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.

Hippocampal glutamine synthetase: insensitivity to glucocorticoids and stress

1990 ◽  
Vol 258 (5) ◽  
pp. E894-E897 ◽  
Author(s):  
G. C. Tombaugh ◽  
R. M. Sapolsky
Keyword(s):  
Skeletal Muscle ◽  
Central Nervous System ◽  
Nervous System ◽  
Glutamine Synthetase ◽  
Glutamate Metabolism ◽  
Glutamatergic Synapses ◽  
Adult Rats ◽  
Glucocorticoid Induction ◽  
The Central Nervous System ◽  
The Brain

Glucocorticoids enhance the neurotoxic potential of several insults to the rat hippocampus that involve overactivation of glutamatergic synapses. These hormones also stimulate the synthesis of glutamine synthetase (GS) in peripheral tissue. Because this enzyme helps regulate glutamate metabolism in the central nervous system, glucocorticoid induction of GS in the brain may underlie the observed synergy. We have measured GS activity in the hippocampus and skeletal muscle (plantaris) of adult rats after bilateral adrenalectomy (ADX), corticosterone (Cort) replacement, or stress. No significant changes in GS were observed in hippocampal tissue, whereas muscle GS was significantly elevated after Cort treatment or stress and was reduced after ADX. These results suggest that Cort-induced shifts in GS activity probably do not explain Cort neurotoxicity, although the stress-induced rise in muscle GS may be relevant to certain types of myopathy.

scholarly journals The Effects of Exposure to Mephedrone During Adolescence on Brain Neurotransmission and Neurotoxicity in Adult Rats

2018 ◽  
Vol 34 (3) ◽  
pp. 525-537 ◽  
Author(s):  
Katarzyna Kamińska ◽  
Karolina Noworyta-Sokołowska ◽  
Anna Górska ◽  
Joanna Rzemieniec ◽  
Agnieszka Wnuk ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Glutamate Release ◽  
Cortical Cell ◽  
Synaptic Cleft ◽  
In Vivo Microdialysis ◽  
Male Rats ◽  
Adolescent Male ◽  
Turnover Rates ◽  
Adult Rats

Abstract According to the European Drug Report (2016), the use of synthetic cathinones, such as mephedrone, among young people has rapidly increased in the last years. Studies in humans indicate that psychostimulant drug use in adolescence increases risk of drug abuse in adulthood. Mephedrone by its interaction with transporters for dopamine (DAT) and serotonin (SERT) stimulates their release to the synaptic cleft. In animal studies, high repeated doses of mephedrone given to adolescent but not adult mice or rats induced toxic changes in 5-hydroxytryptamine (5-HT) neurons. The aim of our study was to investigate the effects of mephedrone given in adolescence on brain neurotransmission and possible neuronal injury in adult rats. Adolescent male rats were given mephedrone (5 mg/kg) for 8 days. In vivo microdialysis in adult rats showed an increase in dopamine (DA), 5-HT, and glutamate release in the nucleus accumbens and frontal cortex but not in the striatum in response to challenge dose in animals pretreated with mephedrone in adolescence. The 5-HT and 5-hydroxyindoleacetic acid contents decreased in the striatum and nucleus accumbens while DA turnover rates were decreased in the striatum and nucleus accumbens. The oxidative damage of DNA assessed with the alkaline comet assay was found in the cortex of adult rats. Therefore, the administration of repeated low doses of mephedrone during adolescence does not seem to induce injury to 5-HT and DA neurons. The oxidative stress seems to be responsible for possible damage of cortical cell bodies which causes maladaptive changes in serotonergic and dopaminergic neurons.

scholarly journals Differential effects of D-cycloserine and amantadine on motor behavior and D2/3 receptor binding in the nigrostriatal and mesolimbic system of the adult rat

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Susanne Nikolaus ◽  
Hans-Jörg Wittsack ◽  
Frithjof Wickrath ◽  
Anja Müller-Lutz ◽  
Hubertus Hautzel ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Motor Behavior ◽  
Small Animal ◽  
Exploratory Activity ◽  
Reference Region ◽  
Post Challenge ◽  
Adult Rats ◽  
Adult Rat ◽  
Agonist And Antagonist ◽  
The Brain

Abstract D-cycloserine (DCS) and amantadine (AMA) act as partial NMDA receptor (R) agonist and antagonist, respectively. In the present study, we compared the effects of DCS and AMA on dopamine D2/3R binding in the brain of adult rats in relation to motor behavior. D2/3R binding was determined with small animal SPECT in baseline and after challenge with DCS (20 mg/kg) or AMA (40 mg/kg) with [123I]IBZM as radioligand. Immediately post-challenge, motor/exploratory behavior was assessed for 30 min in an open field. The regional binding potentials (ratios of the specifically bound compartments to the cerebellar reference region) were computed in baseline and post-challenge. DCS increased D2/3R binding in nucleus accumbens, substantia nigra/ventral tegmental area, thalamus, frontal, motor and parietal cortex as well as anterodorsal and posterior hippocampus, whereas AMA decreased D2/3R binding in nucleus accumbens, caudateputamen and thalamus. After DCS, ambulation and head-shoulder motility were decreased, while sitting was increased compared to vehicle and AMA. Moreover, DCS increased rearing relative to AMA. The regional elevations of D2/3R binding after DCS reflect a reduction of available dopamine throughout the mesolimbocortical system. In contrast, the reductions of D2/3R binding after AMA indicate increased dopamine in nucleus accumbens, caudateputamen and thalamus. Findings imply that, after DCS, nigrostriatal and mesolimbic dopamine levels are directly related to motor/exploratory activity, whereas an inverse relationship may be inferred for AMA.

scholarly journals A Possible Mechanism for the Action of Adrenomedullin in Brain to Stimulate Stress Hormone Secretion

Endocrinology ◽  
2004 ◽  
Vol 145 (11) ◽  
pp. 4890-4896 ◽  
Author(s):  
Meghan M. Taylor ◽  
Willis K. Samson
Keyword(s):  
Hpa Axis ◽  
Hormone Secretion ◽  
Plasma Corticosterone ◽  
Male Rats ◽  
Stress Hormone ◽  
Elevated Plasma ◽  
The Central Nervous System ◽  
Neuroendocrine Responses ◽  
The Brain

Abstract Adrenomedullin (AM) has been reported to have actions at each level of the hypothalamo-pituitary-adrenal (HPA) axis, suggesting that the peptide plays a role in the organization of the neuroendocrine responses to stress. We examined the mechanism by which AM regulates the central nervous system branch of the HPA axis as well as the possible role of AM in the modulation of the releases of two other hormones, prolactin and GH, whose secretions also are altered by stress. Intracerebroventricular administration of AM led to elevated plasma corticosterone levels in unrestrained, conscious male rats. This effect was abrogated by pretreatment with a CRH antagonist, suggesting that AM activates the HPA axis by causing the release of CRH into hypophyseal portal vessels. In addition, AM given intracerebroventricularly stimulated the release of prolactin but did not alter the secretion of GH. We propose that AM produced in the brain may be an important neuromodulator of the hormonal stress response.

scholarly journals The Effect of Gender on Brain Tissue Changes Induced by Renal Ischemia-Reperfusion Injury in Adult Rats

2019 ◽  
Vol 8 (2) ◽  
pp. 113-118
Author(s):  
Fakhri Armin ◽  
Fariba Azarkish ◽  
Ali Atash Ab Parvar ◽  
Aghdas Dehghani
Keyword(s):  
Brain Tissue ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Sensitive Organ ◽  
The Brain

Background: Renal ischemia-reperfusion (RIR) is a common clinical injury that affects the function of other remote organs such as the brain by initiating a cascade of complex and wide-ranging inflammatory responses. RIR also follows a different course in men and women. Since there is little information on the effect of RIR on the brain as a sensitive organ in both males and females, the present research was performed to investigate the effect of gender on RIR-induced brain tissue alterations in adult rats. Materials and Methods: In this study, 28 Wistar rats (14 female and 14 male rats) weighing 200 ± 20 g were divided into the following groups: 1- male sham (MS), 2- female sham (FS), 3- male ischemia (MI) with 3-hour reperfusion (ISC3hr), and 4- Female ischemia (FI) with 3-hour reperfusion (ISC3hr). Bilateral renal ischemia was induced for 45 minutes and blood samples were taken after reperfusion for the measurements of serum blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitrite levels. The left kidney was removed for evaluation of MDA and tissue nitrite levels. Right kidney and brain tissue underwent histological examination. Results: Serum BUN level increased in both genders. Serum nitrite level was significantly different between both genders, meaning that it was increased in the female rats as compared to male ones. Overall brain tissue damage was significantly increased in males compared to females. Conclusion: RIR has an effect on the function and tissue of kidney and brain in both genders. Female rats are more susceptible to the nitric oxide system than the male ones. This study showed that male brain tissue was more susceptible to RIR. Therefore, gender is one of the important factors that should be considered in clinical treatments.

scholarly journals Temporal Profile of Transporter mRNA Expression in the Brain after Traumatic Brain Injury in Developing Rats

2019 ◽  
Author(s):  
Solomon M. Adams ◽  
Fanuel T. Hagos ◽  
Jeffrey P. Cheng ◽  
Robert S. B. Clark ◽  
Patrick M. Kochanek ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Mrna Expression ◽  
Neurovascular Unit ◽  
Post Injury ◽  
Adult Rats ◽  
Order Of Magnitude ◽  
Liver And Kidney ◽  
The Central Nervous System ◽  
The Brain

ABSTRACTTraumatic brain injury (TBI) is a leading cause of death in children and young adults; however, new pharmacologic approaches have failed to improve outcomes in clinical trials. Transporter proteins are central to the maintenance of homeostasis within the neurovascular unit, and regulate drug penetration into the brain. Our objective was to measure transporter temporal changes in expression in the hippocampus and cortex after experimental TBI in developing rats. We also evaluated the expression of transporters in brain, liver, and kidney across the age spectrum in both pediatric and adult rats. Eighty post-natal day (PND)-17 rats and four adult rats were randomized to receive controlled cortical impact (CCI), sham surgery, or no surgery. mRNA transcript counts for 27 ATP-binding cassette and solute carrier transporters were measured in the hippocampus, cortex, choroid plexus, liver, and kidney at 3h, 12h, 24h, 72h, 7d, and 14d post injury. After TBI, the expression of many transporters (Abcc2, Slc15a2, Slco1a2) decreased significantly in the first 24 hours, with a return to baseline over 7-14 days. Some transporters (Abcc4, Abab1a/b, Slc22a4) showed a delayed increase in expression. Baseline expression of transporters was of a similar order of magnitude in brain tissues relative to liver and kidney. Findings suggest that transporter-regulated processes may be impaired in the brain early after TBI and are potentially involved in the recovery of the neurovascular unit. Our data also suggest that transport-dependent processes in the brain are of similar importance as those seen in organs involved in drug metabolism and excretion.Significance StatementBaseline transporter mRNA expression in the central nervous system is of similar magnitude as liver and kidney, and experimental traumatic brain injury is associated with acute decrease in expression of several transporters, while others show delayed increase or decrease in expression. Pharmacotherapy following traumatic brain injury should consider potential pharmacokinetic changes associated with transporter expression.

The Brain Matrix and Multifocal Brain Damage following a Single Injection of Ketamine in Young Adult Rats: Conspicuous Changes in Old Age

2002 ◽  
Vol 95 (3) ◽  
pp. 897-900 ◽  
Author(s):  
M. A. Persinger ◽  
L. S. St-Pierre
Keyword(s):  
Adipose Tissue ◽  
Single Injection ◽  
Neuronal Loss ◽  
The Other ◽  
Male Rats ◽  
Adult Rats ◽  
Spontaneous Seizures ◽  
Seizure Model ◽  
One Year ◽  
The Brain

Male rats were seized with lithium and pilocarpine and then injected within 30 min. with either acepromazine or ketamine. These rats as well as age-matched normal rats were observed daily for one year. The rats which had received the ketamine after the seizures were significantly heavier than either the normal rats or the other group of seized rats. The bulk of this increased weight was due to the marked increase in white, extremely dense adipose tissue. Compared to the acepromazine-treated rats, the ketamine-treated rats did not exhibit spontaneous seizures and exhibited cerebral widths comparable to normal rats. These results suggest that the multifocal, graded neuronal loss associated with this seizure model may allow other “configurations” to emerge that can support normal behaviors as well as new characteristics.

scholarly journals Astrocyte-derived thrombospondin induces cortical synaptogenesis in a sex-specific manner

2021 ◽  
Author(s):  
Anna Mazur ◽  
Ean H. Bills ◽  
Brandon J. Henderson ◽  
W. Christopher Risher
Keyword(s):  
Cortical Neurons ◽  
Neuronal Response ◽  
Male Rats ◽  
Estrogen Signaling ◽  
Synaptic Connectivity ◽  
The Central Nervous System ◽  
17Β Estradiol ◽  
Males And Females ◽  
Cortical Synapses ◽  
The Brain

AbstractThe regulation of synaptic connectivity in the brain is vital to proper functioning and development of the central nervous system (CNS). Formation of neural networks in the CNS has been shown to be heavily influenced by astrocytes, which secrete factors, including thrombospondin (TSP) family proteins, that promote synaptogenesis. However, whether this process is different between males and females has not been thoroughly investigated. In this study, we found that cortical neurons purified from newborn male rats showed a significantly more robust synaptogenic response compared to female-derived cells when exposed to factors secreted from astrocytes. This difference was driven largely by the neuronal response to TSP2, which increased synapses in male neurons while showing no effect on female neurons. Blockade of endogenous 17β-estradiol production with letrozole normalized the TSP response between male and female cells, indicating a level of regulation by estrogen signaling. Our results suggest that TSP-induced synaptogenesis is critical for the development of male but not female cortical synapses, contributing to sex differences in astrocyte-mediated synaptic connectivity.

Further evidence that brain histamine H2 receptors are stimulatory in the control of prolactin in the rat

1988 ◽  
Vol 119 (4) ◽  
pp. 488-492 ◽  
Author(s):  
Carmela Netti ◽  
Valeria Sibilia ◽  
Francesca Guidobono ◽  
Isabella Villa ◽  
Paola Franco ◽  
...  
Keyword(s):  
Prolactin Secretion ◽  
Male Rats ◽  
Normal Male ◽  
Brain Histamine ◽  
H2 Receptors ◽  
The Central Nervous System ◽  
Brain Ventricle ◽  
The Brain ◽  
Chemical Analogue ◽  
Stimulation Of

Abstract. The effects of administration into the brain ventricle of H2 receptor agonists (4-methylhistamine, 0.8 μmol/rat; dimaprit, 0.4–0.8 μmol/rat), H2 antagonists (cimetidine, 0.8 μmol/rat; ranitidine, 0.4–0.8 μmol/rat; famotidine, 0.03 μmol/rat) and of the dimaprit chemical analogue SK&F 91487 (0.4 μmol/rat) on unstimulated and histamine-stimulated prolactin secretion in normal male rats were studied. The H2 agonist 4-methylhistamine caused a significant increase in unstimulated blood PRL, whereas dimaprit, SK&F 91487, and the H2 antagonists tested did not change PRL levels. 4-Methylhistamine significantly enhanced the stimulatory effects of histamine on prolactin, whereas all the H2 antagonists inhibited histamine-induced prolactin release. The inhibition of histamine-induced prolactin secretion by the H2 agonist dimaprit is nonspecific, since its chemical analogue SK&F 91487, which has no H2 agonist activity, also inhibits it. These results indicate that stimulation of the H2 receptors in the central nervous system is facilitatory for PRL secretion, suggesting that the activation of H2 receptors may contribute to the PRL-releasing effects of histamine.

scholarly journals Postweaning Iron Deficiency in Male Rats Leads to Long-Term Hyperactivity and Decreased Reelin Gene Expression in the Nucleus Accumbens

2019 ◽  
Author(s):  
Noriko Nishikura ◽  
Kodai Hino ◽  
Tomoko Kimura ◽  
Yasuhiro Uchimura ◽  
Shinjiro Hino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nucleus Accumbens ◽  
Iron Deficiency ◽  
Male Rats ◽  
Juvenile Period ◽  
Synaptic Density ◽  
Adequate Diet ◽  
Age Related ◽  
The Brain

ABSTRACT Background Epidemiological research indicates that iron deficiency (ID) in infancy correlates with long-term cognitive impairment and behavioral disturbances, despite therapy. However, the mechanisms underlying these effects are unknown. Objective We investigated how ID affected postweaning behavior and monoamine concentration in rat brains to determine whether ID during the juvenile period affected gene expression and synapse formation in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Methods Fischer 344/Jcl postweaning male rats aged 21–39 d were fed low-iron diets (0.35 mg/kg iron; ID group) or standard AIN-93 G diets [3.5 mg/kg iron; control (CN) group]. After day 39, all rats were fed the iron-adequate diet. The locomotor activity was evaluated by the open field and elevated plus maze tests at 8 and 12 wk of age. Monoamine concentrations in the brain were analyzed using HPLC at 9 and 13 wk of age. Comprehensive gene expression analysis was performed in the PFC and NAcc at 13 wk of age. Finally, we investigated synaptic density in the PFC and NAcc by synaptophysin immunostaining. Results Behavioral tests revealed a significant reduction of the age-related decline in the total distance traveled in ID rats compared with CN rats (P < 0.05), indicating that ID affected hyperactivity, which persisted into adulthood (13 wk of age). At this age, reelin (Reln) mRNA expression (adjusted P < 0.01) decreased and synaptic density (P < 0.01) increased in the NAcc in the ID group. Regarding the mesolimbic pathway, homovanillic acid concentration increased in the NAcc, whereas the dopamine concentration decreased in the ventral midbrain. Conclusions Our results suggest that ID during the postweaning period in male rats, despite complete iron repletion following ID, led to long-term hyperactivity via monoamine disturbance in the brain and an alteration in the synaptic plasticity accompanied by downregulation of Reln expression in the NAcc.

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