scholarly journals Interaction of dopamine, nitric oxide and testosterone in the brain system of motivational reinforcement in rats with alcohol dependence and under nitric oxide donator impact

2018 ◽  
Keyword(s):  
Nitric Oxide ◽  
Nucleus Accumbens ◽  
Alcohol Consumption ◽  
Alcohol Dependence ◽  
Alcohol Withdrawal ◽  
Brain Structures ◽  
Male Rats ◽  
Dopamine Level ◽  
Testosterone Concentration ◽  
The Brain

The complex of neurophysiological methods (stereotaxic implantation of electrodes into brain structures, recording of electrical activity of the neocortex, hippocampus, hypothalamus, and nucleus accumbens) was applied to 65 laboratory male rats with models of chronic alcoholization (during 40 days of alcohol consumption in dose 1.25 g/kg body mass) and alcohol withdrawal during 2 days. The leading role of functional changes of electrogenesis in hippocampus, hypothalamus and nucleus accumbens has been revealed in rats being in states of alcohol dependence. The highest absolute spectral powers of oscillations of the β and Ѳ rhythms in the hippocampus and manifestations of generalized hypersynchronous activity with initiation in the hippocampus and hypothalamus were noted in rats under alcohol dependence. The paroxysmal pattern of activity on EEG of the structures of the limbico-neocortical system acquired an “explosive” character after alcohol withdrawal. The complex of neurochemical methods (detection of dopamine and testosterone concentration with enzymoimmunoassay and nitric oxide concentration with spectrophotometric analysis in the brain structures and serum) was carried out after 40 days of alcoholization as well as after 2 days of alcohol withdrawal. Decreased levels of testosterone and nitric oxide were identified in hypothalamus and hippocampus as well as testosterone in nucleus accumbens and serum. There were observed increased dopamine release in nucleus accumbens in response to latest dose of alcohol consumption and recovery of dopamine level after alcohol withdrawal. To the contrary, the dopamine content decreased in hypothalamus in the state of alcohol withdrawal. The five-time (twice a day) intranasal introduction of sodium nitroprusside repaired nitric oxide and testosterone levels in the brain structures of motivational reinforcement and suppressed seizure pattern on EEG but didn’t change testosterone concentration in serum. Obtained data are considered as one of the important aspects of interactions in the system of hormonal-neurotransmitter-metabolic regulatory mechanisms of motivational reinforcement under formation and suppression of alcohol dependence.

scholarly journals Features of neurosteroid support of the state of alcohol dependence and its correction with dosed physical load in rats

2020 ◽  
Vol 11 (4) ◽  
pp. 546-551
Author(s):  
A. M. Titkova ◽  
O. G. Berchenko ◽  
O. V. Veselovska ◽  
A. V. Shliakhova
Keyword(s):  
Alcohol Dependence ◽  
Steroid Hormones ◽  
Alcohol Withdrawal ◽  
Brain Structures ◽  
Physical Load ◽  
Male Rats ◽  
Serum Testosterone Level ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wide Range ◽  
The Brain

The role of steroid hormones in regulation of the functions of the emotiogenic limbic-neocortical system has been actively studied over the recent decades in order to determine their synthesis in the brain structures and role in the development and maintenance of dependence on psychoactive substances. However, the wide range of neurosteroids and their metabolites, as well as structural specific features of the synthesis of both neurohormones and their receptors make it difficult to obtain experimental data and interpret the results of the study. The participation of progesterone, cortisol, testosterone and estradiol in the development of alcohol dependence and the changes in their concentrations in the hypothalamus, hippocampus, amygdala and serum under the influence of dosed physical load were studied in 48 outbred adult male rats. Alcohol dependence was modeled by means of consuming food containing alcohol in the dose of 1.25 g of ethanol per 1 kg of rat body weight for two months. Dosed physical load was reproduced by a rat running in a wheel for 30 minutes daily for 7–10 days against the background of alcohol withdrawal. Neuroethological testing of craving for alcohol, EEG recording of the neocortex, hippocampus and amygdala was performed using a computer-diagnostic complex. The concentration of steroid hormones was determined in the structures of the brain and blood serum by the enzyme-linked immunosorbent assay. It was shown that dosed physical load attenuated the alcohol motivation of rats. On the 5th day it suppressed the electrographic manifestations of paroxysmal activity in the hippocampus and increased the level of the theta-rhythm in the amygdala, and on the 7th day it activated the neocortex with increasing beta-rhythm. This effect was accompanied by an increase in serum testosterone level against the background of maintaining functional tension of the peripheral glucocorticoid link of the hypothalamus-pituitary-adrenal system, which was observed in a state of alcohol dependence. The study demonstrated that progesterone plays the key role in allostatic rearrangements of the functional state of animals. An imbalance of progesterone levels was revealed in the brain structures: an increase – in the hypothalamus and hippocampus, and a decrease – in the amygdala under alcohol dependence; a decrease – in the hippocampus with recovery in the amygdala against the background of its high level in the hypothalamus, which occurs under the influence of dosed physical load on the rats under alcohol withdrawal. Thus, the dosed physical load is a promising approach to alcohol dependence rehabilitation.

Tactile Stimulation in Adult Rats Modulates Dopaminergic Molecular Parameters in the Nucleus Accumbens Preventing Amphetamine Relapse.

2022 ◽  
Author(s):  
Domênika Rubert Rossato ◽  
Higor Zuchetto Rosa ◽  
Jéssica Leandra Oliveira Rosa ◽  
Laura Hautrive Milanesi ◽  
Vinícia Garzella Metz ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Tactile Stimulation ◽  
Male Rats ◽  
Adult Rats ◽  
Delta Fosb ◽  
The Central Nervous System ◽  
Molecular Assessment ◽  
Drug Abstinence ◽  
The Brain ◽  
Abstinence Period

Abstract Amphetamine (AMPH) is a psychostimulant drug frequently related to addiction, which is characterized by functional and molecular changes in the brain reward system, favoring relapse development and pharmacotherapies have shown low effectiveness. Considering the beneficial influences of tactile stimulation (TS) in different diseases that affect the central nervous system (CNS), here we evaluated if TS applied in adult rats could prevent or minimize the AMPH-relapse behavior also accessing molecular neuroadaptations in the Nucleus accumbens (NAc). Following AMPH conditioning in the conditioned place preference (CPP) paradigm, male rats were submitted to TS (15-min session, 3 times a day, for 8 days) during the drug abstinence period, which were re-exposed to the drug in the CPP paradigm for additional 3 days for relapse observation and molecular assessment. Our findings showed that besides AMPH relapse; TS prevented the dopamine transporter (DAT), dopamine 1 receptor (D1R), tyrosine hydroxylase (TH), mu opioid receptor (MOR) increase and AMPH-induced delta FosB (ΔFosB). Based on these outcomes, we propose TS as a useful tool to treat psychostimulant addiction, which subsequent to clinical studies; it could be included in detoxification programs together with pharmacotherapies and psychological treatments already conventionally established.

scholarly journals NEUROPROTECTIVE EFFECT OF SODIUM NITROPRUSSIDE INTRANASAL ADMINISTRATION ON FUNCTIONAL ACTIVITY OF THE BRAIN AND ANXIETY OF RATS WITH ALCOHOL DEPENDENCE

2021 ◽  
pp. 5-13
Author(s):  
Anna Shlіakhova ◽  
Elena Veselovska ◽  
Olga Berchenko ◽  
Anna Titkova ◽  
Elena Prikhodko
Keyword(s):  
Body Weight ◽  
Alcohol Dependence ◽  
Electrical Activity ◽  
Sodium Nitroprusside ◽  
Alcohol Withdrawal ◽  
Baseline Level ◽  
Intranasal Administration ◽  
Alcohol Intake ◽  
Paroxysmal Activity ◽  
The Brain

Introduction. Disturbances of the molecular nitrosergic mechanisms of brain activity regulation underlie the reduction of brain protective functions under alcohol dependence. However, development of pathogenetically substantiated approaches to the correction of nitrogen oxide (NO) imbalance in the structures of the limbico-neocortical system of the brain (LNCSB) remains insufficient. Objective. To study the effect of intranasal sodium nitroprusside (SNP) administration on anxiety, electrical activity of the LNCSB and NO content in the hippocampus, hypothalamus and septum + nucleus аccumbens of rats with alcohol dependence. Materials and methods. The studies were carried out on 50 nonlinear white adult male rats in a chronic experiment in 3 groups: intact rats; rats with alcohol dependence; rats with alcohol dependence and intranasal SNP administration. The model of alcohol dependence was created by voluntary alcohol intake at a dose of 1.25 g/kg body weight of rat for 35 days. SNP was administered intranasal at a dose of 8 μg/kg body weight of the animal. The level of anxiety was determined by means of neuroethological tests: multi-parameter comprehensive assessment of anxiety, «open field» and «tail suspension test». The electrical activity of LNCSB was registered by the stereotactic introduction of electrodes. The concentration of NO was investigated in the hippocampus, hypothalamus, septum + nucleus аccumbens Results. Intranasal administration of SNP to rats with alcohol dependence led to suppression of convulsive and paroxysmal activity, caused by alcoholization and withdrawal of alcohol, on the electroencephalogram of the structures of the LNCSB and increased the absolute power of biopotentials of the delta and theta ranges on the spectrogram of the hippocampus. Reduction of anxiety was found in rats with a high baseline level of anxiety accompanied by recovery of NO level, which was depleted by chronic alcoholization, in the hypothalamus and hippocampus. Conclusions. Intranasal administration of SNP as a NO donor causes anxiolytic effects in the state of alcohol withdrawal depending on the baseline level of anxiety: in rats with the high baseline level of anxiety – reduces this level; in rats with the low baseline level – restrains it at the level of anxiety after alcohol intake. Intranasal administration of SNP to the rats with alcohol withdrawal causes positive changes in the electroencephalogram of the LNCSB, which are manifested in suppression of convulsive and paroxysmal activity and enhancement of brain biopotentials in alpha and delta ranges on spectrogram of hippocampus with sustaining this effect for whole day. Intranasal administration of SNP is a source of short-term supply of NO to brain cells, which leads to the restoration of NO levels in the hypothalamus, hippocampus, septum and nucleus accumbens – structures that are involved in the regulation of emotional motivational behavior. Key words. limbic-neocortical system of the brain, model of alcohol dependence, anxiety, nitric oxide, sodium nitroprusside

Nitric Oxide-Related Agents Alter Alcohol Withdrawal in Male Rats

1995 ◽  
Vol 19 (1) ◽  
pp. 195-199 ◽  
Author(s):  
Michael L Adams ◽  
Bryan N. Sewing ◽  
Jingling Chen ◽  
Edward R. Meyer ◽  
Theodore J. Cicero
Keyword(s):  
Nitric Oxide ◽  
Alcohol Withdrawal ◽  
Male Rats

scholarly journals Effect of acute hypoxia with hypercapnia on the content of monoamines in symmetrical brain structures of the BALB/c male mice

2014 ◽  
Vol 60 (2) ◽  
pp. 258-263 ◽  
Author(s):  
I.V. Karpova ◽  
V.V. Mikheev ◽  
V.V. Marysheva ◽  
E.R. Bychkov ◽  
P.D. Shabanov
Keyword(s):  
Brain Cortex ◽  
Acute Hypoxia ◽  
Brain Structures ◽  
Serotonin Level ◽  
Dopamine Level ◽  
Male Mice ◽  
Left Brain ◽  
Hypoxia With Hypercapnia ◽  
The Right ◽  
The Brain

The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left brain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.

HMGB1gene expression changes in the striatum and amigdal of the rat's brain under alcoholization and ethanol withdrawal

2021 ◽  
Vol 67 (1) ◽  
pp. 95-99
Author(s):  
M.I. Airapetov ◽  
S.O. Eresko ◽  
E.R. Bychkov ◽  
A.A. Lebedev ◽  
P.D. Shabanov
Keyword(s):  
Rat Brain ◽  
Alcohol Withdrawal ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Brain Structures ◽  
Ethanol Withdrawal ◽  
Hmgb1 Protein ◽  
Neuroimmune System ◽  
The Brain

Intracellular signaling mediated by the HMGB1 protein, an agonist of TLRs, is considered as a possible target for the correction of pathologies of the neuroimmune system, however, the expression level of the Hmgb1 gene has not been previously studied in various brain structures of rats exposed to prolonged alcoholization followed by ethanol withdrawal. The study showed that long-term use of ethanol caused to an increase in the level of Hmgb1 mRNA in the striatum of rat brain. Alcohol withdrawal changed the level Hmgb1 mRNA in the striatum and amygdala on the 1st and 14th day. The data obtained may indicate that in different structures of the brain there are multidirectional changes in the molecular mechanisms of the neuroimmune response with prolonged use of ethanol and its withdrawal.

Molecular targets of the ethanol and original anticonvulsant in the treatment of alcohol dependence

2017 ◽  
Vol 41 (S1) ◽  
pp. S350-S350
Author(s):  
T. Shushpanova ◽  
T. Novozheeva ◽  
A. Solonskii ◽  
N. Bokhan ◽  
E. Markova
Keyword(s):  
Immune Response ◽  
Alcohol Dependence ◽  
Open Field ◽  
Chronic Exposure ◽  
Emotional Reactivity ◽  
Benzodiazepine Receptors ◽  
Molecular Targets ◽  
Male Rats ◽  
Experimental Animals ◽  
The Brain

ObjectiveChronic exposure to alcohol causes neuroadaptive changes in the brain, which leads to the recurrence of the disease. Promising in this area is to find new safe and effective pharmacological agents acting on molecular targets of influence of alcohol in the CNS.MethodsExperiments were performed on male rats Wistar and male mice (CBAxC57Bl/6)F1.U. Experimental animals were formed alcohol dependence, based on long-term use of alcohol solution. Animals in a state of alcohol dependence were injected original anticonvulsant meta-chloro-benzhydryl-urea. We evaluated parameters orienting-exploratory behavior and emotional reactivity of the animals in the test “open field”, the cellular and humoral immune response. Properties of benzodiazepine receptors of the brain examined radioreceptor method using selective ligands [3H]flunitrazepam and [3H]Ro5-4864.ResultsChronic exposure to ethanol resulted in a significant change in the parameters of the experimental animal behavior and emotional reactivity in the test “open field”, observed suppression of immune response (∼40%), and increase in the number of receptors on 54.8–59.4% associated with reduced receptor affinity. Administration of meta-chloro-benzhydryl-urea led to the abandonment of the use of ethanol, recorded a correction of the above immunological and behavioral disorders due to alcohol intoxication. Properties of benzodiazepine receptors in the brain of experimental animals receiving the drug at a dose of 100 mg/kg for 14 days, indicators affinity and receptor density were close to the values in the control group.ConclusionsAnticonvulsant has a modulating effect on the functional activity of the nervous and immune systems, reduces compulsive craving for alcohol.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of striatal nitric oxide production on regional cerebral blood flow and seizure development in rats exposed to extreme hyperoxia

2015 ◽  
Vol 119 (11) ◽  
pp. 1282-1288 ◽  
Author(s):  
Heath G. Gasier ◽  
Ivan T. Demchenko ◽  
Barry W. Allen ◽  
Claude A. Piantadosi
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Regional Cerebral Blood Flow ◽  
Brain Structures ◽  
Nitric Oxide Production ◽  
Regional Cerebral Blood ◽  
Oxide Production ◽  
Arterial Blood ◽  
The Brain

The endogenous vasodilator and signaling molecule nitric oxide has been implicated in cerebral hyperemia, sympathoexcitation, and seizures induced by hyperbaric oxygen (HBO2) at or above 3 atmospheres absolute (ATA). It is unknown whether these events in the onset of central nervous system oxygen toxicity originate within specific brain structures and whether blood flow is diverted to the brain from peripheral organs with high basal flow, such as the kidney. To explore these questions, total and regional cerebral blood flow (CBF) were measured in brain structures of the central autonomic network in anesthetized rats in HBO2at 6 ATA. Electroencephalogram (EEG) recordings, cardiovascular hemodynamics, and renal blood flow (RBF) were also monitored. As expected, mean arterial blood pressure and total and regional CBF increased preceding EEG spikes while RBF was unaltered. Of the brain structures examined, the earliest rise in CBF occurred in the striatum, suggesting increased neuronal activation. Continuous unilateral or bilateral striatal infusion of the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester attenuated CBF responses in that structure, but global EEG discharges persisted and did not differ from controls. Our novel findings indicate that: 1) cerebral hyperemia in extreme HBO2in rats does not occur at the expense of renal perfusion, highlighting the remarkable autoregulatory capability of the kidney, and 2) in spite of a sentinel increase in striatal blood flow, additional brain structure(s) likely govern the pathogenesis of HBO2-induced seizures because EEG discharge latency was unchanged by local blockade of striatal nitric oxide production and concomitant hyperemia.

Sign in / Sign up

Export Citation Format

Share Document