scholarly journals Alteration of Neuroinflammation Detected by 18F-GE180 PET Imaging in Place-Conditioned Rats with Morphine Withdrawal

2021 ◽  
Author(s):  
Junpeng Li ◽  
Da Shao ◽  
Donglang Jiang ◽  
Qi Huang ◽  
Yihui Guan ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Pet Imaging ◽  
Drug Withdrawal ◽  
Treatment Phase ◽  
Response Assessment ◽  
Brain Regions ◽  
Conditioned Aversion ◽  
Morphine Withdrawal ◽  
Sprague Dawley ◽  
Male Adult

Abstract Background: Accumulating evidence indicates that neuroinflammation significantly contributes to drug addiction, but the conversion of neuroinflammation after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of neuroinflammation during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180.Methods: Twelve male adult Sprague-Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t-test using SPM8. Results: Both the DW group and the CPA group spent less time in the conditioning cage during the posttest phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. -159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. Conclusion: In morphine-dependent rats, neuroinflammation became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this neuroinflammation induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

scholarly journals Alteration of neuroinflammation detected by 18F-GE180 PET imaging in place-conditioned rats with morphine withdrawal

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junpeng Li ◽  
Da Shao ◽  
Donglang Jiang ◽  
Qi Huang ◽  
Yihui Guan ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Pet Imaging ◽  
Drug Withdrawal ◽  
Treatment Phase ◽  
Response Assessment ◽  
Brain Regions ◽  
Conditioned Aversion ◽  
Morphine Withdrawal ◽  
Sprague Dawley ◽  
Male Adult

Abstract Background Accumulating evidence indicates that neuroinflammation (NI) significantly contributes to drug addiction, but the conversion of NI after drug withdrawal is not clear. Here, we conducted 18F-flutriciclamide (GE180) positron emission tomography (PET) imaging to investigate the conversion of NI during drug withdrawal and conditioning-induced aversion by measuring the change in microglial activation with 18F-GE180. Methods Twelve male adult Sprague–Dawley rats were subjected to morphine withdrawal by the administration of naloxone, and six of them were used to model conditioned place aversion (CPA). 18F-GE180 PET imaging was performed for 11 rats on the last day of the morphine treatment phase and for 10 rats on the response assessment phase of the behavior conditioning procedure. A 18F-GE180 template was established for spatial normalization of each individual image, and the differential 18F-GE180 uptakes between the drug withdrawal (DW) group and the drug addiction (DA) group, the CPA group and the DA group, and the CPA group and the DW group were compared by a voxel-wise two-sample t test using SPM8. Results Both the DW group and the CPA group spent less time in the conditioning cage during the post-test phase compared with the pretest phase, but only the difference in the CPA group was significant (63.2 ± 34.6 vs. − 159.53 ± 22.02, P < 0.005). Compared with the DA group, the uptake of 18F-GE180 increased mainly in the hippocampus, visual cortex, thalamus and midbrain regions and decreased mainly in the sensory-related cortices after the administration of naloxone in both the DW and CPA groups. Increased 18F-GE180 uptake was only observed in the mesolimbic regions after conditioned aversion compared with the DW group. Conclusion In morphine-dependent rats, Neuroinflammation (NI) became more severe in the addiction-involved brain regions but remitted in the sensory-related brain regions after the administration of naloxone, and this NI induced by withdrawal was further aggravated after conditioned aversion formation thus may help to consolidate the withdrawal memory.

Opioidergic system and N-methyl D-aspartate receptor (NMDA-R) hypofunction: Translational implications for the pathophysiology of psychosis and drug addiction

2011 ◽  
Vol 26 (S2) ◽  
pp. 1231-1231
Author(s):  
E.F. Buonaguro ◽  
F. Marmo ◽  
L. Avvisati ◽  
G. Latte ◽  
R. Rossi ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Drugs Of Abuse ◽  
Premotor Cortex ◽  
Region Of Interest ◽  
Brain Regions ◽  
Anterior Cingulate ◽  
Preclinical Model ◽  
Sprague Dawley ◽  
Somatosensory Cortices ◽  
Sprague Dawley Rats

Enkephalin is an opioidergic neuromodulator that has been implicated in long-term behavioural sensitization after administration of drugs of abuse. Enkephalin is also a molecular marker of GABAergic neurons in the striato-pallidal pathway that is involved in sensory-motor gating and has been considered dysfunctional in the pathophysiology of psychosis.In this study we investigated in male Sprague Dawley rats putative changes in Enkephalin transcripts by in situ hybridization after acute or subchronic administration of ketamine in either high or low subanaesthetic doses (50 mg/kg and 12 mg/kg respectively). Ketamine is a non-competitive NMDA-R antagonist that perturbs glutamate neurotransmission and provides a preclinical model of psychosis-like behaviour in rats.In the acute paradigm the expression of Enkephalin was reduced in the motor, premotor, somatosensory cortices as well as in anterior cingulate. In the subchronic paradigm Enkephalin expression was reduced in the premotor cortex, in the ventromedial caudate-putamen and in the shell of nucleus accumbens. Comparative analysis showed that the relative decrement in gene expression was not significantly different between the acute and subchronic paradigm for each region of interest.Changes in distribution of Enkephalin expression and correlation analysis of functionally related brain regions suggest that Enkephalin transcripts reduction may be implicated in the motivational aspects of drug addiction and may help explaining some aspects of the pathophysiology in ketamine-induced psychosis.

scholarly journals Amitriptyline Accelerates SERT Binding Recovery Rate in MDMA-Induced Rat Model: In Vivo 4-[18F]-ADAM PET Imaging

2021 ◽  
Author(s):  
Skye Hsin-Hsien Yeh ◽  
Chuang-Hsin Chiu ◽  
Yu-Yeh Kuo ◽  
Chi-Jung Tsai ◽  
Tsung-Hsun Yu ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Rat Model ◽  
Recovery Rate ◽  
Neuroprotective Effect ◽  
Brain Regions ◽  
Sprague Dawley ◽  
Fiber Density ◽  
Neuroprotective Effects ◽  
Immunochemical Staining

Abstract Background Numerous studies have confirmed that 3, 4-Methylenedioxymethamphetamine (MDMA) produces long-lasting changes to the serotonergic system and decreases the density of the serotonin reuptake transporter (SERT). However, amitriptyline (AMI) is a potent neuroprotector that can cause devastating neuropathologic injury. Use of 4-[18F]-ADAM, a SERT-specific radionuclide as a molecular imaging agent, facilitates longitudinal, non-invasive assessment of SERT activity/expression post-MDMA. We used 4-[18F]-ADAM PET imaging to access the longitudinal alteration of SERT binding and evaluate the synergistic neuroprotective effect of MDMA and SERT inhibition by AMI in rat model.Materials and Methods The adult male Sprague–Dawley (SD) rats are grouped into four according to drug administration (Group 1: saline, Group 2: MDMA 10mg/kg i.p., Group 3: MDMA 10mg/kg i.p. with AMI 5 mg/kg i.p., Group 4: AMI 5 mg/kg i.p.). All drugs were administrated twice daily for 4 successive days (Day 1 to Day 4). Post-drug 4-[18F]-ADAM PET scans were performed on day 14, day 21 and day 28 to measure the SERT occupancy/recovery. After the last PET imaging, SERT-positive cells were measured quantitatively using immunochemical staining.Results In response to MDMA treatment regimens, SERT binding was significantly reduced in rat brain. Recovery rate (normalized to baseline) in the MDMA group, at day 14 was 64.34% ± 2.05%, progressively increased to 70.70% ± 3.96% at day 28. Recovery rate in the MDMA group varies based on region-specific. AMI dramatically increased SERT binding in all brain regions, enhancing average ~24% recovery rate at day 14 when compared with the MDMA group (MDMA 64.34% ± 2.05% vs. MDMA+ AMI 87.76% ± 2.98%), reaching 84.38% ± 2.05% at day 28. The immunochemical staining revealed that MDMA treatment reduced SERT immunoactivity densities in all brain regions, whereas AMI markedly increased the serotonergic fiber density after MDMA-induction that confirmed the PET findings.Conclusions Using in vivo longitudinal PET imaging, we demonstrated that SERT recovery was positively correlated with the duration of MDMA abstinence, implying the lower SERT densities in MDMA-induced rats reflected neurotoxic effects, varied region-specific, and reversible. AMI globally accelerated the recovery rate of SERT binding and increased SERT fiber density with possible neuroprotective effects.

scholarly journals miR-142 downregulation alleviates rat PTSD-like behaviors, reduces the level of inflammatory cytokine expression and apoptosis in hippocampus, and upregulates the expression of fragile X mental retardation protein

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Peng-Yin Nie ◽  
Lei Tong ◽  
Ming-Da Li ◽  
Chang-Hai Fu ◽  
Jun-Bo Peng ◽  
...  
Keyword(s):  
Fragile X ◽  
Brain Regions ◽  
Synaptic Proteins ◽  
Sprague Dawley ◽  
Post Traumatic Stress ◽  
Proinflammatory Mediators ◽  
Upstream Regulator ◽  
Trace Fear ◽  
Factor Α

Abstract Background FMRP is a selective mRNA-binding protein that regulates protein synthesis at synapses, and its loss may lead to the impairment of trace fear memory. Previously, we found that FMRP levels in the hippocampus of rats with post-traumatic stress disorder (PTSD) were decreased. However, the mechanism underlying these changes remains unclear. Methods Forty-eight male Sprague-Dawley rats were randomly divided into four groups. The experimental groups were treated with the single-prolonged stress (SPS) procedure and injected with a lentivirus-mediated inhibitor of miR-142-5p. Behavior test as well as morphology and molecular biology experiments were performed to detect the effect of miR-142 downregulation on PTSD, which was further verified by in vitro experiments. Results We found that silence of miRNA-142 (miR-142), an upstream regulator of FMRP, could alleviate PTSD-like behaviors of rats exposed to the SPS paradigm. MiR-142 silence not only decreased the levels of proinflammatory mediators, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, but also increased the expressive levels of synaptic proteins including PSD95 and synapsin I in the hippocampus, which was one of the key brain regions associated with PTSD. We further detected that miR-142 silence also downregulated the transportation of nuclear factor kappa-B (NF-κB) into the nuclei of neurons and might further affect the morphology of neurons. Conclusions The results revealed miR-142 downregulation could alleviate PTSD-like behaviors through attenuating neuroinflammation in the hippocampus of SPS rats by binding to FMRP.

Enzymatic condensation of dopamine and acetaldehyde: a salsolinol synthase from rat brain

Biologia ◽  
2011 ◽  
Vol 66 (6) ◽  
Author(s):  
Xuechai Chen ◽  
Abida Arshad ◽  
Hong Qing ◽  
Rui Wang ◽  
Jianqing Lu ◽  
...  
Keyword(s):  
Enzyme Activity ◽  
Substantia Nigra ◽  
Human Subjects ◽  
Enzymatic Reaction ◽  
Brain Regions ◽  
Activity Detection ◽  
Reaction Products ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Salsolinol Synthase

AbstractSalsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; Sal) is structurally similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which is supposed to have a role in the development of Parkinson-like syndrome in both human and non-human subjects. In the human brain, the amount of (R)-enantiomer of Sal is much higher than (S)-enantiomer, suggesting that a putative enzyme may participate in the synthesis of (R)-salsolinol, called (R)-salsolinol synthase. In this study, the (R)-salsolinol synthase activity in the condensation of dopamine and acetaldehyde was investigated in the crude extracts from the brains of Sprague Dawley rats. Identification of the enzymatic reaction products and enzyme activity detection were achieved by HPLC-electrochemical detection. The discovery of this enzyme activity in rat’s brain indicates the natural existence of (R)-salsolinol synthase in the brains of humans and rats, and it is distributed in most brain regions of rat with higher activity in soluble proteins extracted from striatum and substantia nigra.

scholarly journals Maternal Melatonin Therapy Attenuates Methyl-Donor Diet-Induced Programmed Hypertension in Male Adult Rat Offspring

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1407 ◽  
Author(s):  
You-Lin Tain ◽  
Julie Chan ◽  
Chien-Te Lee ◽  
Chien-Ning Hsu
Keyword(s):  
Methylation Status ◽  
Normal Diet ◽  
Male Offspring ◽  
Adult Offspring ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Deficient Diet ◽  
Male Adult ◽  
Methyl Donor ◽  
Adult Rat

Although pregnant women are advised to consume methyl-donor food, some reports suggest an adverse outcome. We investigated whether maternal melatonin therapy can prevent hypertension induced by a high methyl-donor diet. Female Sprague-Dawley rats received either a normal diet, a methyl-deficient diet (L-MD), or a high methyl-donor diet (H-MD) during gestation and lactation. Male offspring were assigned to four groups (n = 7–8/group): control, L-MD, H-MD, and H-MD rats were given melatonin (100 mg/L) with their drinking water throughout the period of pregnancy and lactation (H-MD+M). At 12 weeks of age, male offspring exposed to a L-MD or a H-MD diet developed programmed hypertension. Maternal melatonin therapy attenuated high methyl-donor diet-induced programmed hypertension. A maternal L-MD diet and H-MD diet caused respectively 938 and 806 renal transcripts to be modified in adult offspring. The protective effects of melatonin against programmed hypertension relate to reduced oxidative stress, increased urinary NO2− level, and reduced renal expression of sodium transporters. A H-MD or L-MD diet may upset the balance of methylation status, leading to alterations of renal transcriptome and programmed hypertension. A better understanding of reprogramming effects of melatonin might aid in developing a therapeutic strategy for the prevention of hypertension in adult offspring exposed to an excessive maternal methyl-supplemented diet.

Refining the Effects Observed in a Developmental Neurobehavioral Study of Ammonium Perchlorate Administered Orally in Drinking Water to Rats. II. Behavioral and Neurodevelopment Effects

2005 ◽  
Vol 24 (6) ◽  
pp. 451-467 ◽  
Author(s):  
Raymond G. York ◽  
John Barnett ◽  
Michael F. Girard ◽  
David R. Mattie ◽  
Marni V. K. Bekkedal ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ammonium Perchlorate ◽  
Brain Regions ◽  
Male Rats ◽  
Male Rat ◽  
Sprague Dawley ◽  
Continuous Access ◽  
Brain Morphometry ◽  
The Central Nervous System ◽  
The Right

A developmental neurotoxicity study was conducted to generate additional data on the potential functional and morphological hazard to the central nervous system caused by ammonium perchlorate in offspring from in utero and lactation exposure. Female Sprague-Dawley rats (23 to 25/group) were given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 10.0 mg/kg-day perchlorate in the drinking water beginning 2 weeks prior to mating and continuing through day 10 of lactation for the behavioral function assessment or given continuous access to 0 (carrier), 0.1, 1.0, 3.0, and 30.0 mg/kg-day beginning on gestation day 0 and continuing through day 10 of lactation for neurodevelopment assessments. Motor activity was conducted on postpartum days 14, 18, and 22 and juvenile brain weights, neurohistopathological examinations, and regional brain morphometry were conducted on postpartum days 10 and 22. This research revealed a sexually dimorphic response, with some brain regions being larger in perchlorate-treated male rats than in comparable controls. Even so, there was no evidence of any obvious exposure-related effects on male rat brain weights or neuropathology. The most consistent exposure-related effect in the male pups was on the thickness of the corpus callosum, with both the right- and left-sided measures of the thickness of this white matter tract being significantly greater for the male pups in the 0.1 and 1.0 mg/kg-day exposure groups. The behavioral testing suggests prenatal exposure to ammonium perchlorate does not affect the development of gross motor movements in the pups.

KELULUT HONEY SUPPLEMENTATION PREVENTS SPERM AND TESTICULAR OXIDATIVE DAMAGE IN STREPTOZOTOCIN-INDUCED DIABETIC RATS

2017 ◽  
Vol 79 (3) ◽  
Author(s):  
Siti Balkis Budin ◽  
Fatin Farhana Jubaidi ◽  
Siti Nur Farahana Mohd Noor Azam ◽  
Nur Liyana Mohamed Yusof ◽  
Izatus Shima Taib ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Sperm Quality ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Control Groups ◽  
Sod Activity ◽  
Male Adult ◽  
Pathological Conditions ◽  
Sprague Dawley Rats

Previous studies found that Kelulut Honey produced by Trigona spp. bees is able to prevent oxidative damage in various pathological conditions.  Thus, the present study aimed to determine whether Kelulut Honey could prevent the sperm and testicular damage in streptozotocin-induced diabetic rats. Male Adult male Sprague-Dawley rats were divided into four groups: Non-Diabetic (NDM), Non-Diabetic with Kelulut Honey supplementation (NDMKH), Diabetic without supplementation (DM) and Diabetic with Kelulut Honey supplementation (DMKH).  Kelulut honey was given at the dose of 2.0 g/kg weight daily via gavage for 28 consecutive days. Results showed that sperm quality produced by diabetic rats supplemented with Kelulut honey significantly improved compared to the diabetic control groups (p<0.05). SOD activity and GSH level increased significantly (p<0.05) whereas PC and MDA levels significantly decreased in sperm and testis of DMKH rats when compared to DM rats (p<0.05). Histological observation showed obvious increase in spermatozoa in the lumen of epididymis and increased spermatogenic cells density in the testis of DMKH group.  In conclusion, Kelulut Honey has a potential in preventing the damage of sperm and testis in diabetic rats.

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