Melatonin Blocks Morphine-Induced Place Preference: Involvement of GLT-1, NF-κB, BDNF, and CREB in the Nucleus Accumbens

Opioid addiction remains a widespread issue despite continuous attempts by the FDA to help maintain abstinence. Melatonin is a neurohormone considered to be involved only in the neuroendocrine and reproductive systems; however, recent reports have demonstrated its potential to attenuate drug addiction and dependence. Cumulative studies have suggested that melatonin can attenuate the rewarding effects of several drugs of abuse, including opioids. This study aimed to investigate the effect of melatonin (50 mg/kg) on morphine (5 mg/kg) to produce place preference. We also investigated the effect of melatonin and morphine on the expression of GLT-1, BDNF, NF-κB, and CREB within the nucleus accumbens. Male Wistar rats were divided into control, morphine, melatonin, and the morphine + melatonin groups. The study involved a two-phase habituation phase from day 1 to day 3 and an acquisition phase from day 5 to day 14. The conditioned place preference (CPP) score, distance traveled, resting time, ambulatory count, and total activity count were measured for all animals. Rats that received morphine showed a significant increase in CPP score compared to those in the control group. Morphine treatment reduced the mRNA expression of GLT-1, BDNF, and CREB and increased that of NF-κB. However, melatonin treatment administered 30 min before morphine treatment attenuated morphine place preference and reversed GLT-1, BDNF, NF-κB, and CREB expression levels. In conclusion, the study results indicate, for the first time, the new potential targets of melatonin in modulating morphine-induced CPP.

Download Full-text

Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine release in the nucleus accumbens of rats

10.1101/2020.10.13.338343 ◽

2020 ◽

Author(s):

William N. Sanchez ◽

Jose A. Pochapski ◽

Leticia F. Jessen ◽

Marek Ellenberger ◽

Rainer K. Schwarting ◽

...

Keyword(s):

Locomotor Activity ◽

Nucleus Accumbens ◽

Dopamine Release ◽

Ultrasonic Vocalizations ◽

Control Group ◽

List Type ◽

Adult Rats ◽

Fast Scan Cyclic Voltammetry ◽

Entire Duration ◽

Male Wistar Rats

AbstractBackground and PurposeCurrently, no effective drug exists to treat cocaine use disorders, which affect millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine release in the nucleus accumbens of rodents. In addition, we have recently shown that diazepam blocks the increase in dopamine release and the affective marker 50-kHz ultrasonic vocalizations (USV) induced by DL-amphetamine in rats.Experimental ApproachHere we tested whether administration of 2.5 mg·kg−1 diazepam (i.p.) in adult male Wistar rats could block the effects of 20 mg·kg−1 cocaine (i.p.) on electrically evoked phasic dopamine release in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity.Key ResultsCocaine injection increased evoked dopamine release up to 3-fold within 5 min and the increase was significantly higher than baseline for at least 90 min. The injection of diazepam 15 min later attenuated the cocaine effect by nearly 50% and this attenuation was maintained for at least 30 min. Stimulant drugs, natural rewards and reward predictive cues are known to evoke 50-kHz USV in adult rats. In the present study, cocaine increased the number of 50-kHz USV of the flat, step, trill, and mixed kinds by 12-fold. This effect was at maximum 5 min after cocaine injection, decreased with time and lasted at least 40 min. Diazepam significantly blocked this effect for the entire duration of the session. The distance travelled by control rats during a 40-min session of exploration in an open field was at maximum in the first 5 min and decayed progressively until the end of the session. Cocaine-treated rats travelled significantly longer distances when compared to the control group, while diazepam significantly attenuated cocaine-induced locomotion by up to 50%.Conclusions and implicationThese results suggest that the neurochemical, affective, and stimulant effects of cocaine can be mitigated by diazepam.What is already knownDiazepam decreases dopamine release in the rodent nucleus accumbens (NAc) and reduces some effects produced by DL-amphetamine.What this study addsDiazepam attenuated the increase in phasic dopamine release caused by cocaine.Diazepam blocked the effect of cocaine on 50-kHz USV and locomotor activity.Clinical significanceThis study demonstrates that diazepam can block specific effects of cocaine that likely contribute to addiction.

Download Full-text

Melanin-concentrating hormone in rat nucleus accumbens or lateral hypothalamus differentially impacts morphine and food seeking behaviors

Journal of Psychopharmacology ◽

10.1177/0269881119895521 ◽

2020 ◽

Vol 34 (4) ◽

pp. 478-489 ◽

Cited By ~ 1

Author(s):

Dongmei Wang ◽

Jianjun Zhang ◽

Yunjing Bai ◽

Xigeng Zheng ◽

Mirmohammadali M Alizamini ◽

...

Keyword(s):

Nucleus Accumbens ◽

Conditioned Place Preference ◽

Lateral Hypothalamus ◽

Drugs Of Abuse ◽

Inhibitory Effect ◽

Place Preference ◽

Sprague Dawley ◽

Nucleus Accumbens Shell ◽

Melanin Concentrating Hormone ◽

Natural Rewards

Background: Identifying neural substrates that are differentially affected by drugs of abuse and natural rewards is key to finding a target for an efficacious treatment for substance abuse. Melanin-concentrating hormone is a polypeptide with an inhibitory effect on the mesolimbic dopamine system. Here we test the hypothesis that melanin-concentrating hormone in the lateral hypothalamus and nucleus accumbens shell is differentially involved in the regulation of morphine and food-rewarded behaviors. Methods: Male Sprague–Dawley rats were trained with morphine (5.0 mg/kg, subcutaneously) or food pellets (standard chow, 10–14 g) to induce a conditioned place preference, immediately followed by extinction training. Melanin-concentrating hormone (1.0 µg/side) or saline was infused into the nucleus accumbens shell or lateral hypothalamus before the reinstatement primed by morphine or food, and locomotor activity was simultaneously monitored. As the comparison, melanin-concentrating hormone was also microinjected into the nucleus accumbens shell or lateral hypothalamus before the expression of food or morphine-induced conditioned place preference. Results: Microinfusion of melanin-concentrating hormone into the nucleus accumbens shell (but not into the lateral hypothalamus) prevented the reinstatement of morphine conditioned place preference but had no effect on the reinstatement of food conditioned place preference. In contrast, microinfusion of melanin-concentrating hormone into the lateral hypothalamus (but not in the nucleus accumbens shell) inhibited the reinstatement of food conditioned place preference but had no effect on the reinstatement of morphine conditioned place preference. Conclusions: These results suggest a clear double dissociation of melanin-concentrating hormone in morphine/food rewarding behaviors and melanin-concentrating hormone in the nucleus accumbens shell. Melanin-concentrating hormone could be a potential target for therapeutic intervention for morphine abuse without affecting natural rewards.

Download Full-text

The Role of mGluR4 Receptors Within the Nucleus Accumbens in the Acquisition and Expression of Morphine-induced Conditioned Place Preference in Male Rats

10.21203/rs.3.rs-147897/v1 ◽

2021 ◽

Author(s):

Zahra Ebrahimi ◽

Nazanin Kahvandi ◽

Alireza Komaki ◽

Seyed Asaad Karimi ◽

Marzieh Naderishahab ◽

...

Keyword(s):

Nucleus Accumbens ◽

Metabotropic Glutamate Receptors ◽

Place Preference ◽

Male Rats ◽

Dependent Manner ◽

Metabotropic Glutamate ◽

Male Wistar Rats ◽

Glutamate Neurotransmission ◽

Reward Pathways

Abstract Background: Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). Also, metabotropic glutamate receptors (mGluRs) into the NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study we investigated the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats. Animals were bilaterally implanted with guide cannulae above the NAc. In the first part of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the next part of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test to check the effect of VU0155041 on the expression of morphine-induced CPP. Results: The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression Our data indicated that intra-NAc administration of VU0155041 dose-dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine.These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

Download Full-text

Evaluation of Sub-acute and Sub Chronic Toxicity Profile of the Aqueous Leaf Crude Extract of Melanthera Scandens (Schumach & Thonn) in Wistar Rats

Journal of Complementary and Alternative Medical Research ◽

10.9734/jocamr/2019/v8i330124 ◽

2019 ◽

pp. 1-16

Author(s):

Daniel Chans Mwandah ◽

Ibrahim Ntulume ◽

Adamu Almustapha Aliero ◽

Kennedy Kiyimba ◽

Emmanuel Tiyo Ayikobua ◽

...

Keyword(s):

Acute Toxicity ◽

Crude Extract ◽

Wistar Rats ◽

Control Group ◽

Subchronic Toxicity ◽

Significant Treatment ◽

Study Results ◽

Need To Evaluate ◽

Female Wistar Rats ◽

Male Wistar Rats

Aims: Although Melanthera scandens is a plant widely used in traditional medicine for the management of seizures, stomach ulcers and sores, dysmenorrhea, diabetes and malaria, there was scanty information about its safety. There was, therefore, a need to evaluate the sub-acute and subchronic toxicity studies of this plant which would reflect on its safety. Methodology: This was an experimental laboratory study. The research was conducted at Kampala International University-Western Campus at the Pharmacology laboratory from February to June 2017. The sub-acute toxicity was evaluated after administering daily oral doses of M. scandens crude extract (250, 500 and 1000 mg/kg) for 28 days and 90 days for subchronic study, after which the effect on haematological, biochemical and histopathological parameters were assessed in male and female Wistar rats (five of each sex). Results: Sub-acute toxicity results revealed that there was a significant decrease in the AST between the male Wistar rats that received 250 mg/kg (P= .005) and those that received 500 mg/kg (P= .05) as compared with the control group. Subchronic studies showed a significant increase in ALP (P= .05) at 1000 mg/kg compared with 500 mg/kg. Terminal necropsy did not reveal any treatment-related histopathological findings. There were also no toxicologically significant treatment-related effects on haematological parameters. The sub-acute toxicity results suggest that doses of 250mg/kg and 500mg/kg are safe and could be hepatoprotective due to reduced levels of AST and ALP, while the subchronic toxicity study results suggest that doses greater than 1000 mg/kg could be toxic to the plasma membrane, liver cells or endoplasmic reticulum due to increased ALP levels at this dose. Conclusion: The M. scandens crude extract did not cause significant toxicity on haematological and histopathological indices, after sub-acute and subchronic administration in Wistar rats.

Download Full-text

Loss of β-arrestin2 in D2 cells alters neuronal excitability in the nucleus accumbens and behavioral responses to psychostimulants and opioids

10.1101/685719 ◽

2019 ◽

Author(s):

Kirsten A. Porter-Stransky ◽

Alyssa K. Petko ◽

Saumya L. Karne ◽

L. Cameron Liles ◽

Nikhil M. Urs ◽

...

Keyword(s):

Nucleus Accumbens ◽

G Protein ◽

Conditioned Place Preference ◽

Neuronal Excitability ◽

Drugs Of Abuse ◽

Behavioral Responses ◽

Place Preference ◽

Locomotor Sensitization ◽

Drug Induced ◽

G Protein Coupled

AbstractPsychostimulants and opioids increase dopamine (DA) neurotransmission, activating D1 and D2 G protein-coupled receptors. β-arrestin2 (βarr2) desensitizes and internalizes these receptors and initiates G protein-independent signaling. Previous work revealed that mice with a global or cell-specific knockout of βarr2 have altered responses to certain drugs; however, the effects of βarr2 on the excitability of medium spiny neurons (MSNs) and its role in mediating the rewarding effects of drugs of abuse are unknown. D1-Cre and D2-Cre transgenic mice were crossed with floxed βarr2 mice to eliminate βarr2 specifically in cells containing either D1 (D1βarr2-KO) or D2 (D2βarr2-KO) receptors. We used slice electrophysiology to characterize the role of βarr2 in modulating D1 and D2 nucleus accumbens MSN intrinsic excitability in response to DA and tested the locomotor-activating and rewarding effects of cocaine and morphine in these mice. We found that eliminating βarr2 attenuated the ability of DA to inhibit D2-MSNs but had little effect on the DA response of D1-MSNs. While D1βarr2-KO mice had mostly normal drug responses, D2βarr2-KO mice showed dose-dependent reductions in acute locomotor responses to cocaine and morphine, attenuated locomotor sensitization to cocaine, and blunted cocaine reward measured with conditioned place preference. Both D2βarr2-KO and D1βarr2-KO mice displayed an enhanced conditioned place preference for the highest dose of morphine. These results indicate that D2-derived βarr2 functionally contributes to the ability of DA to inhibit D2-MSNs and multiple behavioral responses to psychostimulants and opioids, while loss of βarr2 in D1 neurons has little impact on D1-MSN excitability or drug-induced behaviors.

Download Full-text

The role of mGlu4 receptors within the nucleus accumbens in acquisition and expression of morphine-induced conditioned place preference in male rats

BMC Neuroscience ◽

10.1186/s12868-021-00627-2 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Zahra Ebrahimi ◽

Nazanin Kahvandi ◽

Alireza Komaki ◽

Seyed Asaad Karimi ◽

Marzieh Naderishahab ◽

...

Keyword(s):

Nucleus Accumbens ◽

Metabotropic Glutamate Receptors ◽

Place Preference ◽

Male Rats ◽

Dependent Manner ◽

Metabotropic Glutamate ◽

Male Wistar Rats ◽

Glutamate Neurotransmission ◽

Reward Pathways

Abstract Background Several studies have shown that glutamate neurotransmission in the nucleus accumbens (NAc) is required for the development of morphine-induced conditional place preference (CPP). In addition, metabotropic glutamate receptors (mGluRs) in NAc play important roles in the reward pathways. However, the precise role of mGluR4 in different steps of the morphine-induced CPP is less well known. In the present study the effect of bilateral intra-accumbal infusion of VU0155041, as a specific mGluR4 agonist on the acquisition and expression of morphine induced CPP in male Wistar rats was investigated. The animals were bilaterally implanted with guide cannulae above the NAc. In the first step of the study, the VU0155041 was administered at doses of 10, 30 and 50 μg/0.5 μL saline per side into the NAc during the 3 days of morphine (5 mg/kg) conditioning (acquisition) phase of morphine-induced CPP. In the second step of the study, the rats bilaterally received VU0155041 at the dose of 50 μg/0.5 μL, 5 min before the post-conditioning test in order to check the effect of VU0155041 on the expression of morphine-induced CPP. Results The results showed that the intra-accumbal injection of VU0155041 inhibits the acquisition of morphine-induced CPP in a dose dependent manner, but had no effect on expression. Conclusions The data indicated that intra-NAc administration of VU0155041 dose dependently blocks the establishment of morphine-induced CPP and reduces the rewarding properties of morphine. These effects may be related to changes in glutamate activity in the NAC and/or learning dependent mechanism of glutamate neurotransmission in reward pathway(s).

Download Full-text

Chronic immobilization stress induces anxiety-related behaviors and affects brain essential minerals in male rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000682 ◽

2020 ◽

pp. 1-8

Author(s):

Zafer Sahin ◽

Alpaslan Ozkurkculer ◽

Omer Faruk Kalkan ◽

Ahmet Ozkaya ◽

Aynur Koc ◽

...

Keyword(s):

Immobilization Stress ◽

Central Area ◽

Essential Elements ◽

Male Rats ◽

Control Group ◽

Male Wistar Rats ◽

Swimming Test ◽

The Brain ◽

Center Area ◽

Chronic Immobilization Stress

Abstract. Alterations of essential elements in the brain are associated with the pathophysiology of many neuropsychiatric disorders. It is known that chronic/overwhelming stress may cause some anxiety and/or depression. We aimed to investigate the effects of two different chronic immobilization stress protocols on anxiety-related behaviors and brain minerals. Adult male Wistar rats were divided into 3 groups as follows ( n = 10/group): control, immobilization stress-1 (45 minutes daily for 7-day) and immobilization stress-2 (45 minutes twice a day for 7-day). Stress-related behaviors were evaluated by open field test and forced swimming test. In the immobilization stress-1 and immobilization stress-2 groups, percentage of time spent in the central area (6.38 ± 0.41% and 6.28 ± 1.03% respectively, p < 0.05) and rearing frequency (2.75 ± 0.41 and 3.85 ± 0.46, p < 0.01 and p < 0.05, respectively) were lower, latency to center area (49.11 ± 5.87 s and 44.92 ± 8.04 s, p < 0.01 and p < 0.01, respectively), were higher than the control group (8.65 ± 0.49%, 5.37 ± 0.44 and 15.3 ± 3.32 s, respectively). In the immobilization stress-1 group, zinc (12.65 ± 0.1 ppm, p < 0.001), magnesium (170.4 ± 1.7 ppm, p < 0.005) and phosphate (2.76 ± 0.1 ppm, p < 0.05) levels were lower than the control group (13.87 ± 0.16 ppm, 179.31 ± 1.87 ppm and 3.11 ± 0.06 ppm, respectively). In the immobilization stress-2 group, magnesium (171.56 ± 1.87 ppm, p < 0.05), phosphate (2.44 ± 0.07 ppm, p < 0.001) levels were lower, and manganese (373.68 ± 5.76 ppb, p < 0.001) and copper (2.79 ± 0.15 ppm, p < 0.05) levels were higher than the control group (179.31 ± 1.87 ppm, 3.11 ± 0.06 ppm, 327.25 ± 8.35 ppb and 2.45 ± 0.05 ppm, respectively). Our results indicated that 7-day chronic immobilization stress increased anxiety-related behaviors in both stress groups. Zinc, magnesium, phosphate, copper and manganese levels were affected in the brain.

Download Full-text

Dietary Calcium Supplementation Suppresses Bone Formation in Magnesium-Deficient Rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831.76.3.111 ◽

2006 ◽

Vol 76 (3) ◽

pp. 111-116 ◽

Cited By ~ 3

Author(s):

Hiroshi Matsuzaki ◽

Misao Miwa

Keyword(s):

Bone Formation ◽

Calcium Supplementation ◽

Control Diet ◽

Formation Rate ◽

Dietary Calcium ◽

Mineral Apposition Rate ◽

Control Group ◽

Deficient Diet ◽

Bone Formation Rate ◽

Male Wistar Rats

The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg - and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg - and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg - and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg - group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats.

Download Full-text

Penatalaksanaan IMD pada Ibu Postpartum Sectio Caesarea Mempengaruhi Status Gizi dan Kecepatan Produksi ASI

Jurnal Bidan Cerdas (JBC) ◽

10.33860/jbc.v2i2.68 ◽

2020 ◽

Vol 2 (2) ◽

pp. 112-120

Author(s):

Nursari Abdul Syukur ◽

Susi Purwanti

Keyword(s):

Breast Milk ◽

Nutritional Status ◽

Milk Production ◽

Quantitative Research ◽

Milk Protein ◽

Sectio Caesarea ◽

Control Group ◽

P Value ◽

Study Results

Many mothers who give birth to Sectio Caesarea (SC) do not Initiate Early Breastfeeding (IMD), which fails exclusive breastfeeding. This study aimed to determine the effect of IMD management in postpartum SC mothers on nutritional status, speed of milk production, and quality of breast milk protein. Method: quantitative research with quasi approach experiment. The research design used was a pre-post-test control non-equivalent control group. A sampling of this study used the Consecutive method sampling with a sample of 20 mothers who gave birth by cesarean section (SC). Hypothesis testing uses the independent t-test and the Mann-Whitney test. The study results showed an influence on the management of IMD in postpartum SC mothers on the speed of ASI production (p-value=0.004) and nutritional status (p-value=0.028). There was no effect of IMD management on postpartum SC mothers on the quality of breast milk protein (p-value = 0.543). This study recommends that the hospital implement an IMD promotion program before the abdominal wall is closed as a form of intervention to increase milk production and maternal nutritional status

Download Full-text

Modern approaches to the treatment of mastitis in women of reproductive age

HEALTH OF WOMAN ◽

10.15574/hw.2016.111.101 ◽

2016 ◽

pp. 191-108

Author(s):

A.A. Sukhanova ◽

◽

Yu.M. Melnik ◽

O.O. Karlova ◽

◽

...

Keyword(s):

Ultrasound Examination ◽

Clinical Signs ◽

Reproductive Age ◽

Herbal Remedies ◽

Control Group ◽

Women Of Reproductive Age ◽

Clinical Method ◽

Gynecological Examination ◽

Study Results ◽

Observation Period

The aim of the study: to study the efficacy and safety of use Mastofemin in the treatment of various forms of mastitis in women of reproductive age. Materials and methods. The study included 62 women of reproductive age (mean age of 33.5±2.3 years) who were screened in the Kiev city center reproductive and perinatal medicine. Women were divided into 2 groups. The first (main) group consisted of 32 patients who received the proposed treatment using herbal remedies Mastofemin 1 capsule 2 times per day for 3 months; 30 patients of the second (control) group were under observation and received no treatment. These groups were representative and homogeneous on age, clinical symptoms and sonographic characteristics. The clinical method included evaluation of complaints of patients, anamnesis, presence of concomitant gynecologic pathology, inspection, palpation of the lymph nodes and the breast and obtaining a discharge from the nipples to conduct cytological examination, which allowed excluding from the study women with suspected malignancy of the process. All the patients were performed ultrasound examination of the breast. The review was supplemented with vaginal gynecological examination and ultrasound examination of small pelvis organs to assess the condition of the uterus and its appendages, the diagnosis of gynecological diseases. Results. Summarizing obtained in this study results one should stress the positive long-term effect of applying Mastofemin for the treatment of proliferative changes of the breast in women of reproductive age. This is manifested by a decrease in the intensity of clinical signs of mastitis, consistent with the results of sonographic control. Established positive dynamics in the treatment of cystic mastitis, dectective and when combined cystic mastopathy with dectective. In the control group of patients for a given observation period (6 months) no significant changes in clinical signs of mastitis and sonographic characteristics. Regression of disease has not occurred in any of the patients, in 2 patients increased sensitivity of the breast after 6 months moved to the soreness. Sonographic characteristics of mastitis during the observation period did not change. Thus, the use of Mastofemin aimed at pathogenetic treatment of mastitis and prevention of breast cancer. Conclusion. Application of Mastofemin during the treatment of mastitis in women of reproductive age significantly improves the clinical condition of patients; reduce the subjective and objective symptoms of the disease. The positive effect of the treatment with Mastofemin proved in the case of the treatment of sonographic following forms of mastitis: cystic mastopathy, cystic mastopathy with dectectasy. Mastofemin may be the drug of choice for complex conservative monotherapy in women of reproductive age with proliferative changes in the breast, and can also be used as part of complex treatment in patients with diffuse changes of the breast when combined with hyperplastic processes of the myometrium and endometrium. Keywords: mastopathy, breast gland, herbal medicine, herbal remedies, Mastofemin.

Download Full-text