of dopamine synthesis and release, and putative synaptic levels.
METHODS
We focused on the role of dopamine postsynaptic regulation using [I] iodobenzamide (IBZM) SPECT. We compared D receptor availability between 53 healthy controls and 21 medication-naive patients with recent-onset schizophrenia.
RESULT
The mean specific striatal binding showed no significant difference between patients and controls (estimated difference = 0.001; 95% CI -0.11 to 0.11; = 0.00, df = 1, 69; = 0.99). There was a highly significant effect of age whereby IBZM binding declined with advancing age [estimated change per decade of age = -0.01(binding ratio); 95% CI -0.01 to -0.004; = 11.5, df = 1, 69; = 0.001]. No significant correlations were found between the mean specific striatal binding and psychopathological or cognitive rating scores.
CONCLUSIONS
Medication-naïve patients with recent-onset schizophrenia have similar D receptor availability to healthy controls. We suggest that, rather than focusing exclusively on postsynaptic receptors, future treatments should target the presynaptic control of dopamine synthesis and release.
Topics: Humans; Infant, Newborn; Schizophrenia; Dopamine Antagonists; Dopamine; Receptors, Dopamine D2; Corpus Striatum; Tomography, Emission-Computed, Single-Photon
PubMed: 33682657
DOI: 10.1017/S0033291720005413 -
American Journal of Physiology. Renal... Oct 2019The role of dopamine D-like receptors (DR) in the regulation of renal Na transporters, natriuresis, and blood pressure is well established. However, the involvement of...
The role of dopamine D-like receptors (DR) in the regulation of renal Na transporters, natriuresis, and blood pressure is well established. However, the involvement of the angiotensin 1-7 (ANG 1-7)-Mas receptor in the regulation of Na balance and blood pressure is not clear. The present study aimed to investigate the hypothesis that ANG 1-7 can regulate Na homeostasis by modulating the renal dopamine system. Sprague-Dawley rats were infused with saline alone (vehicle) or saline with ANG 1-7, ANG 1-7 antagonist A-779, DR agonist SKF38393, and antagonist SCH23390. Infusion of ANG 1-7 caused significant natriuresis and diuresis compared with saline alone. Both natriuresis and diuresis were blocked by A-779 and SCH23390. SKF38393 caused a significant, SCH23390-sensitive natriuresis and diuresis, and A-779 had no effect on the SKF38393 response. Concomitant infusion of ANG 1-7 and SKF38393 did not show a cumulative effect compared with either agonist alone. Treatment of renal proximal tubules with ANG 1-7 or SKF38393 caused a significant decrease in Na-K-ATPase and Na/H exchanger isoform 3 activity. While SCH23390 blocked both ANG 1-7- and SKF38393-induced inhibition, the DR response was not sensitive to A-779. Additionally, ANG 1-7 activated PKG, enhanced tyrosine hydroxylase activity via Ser phosphorylation, and increased renal dopamine production. These data suggest that ANG 1-7, via PKG, enhances tyrosine hydroxylase activity, which increases renal dopamine production and activation of DR and subsequent natriuresis. This study provides evidence for a unidirectional functional interaction between two G protein-coupled receptors to regulate renal Na transporters and induce natriuresis.
Topics: 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; Angiotensin I; Animals; Benzazepines; Cyclic GMP-Dependent Protein Kinases; Diuresis; Dopamine; Dopamine Agonists; Dopamine Antagonists; Kidney; Natriuresis; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Receptors, G-Protein-Coupled; Sodium; Sodium-Hydrogen Exchangers; Sodium-Potassium-Exchanging ATPase
PubMed: 31411069
DOI: 10.1152/ajprenal.00135.2019 -
Archives of Razi Institute Oct 2021The present study aimed to identify the role of dopaminergic and cannabinoidergic systems in the ghrelin-induced hypophagia among meat-type chickens. In the first...
The present study aimed to identify the role of dopaminergic and cannabinoidergic systems in the ghrelin-induced hypophagia among meat-type chickens. In the first experiment, intracerebroventricular (ICV) injection was applied to birds with control solution, D receptor antagonist (5 nmol), ghrelin (6 nmol), and D1 receptor antagonist plus ghrelin. The second to sixth experiments were similar to the first one, with the difference that D receptor antagonist (5 nmol), D receptor antagonist (6.4 nmol), D receptor antagonist (6 nmol), the precursor of dopamine (125 nmol), and 6-hydroxy dopamine (150 nmol) instead of D antagonist were injected into the broiler chickens. In experiment 7, control solution and different levels of ghrelin antagonists (5, 10, and 20 nmol) were injected. In experiment 8, the chickens were ICV injected with control solution, ghrelin antagonist (10 nmol), dopamine (40 nmol), and ghrelin antagonist plus dopamine. In experiments 9 and 10, CB and CB receptors antagonist (6.25µg and 5µg) were co-injected with ghrelin (6 nmol), respectively, measuring the food intake for 120 min after the injection. It was observed that ghrelin ICV injection considerably reduced food intake, whereas ghrelin antagonist increased food intake, depending on the dose (P<0.05). In addition, ghrelin-induced hypophagia was significantly attenuated by D receptor antagonist and 6-hydroxy dopamine (P<0.05), while the dopamine precursor considerably elevated the ghrelin-induced food intake (P<0.05). The dopamine-induced feeding behavior was diminished by the co-administration of [D-Lys-3]-GHRP-6 (10 nmol)+dopamine (40 nmol) (P<0.05). In addition, CB receptor antagonists enhanced the ghrelin influence on food intake (P<0.05). The results implied that the hypophagic impact of ghrelin was probably mediated by D and CB receptors within neonatal broilers.
Topics: Animals; Chickens; Dopamine; Eating; Ghrelin; Receptors, Cannabinoid; Receptors, Dopamine
PubMed: 35096329
DOI: 10.22092/ari.2020.351261.1514 -
Nature Communications Sep 2023Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation...
Dopamine fundamentally contributes to reinforcement learning, but recent accounts also suggest a contribution to specific action selection mechanisms and the regulation of response vigour. Here, we examine dopaminergic mechanisms underlying human reinforcement learning and action selection via a combined pharmacological neuroimaging approach in male human volunteers (n = 31, within-subjects; Placebo, 150 mg of the dopamine precursor L-dopa, 2 mg of the D2 receptor antagonist Haloperidol). We found little credible evidence for previously reported beneficial effects of L-dopa vs. Haloperidol on learning from gains and altered neural prediction error signals, which may be partly due to differences experimental design and/or drug dosages. Reinforcement learning drift diffusion models account for learning-related changes in accuracy and response times, and reveal consistent decision threshold reductions under both drugs, in line with the idea that lower dosages of D2 receptor antagonists increase striatal DA release via an autoreceptor-mediated feedback mechanism. These results are in line with the idea that dopamine regulates decision thresholds during reinforcement learning, and may help to bridge action selection and response vigor accounts of dopamine.
Topics: Humans; Male; Dopamine; Levodopa; Haloperidol; Men; Plastic Surgery Procedures
PubMed: 37666865
DOI: 10.1038/s41467-023-41130-y -
Scientific Reports Nov 2019Clinical use of olanzapine frequently causes severe hyperglycemia as an adverse effect. In this study, we elucidated mechanisms by which olanzapine reduced insulin...
Clinical use of olanzapine frequently causes severe hyperglycemia as an adverse effect. In this study, we elucidated mechanisms by which olanzapine reduced insulin secretion using the hamster pancreatic β-cell line HIT-T15. Reverse transcriptional-PCR analysis revealed expression of dopamine (D, D and D), serotonin (5-HT, 5-HT, 5-HT, and 5-HT), and histamine (H and H) receptors in HIT-T15 cells. Olanzapine decreased insulin secretion from HIT-T15 cells at clinically relevant concentrations (64-160 nM). A dopamine D agonist, D antagonist, and D antagonist suppressed insulin secretion, whereas a D antagonist and D agonist increased it. A serotonin 5-HT agonist slightly increased insulin secretion, while a 5-HT antagonist slightly decreased it. Other agonists and antagonists for serotonin receptors did not affect insulin secretion. A histamine H agonist increased insulin secretion, whereas an H antagonist and H agonist suppressed it. Our results suggest that dopamine (D, D and D), serotonin (5-HT and 5-HT), and histamine (H and H) receptors, which are expressed on pancreatic β-cells, directly modulate insulin secretion from pancreatic β-cells. Thus, olanzapine may induce hyperglycemia in clinical settings by suppressing insulin secretion from pancreatic β-cells through inhibition of dopamine D, serotonin 5-HT and 5-HT, and histamine H receptors.
Topics: Insulin Secretion; Insulin-Secreting Cells; RNA, Messenger; Receptors, Biogenic Amine; Receptors, Dopamine; Receptors, Histamine; Receptors, Serotonin
PubMed: 31712714
DOI: 10.1038/s41598-019-52590-y