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1.
Chaos ; 30(9): 093136, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33003924

ABSTRACT

We consider a generic interaction-redistribution model of vegetation dynamics to investigate the formation of patchy vegetation in semi-arid and arid landscapes. First, we perform a weakly nonlinear analysis in the neighborhood of the symmetry-breaking instability. Following this analysis, we construct the bifurcation diagram of the biomass density. The weakly nonlinear analysis allows us to establish the condition under which the transition from super- to subcritical symmetry-breaking instability takes place. Second, we generate a random distribution of localized patches of vegetation numerically. This behavior occurs in regimes where a bare state coexists with a uniform biomass density. Field observations allow to estimate the total biomass density and the range of facilitative and competitive interactions.


Subject(s)
Ecosystem , Models, Biological , Biomass
2.
Philos Trans A Math Phys Eng Sci ; 376(2135)2018 Nov 12.
Article in English | MEDLINE | ID: mdl-30420548

ABSTRACT

We report for the first time on the formation of spirals like vegetation patterns in isotropic and uniform environmental conditions. The vegetation spirals are not waves and they do not rotate. They belong to the class of dissipative structures found out of equilibrium. Isolated or interacting spirals and arcs observed in South America (Bolivia) and North Africa (Morocco) are interpreted as a result of curvature instability that affects the circular shape of localized patches. The biomass exhibits a dynamical behaviour with arcs that transform into spirals. Interpretation of observations and of the predictions provided by the theory is illustrated by recent measurements of peculiar plant morphology (the alfa plant, or Stipa tenacissima L.) originated from northwestern Africa and the southern part of the Iberian Peninsula.This article is part of the theme issue 'Dissipative structures in matter out of equilibrium: from chemistry, photonics and biology (part 2)'.

3.
Ann Pharm Fr ; 72(3): 164-77, 2014 May.
Article in English | MEDLINE | ID: mdl-24780832

ABSTRACT

INTRODUCTION: Psychotimulant-antipyschotic combinations are frequently used in child psychiatry, but have been rarely described in the literature. METHOD AND PATIENTS: We propose here a retrospective study of 44 children who received the combination methylphenidate (MPH)-risperidone (RIS). The sample is composed of children who received either MPH (n=28) or RIS (n=16) as primary treatment. A vast majority of the children had a comorbid attention deficit hyperactivity disorder (ADHD) diagnosis. RESULTS: For over 60% of patients, regardless of their initial monotherapy, bitherapy decreased the symptoms of ADHD and conduct disorder, sleep disorders and anxiety. Concerning the safety of the bitherapy, a compensation effect on weight gain and appetite was respectively observed in 70% and 50% of patients. Even though iatrogenic tachycardia can be encountered with both drugs, it has never been reported when they are associated and we have reported a total of 3 cases in our study. We have also observed a case of dyskinesia resolved with the discontinuation of the treatment. DISCUSSION/CONCLUSION: MPH-RIS bitherapy appears to be particularly effective in ADHD with conduct disorder symptoms. Although tolerance may limit its use, the benefit/risk ratio seems favourable for a number of children.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Child Psychiatry , Methylphenidate/therapeutic use , Risperidone/therapeutic use , Adolescent , Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/psychology , Child , Conduct Disorder/drug therapy , Conduct Disorder/psychology , Drug Combinations , Female , Follow-Up Studies , Humans , Male , Methylphenidate/administration & dosage , Methylphenidate/adverse effects , Retrospective Studies , Risperidone/administration & dosage , Risperidone/adverse effects , Treatment Outcome
4.
Behav Brain Res ; 261: 8-16, 2014 Mar 15.
Article in English | MEDLINE | ID: mdl-24333542

ABSTRACT

Methyl donor deficiencies and chronic stress cause depression independently, but their interaction has never been thoroughly evaluated. In our study, methyl donor deficient diet and chronic stress condition consisted respectively of a B2, B9, B12, and choline-free diet and a chronic mild stress procedure. Rats were randomly assigned to six groups with three "diet" conditions (free-feeding, pair-fed and methyl donor deficient diet) and two "stress" conditions (no-stress and stress) and were evaluated in the open-field, the elevated plus-maze and the forced swimming test. After the behavioral evaluation, corticosterone and homocysteine plasma levels were measured and dopamine, DOPAC, serotonin, 5HIAA concentrations were evaluated in several brain areas. Rats given a methyl donor deficient diet for 11 weeks causing elevated plasma homocysteine levels were compared to pair-fed and free-feeding rats with or without unpredictable chronic mild stress. Regardless of stress environmental conditions, the methyl donor deficient diet decreased plasma corticosterone levels and caused disinhibition in the elevated plus-maze condition relative to both control groups. However, stress potentiated the effects of the deficient regimen on rearing in the open-field and climbing in the forced swim test. The dietary changes involved in behavior and plasma corticosterone could be caused by homocysteine-induced decreases in dopamine and 5-hydroxytryptamine metabolites in selective brain regions and it can be noted that regardless of stress-conditions, methyl donor deficient diet decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus and selectively 5HIAA/serotonin ratio in the sensorimotor cortex. Our experimental data is particularly relevant in the context of neuropsychiatric disorders frequently associated with folate deficiency and hyperhomocysteinemia.


Subject(s)
Choline Deficiency/complications , Choline Deficiency/metabolism , Folic Acid Deficiency/complications , Folic Acid Deficiency/metabolism , Stress, Psychological/etiology , Analysis of Variance , Animals , Biogenic Amines/metabolism , Brain/metabolism , Chronic Disease , Corticosterone/blood , Diet , Disease Models, Animal , Exploratory Behavior/physiology , Homocysteine/blood , Maze Learning/physiology , Rats , Rats, Wistar , Spinal Cord/metabolism , Stress, Psychological/blood , Stress, Psychological/pathology , Swimming/psychology
5.
Encephale ; 36(6): 461-71, 2010 Dec.
Article in French | MEDLINE | ID: mdl-21130229

ABSTRACT

RATIONALE AND OBJECTIVES: Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake. It has recently been discovered that bupropion may act as a non-competitive cholinergic nicotinic receptor antagonist, and that it may inhibit the activation of reward systems triggered by nicotine. Buproprion's efficacy as a smoking cessation aid has been demonstrated by numerous clinical trials that have compared its effects with those of placebo and other nicotinic substitutes. In 2001, buproprion SR received marketing authorization in France as a smoking cessation aid, under the name ZYBAN®. Tobacco addiction indeed remains a major public health issue. Among patients with psychiatric conditions, chronic tobacco consumption is frequent. The development of non-nicotinic drugs may therefore enhance therapeutic possibilities. However, the psychotropic effects of these molecules should be taken into account. We have recently reported the case of a patient with schizoaffective disorder, who presented two acute bupropion-induced psychotic episodes. We have also undertaken an exhaustive bibliographical research on this subject. The aim of the present study is to present the information available to us, in order to suggest aetiopathogenic hypotheses and therapeutic proposals. DATA SOURCES: The following databases were consulted on a regular basis, with no date restriction: Medline, Cochrane and Elsevier. The present study identified 22 cases of psychotic conditions associated with buproprion, as well as randomized and pharmacovigilance studies published in English, from December 1985 to November 2008. Since 2002, there have been three published case-reports on patients who underwent a tobacco cessation program. DATA SYNTHESIS: Psychotic disorders associated with buproprion appear after an average of 10 days of 300 mg/d bupropion intake. In about two third of cases, the patients have no history of psychiatric conditions. In one third of cases, they have a history of thymic disorders. In our review, auditory, visual or cenaesthetic hallucinations frequently occur (85% of the reported cases), and are sometimes characterized by single episodes and/or are rationalized. Some of them occur along with delusional episodes (mystical, paranoid, etc.). The patients are restless, confused, but seldom exhibit dissociative and thymic symptoms. DISCUSSION AND CONCLUSIONS: From an aetiopathogenic, clinical and evolutive standpoint, buproprion-induced psychotic episodes share many similarities with acute organic or toxic psychosis (notably induced by amphetamines). The hypothesis of a dopaminergic hyper-reactivity should be analyzed. Moreover, most of these patients were taking other medication, and the possibility of a dopaminergic potentialization prior to buproprion intake could be suggested. In such cases, bupropion should be discontinued and complete remission is expected within an average of 10 days. Even though neuroleptic drugs are still frequently used in these cases, benzodiazepines could become a valid alternative, according to the model of amphetamine-induced acute psychosis.


Subject(s)
Antidepressive Agents, Second-Generation/toxicity , Bupropion/toxicity , Psychoses, Substance-Induced/etiology , Smoking Cessation , Antidepressive Agents, Second-Generation/therapeutic use , Bupropion/therapeutic use , Humans , Psychoses, Substance-Induced/diagnosis , Psychoses, Substance-Induced/psychology , Risk Factors , Smoking Cessation/psychology
6.
J Physiol Pharmacol ; 61(4): 483-90, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20814077

ABSTRACT

Human opiorphin QRFSR-peptide protects enkephalins from degradation by human neutral endopeptidase (hNEP) and aminopeptidase-N (hAP-N) and inhibits pain perception in a behavioral model of mechanical acute pain (1). Here, using two other pain rat models, the tail-flick and the formalin tests, we assess the potency and duration of the antinociceptive action of opiorphin with reference to morphine. The occurrence of adverse effects with emphasis on the side-effect profile at equi-analgesic doses was compared. We demonstrate that opiorphin elicits minimal adverse morphine-associated effects, at doses (1-2 mg/kg, i.v.) that produce a comparable analgesic potency in both spinally controlled thermal-induced acute and peripheral chemical-induced tonic nociception. The analgesic response induced by opiorphin in the formalin-induced pain model preferentially requires activation of endogenous mu-opioid pathways. However, in contrast to exogenous mu-opioid agonists such as morphine, opiorphin, does not develop significant abuse liability or antinociceptive drug tolerance after subchronic treatment. In addition, anti-peristaltism was not observed. We conclude that opiorphin, by inhibiting the destruction of endogenous enkephalins, which are released according to the painful stimulus, activates restricted opioid pathways specifically involved in pain control, thus contributing to a greater balance between analgesia and side-effects than found with morphine. Therefore, opiorphin could give rise to new analgesics endowed with potencies similar to morphine but with fewer adverse effects than opioid agonists. Its chemical optimization, to generate functional derivatives endowed with better bioavailability properties than the native peptide, could lead to a potent class of physiological type analgesics.


Subject(s)
Analgesics, Opioid/administration & dosage , Behavior, Addictive , Drug Tolerance/physiology , Oligopeptides/administration & dosage , Pain Measurement/drug effects , Salivary Proteins and Peptides/administration & dosage , Analgesics, Opioid/adverse effects , Animals , Behavior, Addictive/chemically induced , Dose-Response Relationship, Drug , Humans , Male , Oligopeptides/adverse effects , Pain Measurement/methods , Rats , Rats, Wistar , Salivary Proteins and Peptides/adverse effects
7.
J Physiol Pharmacol ; 61(3): 355-62, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20610867

ABSTRACT

Human opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase-N and inhibits pain perception in various behavioral rodent models of pain via endogenous enkephalin-related activation of opioidergic pathways. In addition to pain control, endogenous opioid pathways are also implicated in the modulation of emotion-related behaviors. Thus, we explored the dose-dependent motivational responses induced by opiorphin using the forced swim test, the standard rat model of depression. In addition, to further understand the endogenous events triggered by opiorphin, we investigated the specific involvement of mu- or delta-opioid receptor-dependent pathways. In parallel, the locomotor activity test was used to detect possible sedation or hyperactivity. Here, we report for the first time that at 1-2 mg/kg i.v. doses, opiorphin elicited antidepressant-like effects by activating endogenous delta-opioidergic pathways, since that activation was reversed by the selective delta-opioid antagonist naldrindole (10 mg/kg i.p.). The antidepressive behavioral responses exerted by opiorphin are specific at systemically active doses. Treated-rats did not develop either hypo- or hyper-active responses in a locomotor test or amnesic behavioral response in the passive avoidance rat model. In addition, opiorphin did not induce either anxiolytic-, or anxiogenic-like responses in the conditioned defensive burying test. Taking the data together, we conclude that opiorphin is able to elicit antidepressant-like effects, mediated via delta-opioid receptor-dependent pathways, by modulating the concentrations of endogenous enkephalin released in response to specific physical and/or psychological stimuli. Thus, opiorphin or optimized derivatives is a promising single candidate to treat disorders that include both pain and mood disorders, particularly depression.


Subject(s)
Antidepressive Agents/metabolism , Antidepressive Agents/pharmacology , Enkephalins/metabolism , Oligopeptides/metabolism , Oligopeptides/pharmacology , Opioid Peptides/metabolism , Receptors, Opioid, delta/metabolism , Salivary Proteins and Peptides/metabolism , Salivary Proteins and Peptides/pharmacology , Analgesics, Opioid/metabolism , Analgesics, Opioid/pharmacology , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Humans , Locomotion/drug effects , Male , Memory Disorders/chemically induced , Motor Activity/drug effects , Opioid Peptides/genetics , Pain Measurement , Rats
8.
Dement Geriatr Cogn Disord ; 28(1): 36-46, 2009.
Article in English | MEDLINE | ID: mdl-19628939

ABSTRACT

BACKGROUND/AIMS: Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer's disease. A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique. The aim of this controlled, randomised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia. METHODS: This was a single-centre, comparative, controlled, randomised study, with blinded assessment of its results. The duration of follow-up was 24 weeks. The treated group (n = 15) participated in weekly sessions of individual, receptive music therapy. The musical style of the session was chosen by the patient. The validated 'U' technique was employed. The control group (n = 15) participated under the same conditions in reading sessions. The principal endpoint, measured at weeks 1, 4, 8, 16 and 24, was the level of anxiety (Hamilton Scale). Changes in the depression score (Geriatric Depression Scale) were also analyzed as a secondary endpoint. RESULTS: Significant improvements in anxiety (p < 0.01) and depression (p < 0.01) were observed in the music therapy group as from week 4 and until week 16. The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 (p < 0.01). CONCLUSION: These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer's disease. This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer's disease.


Subject(s)
Alzheimer Disease/complications , Anxiety/etiology , Anxiety/therapy , Depression/etiology , Depression/therapy , Music Therapy , Aged , Aged, 80 and over , Alzheimer Disease/psychology , Anxiety/psychology , Cognition/physiology , Depression/psychology , Endpoint Determination , Female , Follow-Up Studies , Humans , Male , Neuropsychological Tests , Psychiatric Status Rating Scales , Psychotropic Drugs/therapeutic use , Sample Size
9.
J Food Sci ; 72(3): S203-6, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17995815

ABSTRACT

The preventive effects of ACTICOA powder (AP), a cocoa polyphenolic extract, on free radicals produced by leucocytes in rats after heat exposure (HE) and its protective effects on subsequent cognitive impairments were assessed. AP or vitamin E, the antioxidant reference, was orally administered to rats for 14 d before HE at 40 degrees C temperature during 2 h. The day after HE, free radical production by leucocytes in rats treated with AP or vitamin E was significantly reduced as compared to control. Unlike controls, AP- and vitamin E-treated rats discriminated between active lever and inactive levers in a light extinction paradigm. In the Morris water maze, escape latencies before reaching the hidden platform by AP- and vitamin E-treated rats decreased throughout testing. The daily oral administration of AP or vitamin E protected rats from cognitive impairments after HE by counteracting the overproduction of free radicals.


Subject(s)
Antioxidants/pharmacology , Cacao/chemistry , Cognition/drug effects , Free Radicals/metabolism , Hot Temperature , Leukocytes/drug effects , Administration, Oral , Animals , Cognition/physiology , Flavonoids , Leukocytes/metabolism , Male , Phenols , Polyphenols , Random Allocation , Rats , Rats, Wistar , Vitamin E/pharmacology
10.
Spectrochim Acta A Mol Biomol Spectrosc ; 62(4-5): 875-9, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16099707

ABSTRACT

Room temperature UV-vis absorption spectra of the tautomeric system 3,5-dithio-2,7-dimethyl-[1,2,4]-triazepine in solution, in acetonitrile (CH3CN), are measured at different water volume percentages. The comparison of the obtained measures to the calculated allowed absorption transitions, using ZINDO/S package, reveals the coexistence of all the tautomeric forms in aprotic polar solution with a high dominance of the dithione form. The solute-water hydrogen bond, which seems to be of 1:n-type, favours the dithiol and monothiol conformers to the detriment of the dithione one. Further experimental investigations lead to the result that standing at ambient Laboratory conditions in the dark favours the dithione tautomeric isomer, while standing at indirect sunlight shifts the tautomeric equilibrium away from this species.


Subject(s)
Azepines/chemistry , Acetonitriles , Azepines/radiation effects , Darkness , Isomerism , Light , Solvents/chemistry , Spectrophotometry, Ultraviolet , Temperature , Water/chemistry
11.
Radiat Prot Dosimetry ; 116(1-4 Pt 2): 290-2, 2005.
Article in English | MEDLINE | ID: mdl-16604646

ABSTRACT

A three-dimensional neutronic modelling of the LMJ facility has been performed. The Monte Carlo transport code TRIPOLI is used to obtain the neutron spectra required for the inventory code FISPACT. Nodal activation responses and time-dependent decay gamma spectra are produced and used as source terms for further treatment by TRIPOLI for a range of engineering and safety assessments. It is shown that three-dimensional neutronic and nodal activation can be performed in a convenient way and the results obtained by this procedure will serve as a data-base for design and S&E analysis.


Subject(s)
Gamma Rays , Lasers , Models, Biological , Neutrons , Occupational Exposure/analysis , Radiation Monitoring/methods , Radiation Protection/instrumentation , Body Burden , Computer Simulation , France , Models, Statistical , Monte Carlo Method , Radiation Dosage , Radiation Protection/methods , Relative Biological Effectiveness
12.
Horm Behav ; 46(5): 684-91, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15555512

ABSTRACT

In sexually mature male rats, sialorphin is synthesized under androgenic control and its surge endocrine secretion is evoked in response to environmental acute stress. These findings led us to suggest that this signaling mediator might play a role in physiological and behavioral integration, especially reproduction. The present study investigates the effects induced by sialorphin on the male sexual behavior pattern. Intact male rats were treated in acute mode, with sialorphin at the 0.3, 1, and 3 microg/kg doses, before being paired with receptive female for 45 min. The data obtained show that sialorphin increased, in a dose-related manner, the occurrence of intromissions across the successive ejaculatory sequences. The rats treated with the highest 3 microg/kg dose significantly ejaculated less often compared to controls; however, 80% of them achieved up to three ejaculations. Further analyses of mount bouts for rats achieving three ejaculations reveal that there were significant stimulatory effects of sialorphin, at all doses, on the frequency of intromissions before ejaculation and on the propensity of males to engage in investigatory behavior directed to the female during the post-ejaculatory interval. Thus, sialorphin has the ability to modulate, at doses related to physiological circulating levels, the male rat mating pattern, that is, exerting a dual facilitative or inhibitory dose-dependent effect on the sexual performance, while stimulating the apparent sexual arousal or motivation. These findings led us to speculate that the endogenous androgen-regulated sialorphin helps modulate the adaptative balance between excitatory and inhibitory mechanisms serving appropriate male rat sexual response, depending on the context.


Subject(s)
Protein Precursors/physiology , Salivary Proteins and Peptides/physiology , Sexual Behavior, Animal/physiology , Testosterone/physiology , Animals , Female , Male , Random Allocation , Rats , Rats, Wistar , Sex Factors , Submandibular Gland/physiology
13.
Radiat Prot Dosimetry ; 108(3): 247-53, 2004.
Article in English | MEDLINE | ID: mdl-15031446

ABSTRACT

This paper presents the results obtained in a comparison of three neutron spectrum unfolding procedures based on the SAND, MINCHI and UNFANA computer programs. The calculations were performed with data obtained previously from measurements using the PTB Bonner sphere spectrometer and taken from the literature; the neutron dosimetry was done with the Leake rem-meter. The evaluation of some spectrum hardness quantifiers is also reported. The codes give comparable neutron spectrum results. Relative to ambient dose equivalent derived from the Bonner sphere system, as a function of the unfolding code used, the Leake calculated readings were typically 1.16 to 1.91 and 1.58 to 2.69 times larger for the environment of a transport cask with spent fuel elements (Clab) and inside the containment building of a pressurised water reactor (Ring-G), respectively, depending on the calibration fields.


Subject(s)
Algorithms , Equipment Failure Analysis/methods , Neutrons , Radiometry/instrumentation , Radiometry/methods , Spectrum Analysis/methods , Calibration/standards , Radiation Dosage , Radiometry/standards , Software
14.
Neuroreport ; 10(5): 1137-41, 1999 Apr 06.
Article in English | MEDLINE | ID: mdl-10321498

ABSTRACT

A new rat model was established up to evaluate the antinociceptive effect of compounds in visceral pain. The test consisted in measuring the performance of rats in an aversive light stimulus avoidance experimental device. Rats with TNBS-induced colitis had a lower number of total active lever pressings and did not discriminate the active lever from the inactive one. Morphine (1 mg/kg, s.c.) and CI-977 (0.001 mg/kg, s.c.) treatment restored the level of pressing activity of animals and their ability to discriminate the active lever from the inactive one. Naloxone treatment antagonized the improvement of performance produced by morphine. The results obtained indicate that this behavioral paradigm may be used to evaluate the antinociceptive potential of compounds.


Subject(s)
Behavior, Animal/physiology , Colitis/physiopathology , Colitis/psychology , Pain/psychology , Viscera/physiopathology , Analgesics, Opioid/pharmacology , Animals , Behavior, Animal/drug effects , Benzofurans/pharmacology , Cognition/drug effects , Cognition/physiology , Colitis/chemically induced , Colitis/pathology , Colon/drug effects , Colon/pathology , Discrimination, Psychological/drug effects , Discrimination, Psychological/physiology , Male , Morphine/pharmacology , Pyrrolidines/pharmacology , Rats , Rats, Sprague-Dawley , Trinitrobenzenesulfonic Acid/pharmacology
15.
Eur J Pharmacol ; 299(1-3): 17-20, 1996 Mar 28.
Article in English | MEDLINE | ID: mdl-8901002

ABSTRACT

Rats were daily treated for seven days with 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) at a dose of 20 mg/kg/day, i.p. Seven days after treatment withdrawal, the rats were individually tested in a brightly lit apparatus containing two levers: an active lever allowing periods of darkness, and an inactive one. The test was performed over two consecutive days, in 20-min sessions. While control rats had a higher number of total active lever pressings than inactive lever pressings, this was not the case for MPTP-treated rats. Control rats decreased their useless active lever pressings and inactive lever pressings across the two sessions, but MPTP-treated rats did not do either. The absence of the differential effect in rats injected with MPTP may be due to a reduction in reinforcement mechanisms caused by the mild depletion of dopamine in the striatum.


Subject(s)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology , Behavior, Animal/drug effects , Dopamine Agents/pharmacology , Learning/drug effects , 3,4-Dihydroxyphenylacetic Acid/metabolism , Animals , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Dopamine/metabolism , Male , Rats , Rats, Wistar , Substantia Nigra/drug effects , Substantia Nigra/metabolism
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