Role Of Monoaminergic Systems Research Articles

THE ROLE OF THE EPIPHYSIS HORMONE IN THE DEVELOPMENT OF EPILEPTIC SEIZURES IN YOUNG MEN

This article discusses the role of monoaminergic systems, namely the role of the pineal gland hormone in the pathogenesis of epilepsy. The functions of melatonin in this pathology in young men are also considered.

Antidepressant-like effect of hydroalcoholic extract from barks of Rapanea ferruginea: Role of monoaminergic system and effect of its isolated compounds myrsinoic acid A and B

Major Depressive Disorder (MDD) is a highly disabling condition and has been linked to increased inflammatory mediators. Hydroalcoholic extract from barks of Rapanea ferruginea (HEBRF) and the majoritary compounds—myrsinoic acid A (MAA) and B (MAB)—have been studied due to their anti-inflammatory potential, but there is no evidence about its antidepressant-like effects. This research investigated the HEBRF, MAA, and MAB antidepressant-like effect, besides the involvement of the monoaminergic system and MAO-A activity in the HEBRF antidepressant-like effect. HEBRF (50−300 mg/kg, p.o.), MAA (5−30 mg/kg, p.o.) or MAB (3−60 mg/kg, p.o.) were administrated to mice, and behavioral parameters were assessed using the tail suspension test (TST), splash test (ST) and open field test (OFT). The involvement of monoaminergic system in the HEBRF antidepressant-like effect was established through the pretreatment of mice with antagonists. The influence triggered by HEBRF in the monoamine oxidase A (MAO-A) activity was evaluated in the hippocampus (HIP) and prefrontal cortex (PFC) of mice. HEBRF (100−300 mg/kg) promoted antidepressant-like effect in the TST and augmented the total time of grooming in the ST, without compromising the locomotor activity. Pretreatment of mice with serotoninergic, dopaminergic, and noradrenergic antagonists, reversed the HEBRF antidepressant-like effect. Besides, HEBRF inhibited the MAO-A activity in the HIP and PFC. Moreover, MAA (5 mg/kg) and MAB (3 mg/kg) also promoted antidepressant-like and anti-anhedonic effects in mice. Data showed that monoaminergic system is involved in the HEBRF antidepressant-like effect, besides MAA and MAB possibly could be responsible for these pharmacological effects.

Role of Monoaminergic Systems of the CNS in Different Periods after Status Epilepticus and Its Relation to Cerebral Hemodynamics.

Changes in the monoaminergic mechanisms in the brain at different terms after status epilepticus are determined by diverse causes and depend on the role of monoamines in the implementation of specific postictal rearrangements in CNS. Two mutually aggravating pathways cause disorders of monoaminergic mechanisms in the brain in 24 h after epileptic status: high spike-wave activity accompanied by hypocirculation that form a vicious circle; the resulting deficiency of monoamine consolidates the self-sustaining epileptic circuit. Increased activity of monoaminergic mechanisms in 5 days after epileptic status is a result of compensatory-restorative reorganization of neuronal networks and is not accompanied by spike-wave activity and hemodynamics disorders, but high convulsive readiness persists. Disturbances of monoaminergic mechanisms in 30 days after epileptic status prolong convulsive readiness that can serve as a pathogenetic basis for delayed cerebral disorders.

Role of monoaminergic systems and ambient temperature in bath salts constituent 3,4-methylenedioxypyrovalerone (MDPV)-elicited hyperthermia and locomotor stimulation in mice

3,4-Methylenedioxypyrovalerone (MDPV) is a common constituent of illicit bath salts products, and in vitro studies implicate monoamine transporters as mediators of its pharmacological effects. Locomotor and thermoregulatory effects of MDPV depend on ambient temperature, so the current studies aimed to gauge the involvement of dopamine (DA), norepinephrine (NE), and serotonin (5-HT) in MDPV-induced locomotor stimulation and hyperthermia in the mouse at different ambient temperatures. Mice were pretreated with the selective 5-HT-reuptake inhibitor fluoxetine (3 mg/kg), the NE-reuptake inhibitor desipramine (3 mg/kg), the DA-reuptake inhibitor bupropion (10 mg/kg), or saline, followed by 10 mg/kg MDPV while thermoregulation and locomotor activity were monitored via radiotelemetry. In other studies, mice were pretreated for three days with saline, 100 mg/kg of the tryptophan hydroxylase inhibitor para-chlorophenylalanine (p-CPA), or 100 mg/kg of the tyrosine hydroxylase inhibitor α-methyl-para-tyrosine (α-MPT) before receiving 10 mg/kg MDPV on the fourth day. All manipulations were conducted at both 20 °C and 28 °C ambient temperatures. MDPV increased locomotor activity under both ambient conditions and modestly increased core body temperature at 20 °C; however, neither pretreatment with monoamine reuptake inhibitors nor monoamine synthesis inhibitors significantly altered these effects. At 28 °C, MDPV induced a more pronounced hyperthermic effect which was attenuated by bupropion, desipramine, or fluoxetine pretreatment, but not by the monoamine synthesis inhibitors. These results suggest that MDPV may have a more complex pharmacological profile than suggested by in vitro studies, perhaps extending beyond interactions with monoamine transporters. A more thorough binding profile of MDPV at various brain recognition sites should be developed.This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’

Antidepressant-like activity of methyl jasmonate involves modulation of monoaminergic pathways in mice

PurposeThe efficacy of current antidepressant drugs has been compromised by adverse effects, low remission and delay onset of action necessitating the search for alternative agents. Methyl jasmonate (MJ), a bioactive compound isolated from Jasminum grandiflorum has been shown to demonstrate antidepressant activity but its mechanism of action remains unknown. Thus, the role of monoaminergic systems in the antidepression-like activity of MJ was investigated in this study. Materials and methodsMice were given i.p. injection of MJ (5, 10 and 20mg/kg), imipramine (10mg/kg) and vehicle (10mL/kg) 30min before the forced swim test (FST) and tail suspension test (TST) were carried out. The involvement of monoaminergic systems in the anti-depressant-like effect of MJ (20mg/kg) was evaluated using p-chlorophenylalanine (pCPA), metergoline, yohimbine, prazosin, sulpiride and haloperidol in the TST. ResultsMJ significantly decrease the duration of immobility in the FST and TST relative to control suggesting antidepressant-like property. However, pretreatment with yohimbine (1mg/kg, i.p., an α2-adrenergic receptor antagonist) or prazosin (62.5μg/kg, i.p., an α1-adrenoceptor antagonist) attenuated the antidepressant-like activity of MJ. Also, pCPA; an inhibitor of serotonin biosynthesis (100mg/kg, i.p) or metergoline (4mg/kg, i.p., 5-HT2 receptor antagonist) reversed the anti-immobility effect of MJ. Sulpiride (50mg/kg, i.p., a D2 receptor antagonist) or haloperidol (0.2mg/kg, i.p., a dopamine receptor antagonist) reversed the anti-immobility effect of MJ. ConclusionThe results of this study suggest that serotonergic, noradrenergic and dopaminergic systems may play a role in the antidepressant-like activity of MJ.

Agmatine enhances antidepressant potency of MK-801 and conventional antidepressants in mice

Agmatine, an endogenous guanidine amine, has been shown to produce antidepressant-like effects in animal studies. This study investigated the effects of the combined administration of agmatine with either conventional monoaminergic antidepressants or the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 in the tail suspension test (TST) in mice. The aim was to evaluate the extent of the antidepressant synergism by examining the ability of a fixed dose of agmatine to shift the antidepressant potency of fluoxetine, imipramine, bupropion and MK-801. A sub-effective dose of agmatine (0.0001mg/kg, p.o.) significantly increased the potency by which fluoxetine, imipramine, bupropion and MK-801 decreased immobility time in the TST by 2-fold (fluoxetine), 10-fold (imipramine and bupropion) and 100-fold (MK-801). Combined with previous evidence indicating a role of monoaminergic systems in the effect of agmatine, the current data suggest that agmatine may modulate monoaminergic neurotransmission and augment the activity of conventional antidepressants. Moreover, this study found that agmatine substantially augmented the antidepressant-like effect of MK-801, reinforcing the notion that this compound modulates NMDA receptor activation. These preclinical data may stimulate future clinical studies testing the effects of augmentation therapy with agmatine for the management of depressive disorders.

Role of Monoaminergic System in the Etiology of Olive Oil Induced Antidepressant and Anxiolytic Effects in Rats

Olive oil is the major component of the Mediterranean diet and has rich history of nutritional and medicinal uses. In the present study, the antidepressant and anxiolytic effects and their neurochemical basis following repeated administration of extravirgin olive oil were monitored. Male albino Wistar rats were used during study. Animals of test group were given olive oil orally at the dose of 0.25 mL/kg daily for 4 weeks. Control rats received equal volume of water. Elevated-plus maze (EPM) test and forced swim test (FST) were performed for the assessment of anxiety and depression like symptoms. An increase in time spent in open arm in EPM and increased struggling time in FST following long-term administration of olive oil indicate that olive oil has anxiolytic and antidepressant properties. Neurochemical results showed that repeated administration of olive oil decreased the levels of brain 5-HT (5-hydroxytryptamine), 5-HIAA (5-hydroxyindoleacetic acid), and levels of DA (dopamine); however, levels of DA metabolite HVA (homovalinic acid) were increased. Hence, present findings suggest that olive oil has neuroprotective effects. It reduces behavioral deficits via altering 5-HT and DA metabolism. So it could be used as a therapeutic substance for the treatment of depression and anxiety.

Benzo[α]pyrene‐Induced Anti‐Depressive‐like Behaviour in Adult Female Mice: Role of Monoaminergic Systems

Benzo[α]pyrene (B[α]P) is a ubiquitous environmental pollutant exhibiting adverse effects on cognitive function and behaviour. In this study, depressive or antidepressive effects of B[α]P were investigated. Here, we report that a subacute B[α]P oral exposure (0.02-0.2 mg/kg) increases mobility behaviour in female adult mice in the tail suspension test, but not in the forced swimming test, without altering locomotion, suggesting that the tail suspension test was a more sensitive indicator of B[α]P-induced neurobehavioural disturbance. This might be because of differences in neurochemical substrates and pathways, mediating the performance in these behavioural models of depression. The effect of B[α]P on female adult mice in the tail suspension test was similar to that obtained with subacute treatment of the antidepressant reference drug imipramine (10 mg/kg). Therefore, B[α]P at 0.02 mg/kg and 0.2 mg/kg induces an antidepressant-like effect in mice, suggesting a neurobehavioural disturbance after oral exposure to this environmental compound. Furthermore, oral exposure to B[α]P at 0.02 mg/kg significantly increased gene expression levels of the brain receptors 5-hydroxytryptamine (serotonin) 1A (5HT(1A)) and alpha-1D adrenergic (ADRA(1D)). In summary, the presented findings suggest that subacute oral exposure to B[α]P results in behavioural changes in female adult mice, possibly caused by alterations in the serotoninergic and adrenergic systems.

Dissociative experiences in obsessive-compulsive disorder and trichotillomania: Clinical and genetic findings

A link between dissociation proneness in adulthood and self-reports of childhood traumatic events (including familial loss in childhood, sexual/physical abuse and neglect) has been documented. Several studies have also provided evidence for an association between dissociative experiences and trauma in patients with various psychiatric disorders, including post-traumatic stress disorder, borderline personality, dissociative identity and eating disorders. Based on the relative paucity of data on dissociation and trauma in obsessive-compulsive disorder (OCD) and trichotillomania (TTM), the primary objective of this study was to examine the relationship between trauma and dissociative experiences (DE) in these two diagnostic groups. Furthermore, the availability of clinical and genetic data on this sample allowed us to explore clinical and genetic factors relevant to this association. A total of 110 OCD and 32 TTM patients were compared with respect to the degree of dissociation (using the Dissociative Experiences Scale [DES]) and childhood trauma (using the Childhood Trauma Questionnaire [CTQ]). Patients were classified on the DES as either “high” (mean DES score ≥ 30) or “low” (mean DES score < 30) dissociators. Additional clinical and genetic factors were also explored with chi-square and t tests as appropriate. A total of 15.8% of OCD patients and 18.8% of TTM patients were high dissociators. OCD and TTM groups were comparable on DES and CTQ total scores, and in both OCD and TTM groups, significant positive correlations were found between mean DES scores and mean CTQ subscores of emotional abuse, physical abuse, sexual abuse, and physical neglect. In the OCD group, high dissociators were significantly younger than low dissociators, and significantly more high dissociators than low dissociators reported a lifetime (current and past) history of tics ( P < .001), Tourette’s syndrome ( P = .019), bulimia nervosa ( P = .003), and borderline personality disorder ( P = .027). In the TTM group, significantly more high dissociators than low dissociators reported (lifetime) kleptomania ( P = .005) and depersonalisation disorder ( P = .005). In the Caucasian OCD patients (n = 114), investigation of genetic polymorphisms involved in monoamine function revealed no significant differences between high and low dissociator groups. This study demonstrates a link between childhood trauma and DE in patients with OCD and TTM. High dissociative symptomatology may be present in a substantial proportion of patients diagnosed with these disorders. High dissociators may also be differentiated from low dissociators on some demographic features (e.g., lower age) and comorbidity profile (e.g., increased incidence of impulse dyscontrol disorders). Additional work is necessary before conclusions about the role of monoaminergic systems in mediating such dissociation can be drawn.

The role of monoaminergic systems in central IL‐1β‐induced changes in intestinal motility

Abstract Intracerebroventricular (i.c.v.) injection of interleukin‐1β (IL‐1β) in fed rats induces stimulation of caecocolonic contractions, involving corticotropin‐releasing factor (CRF) and the reappearance of the fasted motor pattern (presence of migrating myoelectric complexes, MMCs) at the small intestinal level, which is mediated by prostaglandins (PGs). The mechanisms of these effects were further investigated by focusing on the possible involvement of central monoaminergic systems. Motility was appraised in conscious rats chronically implanted with electrodes in the jejunum and caecum, and a catheter in a lateral ventricle of the brain. IL‐1β (15 ng, i.c.v.) was administered in fed rats that were untreated, or after previous administration of either antagonists of α1 and α2 adrenergic (prazocin and yohimbine), D1 and D2 dopaminergic (SCH 23390 and sulpiride) and 5HT3 serotonergic (granisetron) receptors. Only prazocin and yohimbine (1 mg kg−1 i.p.) significantly reduced the duration of the MMC pattern induced by IL‐1β at the jejunal level (78 ± 35 min and 40 ± 12 min, respectively, vs 223 ± 48 min in control studies). In contrast, the caecal stimulation triggered by IL‐1β was not only blocked by prazocin and yohimbine (1 mg kg−1 i.p.), but also by sulpiride (1 mg kg−1 i.p.) and granisetron (1 mg kg−1 i.p.). This study confirms that IL‐1‐induced changes in small and large intestinal motility are expressed through two separate pathways. We can suggest that mediators acting to modulate CRF release, such as catecholamines through α1 and α2 receptors, dopamine through D2 receptors, and serotonin through 5HT3 receptors, could be involved in the caecal stimulation. PG‐dependent changes in the jejunal motility pattern seem to be linked to activation of α adrenoceptors.

Changes in balance of biogenic monoamines and their metabolites in rats with hyperbaric epilepsy

A protective role of monoamine oxidase inhibitors in hyperbaric epilepsy has been reported [2], confirming involvement of the brain monoaminergic systems in the development of seizure activity. However, changes in the balance of monoamines and their metabolites in different phases of the epileptiform seizure have not yet been studied~ Moreover, there are virtually no data on the role of monoaminergic systems of the heart in the genesis of oxygen poisoning. The aim of this investigation was to study changes in concentrations of biogenic amines and their metabolites in certain parts of the brain and heart of rats exposed to a session of toxic hyperbaric oxygenation of varied duration. EXPERIMENTAL METHOD Biogenic amines and their metabolites were determined by high-performance liquid chromatography (HPLC) with electrochemical detection [4]. The convulsive form of oxygen poisoning was induced by exposing noninbred male albino rats in a pressure chamber to oxygen in a pressure of 6 atm for 5-60 min. Periods of compression and decompression each lasted 20 min. At the end of decompression the rats were decapitated and brain and heart structures were removed in the cold and kept in liquid nitrogen until use. EXPERIMENTAL RESULTS Three stages of hyperbaric epileptic fit were investigated: compensatory (exposure for 5 min), convulsive (exposure 27 min), and terminal (exposure 60 min). The results are given in Tables I and 2. It will be Clear from Tables 1 and 2 that under normal circumstances the concentration of catecholamine (CA) metabolites in the rat heart was much lower than in the brain: in the left and right ventricles homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DHPAA) were absent; no 3-methoxy-4-hydroxyphenylglycol (MHPEG) could be found and the 5-hydroxyindoleacetic acid (5-HIAA) level was very low. Compared with the left ventricle, the right contained more 3,4-dihydroxyphenylglycol (DHPEG), noradrenalin (NA), and adrenalin (A), but less dihydroxyphenylalanine (DOPA). No metabolites of dopamine (DA) were present in the ventricles of the heart, but its precursor (DOPA) was present. No 3,4-dihydroxymandelic acid (DHMA) was found in the atria (total preparation), but concentrations of serotonin (5-HT) and 5-HIAAwere significantly higher than in the ventricles; metabolites of DA, and also MHPEG, were absent but the DOPA concentration was lower than in the left ventricle but higher than in the right. In the septum of the heart concentrations of NA and A were much lower than in the ventricles and atria; neither DHMA nor HVA was found, but DHPAA was present in higher concentrations that in other parts of the heart, but the 5-HIAA concentration was very low. The results showing the distribution of monoamines and their metabolites in the normal rat brain and heart justify the conclusion that the principal monoaminergic substances in the rat heart are NA and A, and that virtually all the monoamines and their metabolites studied are well represented in the brain.

Neuropharmacology of cocaine: role of monoaminergic systems.

Neuropharmacology of cocaine: role of monoaminergic systems.

Role of monoaminergic systems in morphine-induced respiratory depression

The respiratory response to morphine sulfate was assessed in rats pretreated with different modifiers of noradrenergic and serotonergic activity and, additionally, the respiratory depression was related to the brain levels of the two amines, serotonin (5-HT) and norepinephrine (NE). At respiratory depressant doses, morphine induced an increase in 5-HT and a decrease in NE levels in the medullapons area. The time sequence of respiratory depression correlated with a decline in NE and a rise in 5-HT levels. Pretreatments which increased 5-HT levels potentiated the respiratory depression and agents which increased NE levels antagonized the depression. A system of antagonistic modulation by the two amines of morphine-induced respiratory depression is proposed, whereby 5-HT functions as a depressant mediator and NE as an excitatory mediator. Naloxone appears to reverse the respiratory depression by altering the serotonergic component of the action of morphine.