Background: Current medical management of endometriosis leads to suppression of ovulation and will not be helpful for women with endometriosis who are desirous of pregnancy. Thus, drugs that can both treat endometriosis and its associated infertility are highly warranted. Objective: Anti-angiogenic agents are potential drugs for patients with endometriosis and infertility. Among these drugs, dopamine agonist (DA) is promising since it does not interfere with ovulation, is safe, and not teratogenic. The aim of the study is to determine the efficacy and safety of DA for improving reproductive outcomes in women with endometriosis and infertility. Methods: A qualitative narrative review was done from inception to July 31, 2022 using the appropriate MeSH terms in PubMed, Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials, ClinicalTrial.gov, and World Health Organization International Clinical Trials Registry Platform. Date analysis was through qualitative analysis and synthesis of researches and their outcome measures. Results: No studies used the core outcomes for trials evaluating treatments for infertility associated with endometriosis. All the included articles in the review supported the possible anti-angiogenic effects of DA on the vascular endothelial growth factor [VEGF] /VEGF receptor system. The use of DA does not have an effect on ovulation and menstrual cyclicity. Studies on safety profile of DA were consistent with existing data. Conclusion Most of studies reviewed demonstrated that DA were effective in reducing endometriotic lesions. However, further research is required to establish whether this anti-angiogenic effect can improve reproductive outcomes in women with endometriosis-associated infertility.
Endometriosis ; Dopamine Agonists ; Infertility ; Angiogenesis Inducing Agents ; Angiogenesis Inhibitors

Antidepressive Agents/therapeutic use* ; Serotonin ; Serotonin Plasma Membrane Transport Proteins

L-dopa (l-3,4-dihydroxyphenylalanine)-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy for Parkinson's disease. The potential contribution of striatal D₂ receptor (D₂R)-positive neurons and downstream circuits in the pathophysiology of LID remains unclear. In this study, we investigated the role of striatal D₂R⁺ neurons and downstream globus pallidus externa (GPe) neurons in a rat model of LID. Intrastriatal administration of raclopride, a D₂R antagonist, significantly inhibited dyskinetic behavior, while intrastriatal administration of pramipexole, a D₂-like receptor agonist, yielded aggravation of dyskinesia in LID rats. Fiber photometry revealed the overinhibition of striatal D₂R⁺ neurons and hyperactivity of downstream GPe neurons during the dyskinetic phase of LID rats. In contrast, the striatal D₂R⁺ neurons showed intermittent synchronized overactivity in the decay phase of dyskinesia. Consistent with the above findings, optogenetic activation of striatal D₂R⁺ neurons or their projections in the GPe was adequate to suppress most of the dyskinetic behaviors of LID rats. Our data demonstrate that the aberrant activity of striatal D₂R⁺ neurons and downstream GPe neurons is a decisive mechanism mediating dyskinetic symptoms in LID rats.
Rats ; Animals ; Levodopa/toxicity* ; Dopamine ; Parkinsonian Disorders/drug therapy* ; Oxidopamine ; Dyskinesia, Drug-Induced ; Corpus Striatum/metabolism* ; Neurons/metabolism* ; Receptors, Dopamine D2/metabolism* ; Antiparkinson Agents/toxicity*

Opioid use disorder (OUD) has become a considerable global public health challenge; however, potential medications for the management of OUD that are effective, safe, and nonaddictive are not available. Accumulating preclinical evidence indicates that antagonists of the dopamine D₃ receptor (D₃R) have effects on addiction in different animal models. We have previously reported that YQA14, a D₃R antagonist, exhibits very high affinity and selectivity for D₃Rs over D₂Rs, and is able to inhibit cocaine- or methamphetamine-induced reinforcement and reinstatement in self-administration tests. In the present study, our results illustrated that YQA14 dose-dependently reduced infusions under the fixed-ratio 2 procedure and lowered the breakpoint under the progressive-ratio procedure in heroin self-administered rats, also attenuated heroin-induced reinstatement of drug-seeking behavior. On the other hand, YQA14 not only reduced morphine-induced expression of conditioned place preference but also facilitated the extinguishing process in mice. Moreover, we elucidated that YQA14 attenuated opioid-induced reward or reinforcement mainly by inhibiting morphine-induced up-regulation of dopaminergic neuron activity in the ventral tegmental area and decreasing dopamine release in the nucleus accumbens with a fiber photometry recording system. These findings suggest that D₃R might play a very important role in opioid addiction, and YQA14 may have pharmacotherapeutic potential in attenuating opioid-induced addictive behaviors dependent on the dopamine system.
Rats ; Mice ; Animals ; Analgesics, Opioid ; Dopamine ; Heroin/pharmacology* ; Dopamine Antagonists/pharmacology* ; Receptors, Dopamine D3/metabolism* ; Morphine/pharmacology* ; Behavior, Addictive/drug therapy* ; Self Administration

Purinergic P2Y Receptor Antagonists ; Consensus ; Cardiovascular System ; Cardiology ; Asia

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.
Rats ; Male ; Animals ; Moxibustion ; Rats, Sprague-Dawley ; Rats, Wistar ; Serotonin ; Hippocampus ; Dopamine ; Norepinephrine ; Neurotransmitter Agents

The degeneration of monoaminergic system and the reduction of monoamine neurotransmitters(MNTs) are associated with the occurrence of a variety of neuropsychiatric diseases, becoming the key indicators for clinical diagnosis and treatment. Recent studies suggested gut microbiota could influence the occurrence, development, and treatment of neuropsychiatric diseases by directly or indirectly regulating the synthesis and metabolism of MNTs. Rich clinical experience has been accumulated in the amelioration and treatment of neuropsychiatric diseases by traditional Chinese medicines. The traditional oral administration method demonstrates obvious advantages in regulating gut microbiota. It provides a new idea for explaining the pharmacodynamic material basis and mechanism of traditional Chinese medicines in ameliorating neuropsychiatric disease by improving the levels of MNTs via gut microbiota regulation. Focusing on three common neuropsychiatric diseases including Alzheimer's disease, Parkinson's disease, and major depression, we summarized the pathways of gut microbiota in regulating the levels of MNTs and the paradigms of traditional Chinese medicines in ameliorating neuropsychiatric diseases via the "bacteria-gut-brain axis", aiming to provide ideas for the development of drugs and treatment schemes.
Humans ; Administration, Oral ; Alzheimer Disease ; Brain-Gut Axis ; Gastrointestinal Microbiome ; Neurotransmitter Agents

This study used m-chloropheniperazine(MCPP) and chronic unforeseeable mild stress(CUMS) to induce the rat models of anxiety and depression, respectively. The behaviors of rats were observed by the open field test(OFT), light-dark exploration test(LDE), tail suspension test(TST), and forced swimming test(FST), and the antidepressant and anxiolytic effects of agarwood essential oil(AEO), agarwood fragrant powder(AFP), and agarwood line incense(ALI) were explored. The enzyme-linked immunosorbent assay(ELISA) was used to determine the levels of 5-hydroxytryptamine(5-HT), glutamic acid(Glu), and γ-aminobutyric acid(GABA_A) in the hippocampal area. The Western blot assay was used to determine the protein expression levels of glutamate receptor 1(GluR1) and vesicular glutamate transporter type 1(VGluT1), exploring the anxiolytic and antidepressant mechanism of agarwood inhalation. The results showed that compared with the anxiety model group, the AEO, AFP, and ALI groups decreased the total distance(P<0.05), decreased the velocity of movements(P<0.05), prolonged the immobile time(P<0.05), and reduced the distance and velocity of the rat model of anxiety in the dark box(P<0.05). Compared with the depression model group, the AEO, AFP, and ALI groups increased the total distance and average velocity(P<0.05), reduced the immobile time(P<0.05), and reduced the forced swimming and tail suspension time(P<0.05). In terms of transmitter regulation, the AEO, AFP, and ALI groups decreased the level of Glu in the rat model of anxiety(P<0.05) and increased the levels of GABA_A and 5-HT(P<0.05), while the AEO, AFP, and ALI groups all increased the level of 5-HT in the rat model of depression(P<0.05) and decreased the levels of GABA_A and Glu(P<0.05). At the same time, the AEO, AFP, and ALI groups all increased the protein expression levels of GluR1 and VGluT1 in the hippocampus of the rat models of anxiety and depression(P<0.05). In conclusion, AEO, AFP, and ALI exert anxiolytic and antidepressant effects, and the mechanism might be related to the regulation of the neurotransmitter and the protein expression of GluR1 and VGluT1 in the hippocampus.
Animals ; Rats ; Anti-Anxiety Agents ; Serotonin ; alpha-Fetoproteins ; Antidepressive Agents ; Glutamic Acid ; gamma-Aminobutyric Acid

To investigate the antidepressant mechanism of Shenling Kaixin Granules(SLKX) in treating chronic unpredictable mild stress(CUMS) model rats. Ninety male SD rats were randomly divided into control group, model group, Shugan Jieyu Capsules(110 mg·kg~(-1)) group and SLKX low-(90 mg·kg~(-1)), medium-(180 mg·kg~(-1)), and high-dose(360 mg·kg~(-1)) groups. Depression rat model was replicated by CUMS method. After treatment, the behavioral changes of rats were evaluated by sugar preference, open field, elevated cross maze and forced swimming experiments. The contents of interleukin 1 beta(IL-1β), tumor necrosis factor α(TNF-α), brain-derived neurotrophic factor(BDNF) and 5-hydroxytryptamine(5-HT) in serum were determined by enzyme linked immunosorbent assay(ELISA), and the activities of superoxide dismutase(SOD) and catalase(CAT) in hippocampal CA1 region were also detected. Pathological changes in hippocampal CA1 region were detected by hematoxylin-eosin(HE) staining, and Western blot was used to determine the expression of nerve growth factor(NGF), BDNF, phospho-tyrosine kinase receptor(p-TrkB)/TrkB, phospho-cAMP-response element binding protein(p-CREB)/CREB, nuclear factor E2 related factor 2(Nrf2), heme oxygenase 1(HO-1), B-cell lymphoma-2(Bcl-2)/Bcl-2 associated X protein(Bax) and caspase-3 in hippocampal CA1 region. RESULTS:: showed that compared with the control group, the model group had decreased sugar preference, reduced number of entries and time spent in the center of open field and shortened total distance of movement, reduced number of entries and proportion of time spent in open arm, and increased number and time of immobility in forced swimming experiment. Additionally, the serum contents of IL-1β and TNF-α and the expression of caspase-3 were higher, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1 and Bcl-2/Bax, and the Nrf2 nuclear translocation were lower in model group than in control group. Compared with the conditions in model group, the sugar preference, the number of entries and time spent in the center of open, total distance of movement, and the number of entries and proportion of time spent in open arm in treatment groups were increased while the number and time of immobility in forced swimming experiment were decreased; the serum contents of IL-1β and TNF-α and the expression of caspase-3 were down regulated, while the contents of BDNF and 5-HT, the activities of SOD and CAT in hippocampal CA1 region, the expressions of NGF, BDNF, p-TrkB/TrkB, p-CREB/CREB, HO-1, Bcl-2/Bax, and Nrf2 nuclear translocation were enhanced. In conclusion, SLKX might regulate the Nrf2 nucleus translocation by activating BDNF/TrkB/CREB pathway, lower oxidative stress damage in hippocampus, inhibit caspase-3 activity, and reduce apoptosis of hippocampal nerve cells, thereby playing an antidepressant role.
Rats ; Male ; Animals ; bcl-2-Associated X Protein/metabolism* ; Caspase 3/metabolism* ; Nerve Growth Factor/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Signal Transduction ; Tumor Necrosis Factor-alpha/metabolism* ; Serotonin/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Antidepressive Agents/pharmacology* ; Hippocampus/metabolism* ; Superoxide Dismutase/metabolism* ; Sugars/pharmacology* ; Depression/genetics* ; Stress, Psychological/metabolism*

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.
Humans ; Hippocampus/physiology* ; Anxiety ; Anxiety Disorders ; Neurotransmitter Agents ; Neuropeptides