scholarly journals Chronic Developmental Lead Exposure increases μ-Opiate Receptor Levels in the Adolescent Rat Brain

2020 ◽  
Author(s):  
Damaris Albores-Garcia ◽  
Jennifer L McGlothan ◽  
Zoran Bursac ◽  
Tomás R. Guilarte

AbstractOpioid use and abuse has reached epidemic proportion in the United States resulting in a significant numbers of deaths due to overdose. While environmental factors are implicated in opioid addiction, less is known about the role of exposure to environmental pollutants on the brain opioid system. Human and preclinical studies have suggested an association between childhood lead (Pb2+) intoxication and proclivity to substance abuse and delinquent behavior. Opioid receptors are involved in the biological effects of opioids and other drugs of abuse. In this study, we examine the effect of chronic developmental Pb2+ exposure on μ-opioid receptor (MOR) levels in the rat brain using [3H]-D-Ala2-MePhe4-Gly-ol5 enkephalin ([3H]-DAMGO) quantitative receptor autoradiography.Our results indicate that chronic developmental Pb2+ exposure increases the levels of [3H]-DAMGO specific binding to MOR in several limbic regions of the brain in male and female rats during the pre-adolescence (PN14) and early-adolescence (PN28) period. These changes were less pronounced in late-adolescence (PN50) and adult (PN120) animals. Our findings are important because the pre-adolescence and early adolescence period is a time in which there is higher engagement in reward and drug seeking behaviors in humans.In summary, we show that chronic exposure to Pb2+ an ubiquitous and well-known environmental contaminant and neurotoxicant, alters MOR levels in brain regions associated with addiction circuits in the adolescent period with important implications to opioid drug use and abuse.

1979 ◽  
Vol 83 (2) ◽  
pp. 261-NP ◽  
Author(s):  
G. TOUBEAU ◽  
J. DESCLIN ◽  
M. PARMENTIER ◽  
J. L. PASTEELS

The distribution of immunoreactive neurones and fibres was studied in rat brain using an antiserum to rat prolactin. Neurones containing the immunoreactive material were localized in the arcuate, ventromedial, premamillary, supraoptic and paraventricular nuclei of the hypothalamus. Immunoreactive nerve fibres were widely distributed within the brain. No differences were observed in labelling between male and female rats, or as a consequence of hypophysectomy.


1976 ◽  
Vol 71 (1) ◽  
pp. 109-114 ◽  
Author(s):  
I. DONIACH ◽  
D. J. SHALE

SUMMARY From the differences in radiation profiles between 131I and 125I isotopes of iodine it would be expected that they would show different effects on thyroid function. The differences should lead to lower rates of thyroid gland destruction with 125I and hence less post-irradiation hypothyroidism. This difference in biological effect has been demonstrated in rats by indirect assessment of thyroid function. In this report the long-term effects of a range of similar doses of 131I and 125I were compared, in male and female rats, by direct assessment of thyroid function. Seventeen months after receiving 25 and 125 μCi of 131I, male and female rats showed significant elevation of serum TSH concentration and a reduction in 3 h radioiodine uptake. Rats receiving 1 and 5 μCi of 131I and all doses of 125I showed no significant changes in thyroid function. These findings confirm the previously reported differences in effect between the 131I and 125I isotopes of iodine in the rat.


2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Halimat Amin Abdulrahim ◽  
Isiaka Abdullateef Alagbonsi ◽  
Oluwasola Amuda ◽  
Noah Adavize Omeiza ◽  
Abdul-Rahuf Aderemi Feyitimi ◽  
...  

Abstract Background Lipid profile and redox status play a role in brain (dys)functions. Cannabinoid and melatonergic systems operate in the brain and contribute to brain (patho)physiology, but their roles in the modulation of brain lipid and redox status are not well-known. We studied the effect of ethanol extract of Cannabis sativa (CS) and/or melatonin (M) on the lipid profile and anti-oxidant system of the rat brain. Methods We randomly divided twenty-four (24) female Wistar rats into 4 groups (n = 6 rats each). Group 1 (control) received distilled water mixed with DMSO. Groups II–IV received CS (2 mg/kg), M (4 mg/kg), and co-administration of CS and M (CS + M) respectively via oral gavage between 8:00 am and 10:00 am once daily for 14 days. Animals underwent 12-h fasting after the last day of treatment and sacrificed under ketamine anesthesia (20 mg/kg; i.m). The brain tissues were excised and homogenized for assay of the concentrations of the total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), nitric oxide (NO), malondialdehyde (MDA), and the activities of glucose-6-phosphate dehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and acetylcholinesterase (AChE). One-way analysis of variance (ANOVA) was used to compare means across groups, followed by the least significant difference (LSD) post-hoc test. Results CS and/or M did not affect the lipid profile parameters. However, CS increased the G6PD (from 15.58 ± 1.09 to 21.02 ± 1.45 U/L; p = 0.047), GPx (from 10.47 ± 0.86 to 17.71 ± 1.04 U/L; p = 0.019), and SOD (from 0.81 ± 0.02 to 0.90 ± 0.01 μM; p = 0.007), but decreased NO (from 9.40 ± 0.51 to 6.75 ± 0.21 μM; p = 0.010) and had no effect on MDA (p = 0.905), CAT (p = 0.831), GR (p = 0.639), and AChE (p = 0.571) in comparison with the control group. M augmented the increase in G6PD (from 21.02 ± 1.45 U/L to 27.18 ± 1.81 U/L; p = 0.032) and decrease in NO (from 6.75 ± 0.21 to 4.86 ± 0.13 μM; p = 0.034) but abolished the increase in GPx (from 17.71 ± 1.04 to 8.59 ± 2.06 U/L; p = 0.006) and SOD (from 0.90 ± 0.01 to 0.70 ± 0.00 μM; p = 0.000) elicited by CS in the rat brain in comparison with the CS group. Conclusions CS and M do not alter brain lipid profile. Our data support the contention that CS elicits an anti-oxidative effect on the brain tissue and that CS + M elicits a pro-oxidant effect in rat brain.


2000 ◽  
Vol 46 (1) ◽  
pp. 30-34 ◽  
Author(s):  
A. G. Reznikov ◽  
N. D. Nosenko ◽  
L. V. Tarasenko ◽  
P. V. Sinitsyn ◽  
L. I. Polyakova

The effect of maternal stress or so-called prenatal stress (PS) on the neuroendocrine regulation of reproduction and stress reactivity of the progeny was studied. Prenatal stress prevented the formation of sex dimorphism of catecholamine content and aromatase and androgen 5a-reductase activities in the preoptic region of the brain and mediobasal hypothalamus of 10-day-old rats. Leveling of sex-specific differences in the size of the neurocyte nuclei in the suprachiasmatic nucleus was the morphological equivalent of functional disorders induced by PS. Stress and adrenergic reactivity of the hypothalamo-pituitary-adrenal system was changed in prenatally stressed males and females. Remote effects of PS are regarded as a manifestation of disorders in the hormone neurotransmitter imprinting of the neuroendocrine system.


2021 ◽  
Author(s):  
Maria Eduarda M. Botelho ◽  
Anelise S. Carlessi ◽  
Luana M. Manosso ◽  
Laura A. Borba ◽  
Airam B. de Moura ◽  
...  

Abstract Major depressive disorder is a debilitating mental disorder. Although the etiology is not fully understood, the impairment to the blood-brain barrier (BBB) integrity may be involved. Maternal deprivation was performed in the first 10 postnatal days for 3h/day. Male and female rats were divided into control and maternal deprivation. Maternal deprivation animals were subdivided and received treatment with saline, escitalopram, ketamine, or probiotic. The integrity of BBB was evaluated in the prefrontal cortex and hippocampus at postnatal days 11, 21, 41, and 61. Maternal deprivation caused BBB breakdown in the prefrontal cortex and hippocampus in female and male rats in all ages evaluated, except in the prefrontal cortex of females at postnatal day 41. In females, escitalopram, ketamine, and probiotic reversed BBB breakdown in all ages evaluated, except probiotic at postnatal day 21 (prefrontal cortex), and ketamine at postnatal days 21 and 41 (hippocampus). In males, escitalopram, ketamine, and probiotic reversed BBB breakdown in the prefrontal cortex in all ages evaluated, except escitalopram at postnatal days 41 and 61. In the hippocampus of males, BBB damage was reversed by escitalopram at postnatal day 21 and ketamine at postnatal day 41. Treatment with escitalopram, ketamine, or probiotics can prevent changes in the BBB integrity, depending on the age and sex of the animal. Clinically it is important to evaluate different treatments depending on age and sex.


2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S4-S5
Author(s):  
Nkemakonam Okoye ◽  
Gwendolyn McMillin

Abstract Background Gabapentin is a structural analogue of gamma-aminobutyric acid approved by the U.S. Food and Drug Administration (FDA) for the treatment of postherpetic neuralgia and partial-onset seizures. Gabapentin is thought to have low abuse potential and is currently not scheduled as a controlled substance by the Drug Enforcement Administration (DEA). However, recent reports indicate that gabapentin is increasingly being abused by people with opioid use disorder in an attempt to potentiate the euphoric effects from opioids and other CNS depressants. (1) In 2018, Gabapentin was the sixth most commonly prescribed medication in the United States with 67 million prescriptions dispensed. (2) The frequency of non-prescribed gabapentin misuse reported at a reference laboratory increased by 40% between 2017 and 2018. (3) It is now recognized that combination of Gabapentin with opioids and other CNS depressants increases risk of respiratory depression. (4) Of particular concern are reports showing prolonged and more severe neonatal abstinence syndrome in infants with prenatal co-exposure to gabapentin and opioids. (5) Method This retrospective study evaluated the positivity rates of 13,609 umbilical cord tissues submitted for newborn drug testing at ARUP Laboratories. The umbilical cord drug detection assay is designed to detect 49 specific drugs and drug metabolites from commonly abused drug classes including opioids, stimulants, sedative-hypnotics and hallucinogens. Reverse phase liquid chromatography coupled with triple quadrupole mass spectrometry was used for semi-quantitative measurement of the drug analytes and metabolites. Results A positive result for at least one of the measured drugs or drug metabolites was found in 3,891 (29%) out of the 13,609 analyzed umbilical cord tissues. Norbuprenorphine had the highest positivity rate (874, 6%) followed by Amphetamine (764, 6 %) and Morphine (683, 5%). Gabapentin had a positivity rate of 2% with 302 positive results. Of the 302 positive Gabapentin samples, 216 (72%) also had a positive result for at least one other drug or drug metabolite. Co-positivity with Gabapentin was highest for Norbuprenorphine (105, 35%) followed by Amphetamine (41, 14%). The median Gabapentin concentration in umbilical cord tissues that were co-positive for Norbuprenorphine and Amphetamine is 3,762 ng/g (range = 13 - 40,997 ng/g) and 1,045 ng/g (range = 15 - 40,997 ng/g) respectively. Discussion This retrospective data analysis show that there is high neonatal co-exposure rate to Gabapentin and Buprenorphine / Norbuprenorphine. Buprenorphine is a partial mu-opioid receptor agonist and co-medication with Gabapentin might be used as a strategy to enhance the feeling of euphoria from Buprenorphine in pregnant women undergoing opioid substitution therapy. References 1. Drugs 77, 403–426 (2017) 2. Medicine Use and Spending in the U.S. A Review of 2018 and Outlook to 2023 3. https://www.questdrugmonitoring.com/healthtrends (Accessed January 2020) 4. https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin (Accessed January 2020) 5. The Journal of Pediatrics 181, 286–288 (2017)


Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1883
Author(s):  
Sneh Koul ◽  
Victoria L. Schaal ◽  
Subhash Chand ◽  
Steven T. Pittenger ◽  
Neetha Nanoth Vellichirammal ◽  
...  

Smoking remains a significant health and economic concern in the United States. Furthermore, the emerging pattern of nicotine intake between sexes further adds a layer of complexity. Nicotine is a potent psychostimulant with a high addiction liability that can significantly alter brain function. However, the neurobiological mechanisms underlying nicotine’s impact on brain function and behavior remain unclear. Elucidation of these mechanisms is of high clinical importance and may lead to improved therapeutics for smoking cessation. To fill in this critical knowledge gap, our current study focused on identifying sex-specific brain-derived extracellular vesicles (BDEV) signatures in male and female rats post nicotine self-administration. Extracellular vesicles (EVs) are comprised of phospholipid nanovesicles such as apoptotic bodies, microvesicles (MVs), and exosomes based on their origin or size. EVs are garnering significant attention as molecules involved in cell–cell communication and thus regulating the pathophysiology of several diseases. Interestingly, females post nicotine self-administration, showed larger BDEV sizes, along with impaired EV biogenesis compared to males. Next, using quantitative mass spectrometry-based proteomics, we identified BDEV signatures, including distinct molecular pathways, impacted between males and females. In summary, this study has identified sex-specific changes in BDEV biogenesis, protein cargo signatures, and molecular pathways associated with long-term nicotine self-administration.


1991 ◽  
Vol 261 (5) ◽  
pp. R1276-R1285 ◽  
Author(s):  
K. E. McKenna ◽  
S. K. Chung ◽  
K. T. McVary

A preparation for the study of sexual function in anesthetized spinal male and female rats is discussed. Urethral stimulation in males elicited penile erection, ejaculation, and rhythmic contractions of the striated perineal muscles. In females, vaginal and uterine contractions and rhythmic contractions of the perineal muscles were elicited. These responses show many similarities to responses seen during sexual climax in unanesthetized humans and animals. This response, which we refer to as the urethrogenital reflex, is unaffected in either sex by gonadectomy. We determined that the urethrogenital reflex is produced by a spinal pattern generator and is under tonic descending inhibition from the brain stem. We conclude that this preparation may be a valuable model for experimental study of the neural mechanisms of sexual function in both sexes.


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