scholarly journals Role of Brain Derived Extracellular Vesicles in Decoding Sex Differences Associated with Nicotine Self-Administration

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1883
Author(s):  
Sneh Koul ◽  
Victoria L. Schaal ◽  
Subhash Chand ◽  
Steven T. Pittenger ◽  
Neetha Nanoth Vellichirammal ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Brain Function ◽  
Cell Communication ◽  
Clinical Importance ◽  
The United States ◽  
Female Rats ◽  
Molecular Pathways ◽  
Self Administration ◽  
Critical Knowledge ◽  
Male And Female Rats

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.

scholarly journals Female rats self-administer heroin by vapor inhalation

2020 ◽  
Author(s):  
Arnold Gutierrez ◽  
Jacques D. Nguyen ◽  
Kevin M. Creehan ◽  
Michael A. Taffe
Keyword(s):  
The United States ◽  
Route Of Administration ◽  
Female Rats ◽  
Initial Increase ◽  
Prescription Opioids ◽  
Self Administration ◽  
Heroin Use ◽  
Male And Female Rats ◽  
Opioid Drugs ◽  
Withdrawal Signs

AbstractOver the last two decades the United States has experienced a significant increase in the medical and non-medical use of opioid drugs, resulting in record numbers of opioid-related overdoses and deaths. There was an initial increase in non-medical use of prescription opioids around 2002, followed later by increased heroin use and then most recently fentanyl. Inhalation is a common route of administration for opioids, with a documented history spanning back to Mediterranean antiquity and up through modern use with e-cigarette devices. Unfortunately, preclinical studies using inhalation as the route of administration remain relatively few. This study was conducted to determine the efficacy of e-cigarette vapor inhalation of heroin in rats. Non-contingent exposure to heroin or methadone vapor produced anti-nociceptive efficacy in male and female rats. Female rats were trained to self-administer heroin vapor; the most-preferring half of the distribution obtained more vapor reinforcers when the concentration of heroin was reduced in the vapor vehicle and when pre-treated with the opioid receptor antagonist naloxone. The anti-nociceptive effect of heroin self-administered by vapor was identical in magnitude to that produced by intravenous self-administration. Finally, anxiety-like behavior increased 24-48 hours after last heroin vapor access, consistent with withdrawal signs observed after intravenous self-administration. In sum, these studies show that rewarding and anti-nociceptive effects of heroin are produced in rats by vapor inhalation using e-cigarette technology. Importantly, self-administration models by this route can be deployed to determine health effects of inhaled heroin or other opioids.

scholarly journals Sex Differences in Escalated Methamphetamine Self-Administration and Altered Gene Expression Associated With Incubation of Methamphetamine Seeking

2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  
Keyword(s):  
Sex Differences ◽  
Nucleus Accumbens ◽  
Fixed Ratio ◽  
Female Rats ◽  
Male Rats ◽  
Mrna Levels ◽  
Self Administration ◽  
Male And Female ◽  
Orexin Receptors ◽  
Male And Female Rats

Abstract Background Methamphetamine (METH) use disorder is prevalent worldwide. There are reports of sex differences in quantities of drug used and relapses to drug use among individuals with METH use disorder. However, the molecular neurobiology of these potential sex differences remains unknown. Methods We trained rats to self-administer METH (0. 1 mg/kg/infusion, i.v.) on an fixed-ratio-1 schedule for 20 days using two 3-hour daily METH sessions separated by 30-minute breaks. At the end of self-administration training, rats underwent tests of cue-induced METH seeking on withdrawal days 3 and 30. Twenty-four hours later, nucleus accumbens was dissected and then used to measure neuropeptide mRNA levels. Results Behavioral results show that male rats increased the number of METH infusions earlier during self-administration training and took more METH than females. Both male and female rats could be further divided into 2 phenotypes labeled high and low takers based on the degree of escalation that they exhibited during the course of the METH self-administration experiment. Both males and females exhibited incubation of METH seeking after 30 days of forced withdrawal. Females had higher basal mRNA levels of dynorphin and hypocretin/orexin receptors than males, whereas males expressed higher vasopressin mRNA levels than females under saline and METH conditions. Unexpectedly, only males showed increased expression of nucleus accumbens dynorphin after METH self-administration. Moreover, there were significant correlations between nucleus accumbens Hcrtr1, Hcrtr2, Crhr2, and Avpr1b mRNA levels and cue-induced METH seeking only in female rats. Conclusion Our results identify some behavioral and molecular differences between male and female rats that had self-administered METH. Sexual dimorphism in responses to METH exposure should be considered when developing potential therapeutic agents against METH use disorder.

Effect of cocaine self-administration on striatal PKA-regulated signaling in male and female rats

2006 ◽  
Vol 191 (2) ◽  
pp. 263-271 ◽  
Author(s):  
Wendy J. Lynch ◽  
Drew D. Kiraly ◽  
Barbara J. Caldarone ◽  
Marina R. Picciotto ◽  
Jane R. Taylor
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Effects of nicotine exposure on oral methamphetamine self-administration, extinction, and drug-primed reinstatement in adolescent male and female rats

2020 ◽  
Vol 209 ◽  
pp. 107927 ◽  
Author(s):  
Zachary R. Harmony ◽  
Erin M. Alderson ◽  
Israel Garcia-Carachure ◽  
Laurence D. Bituin ◽  
Cynthia A. Crawford
Keyword(s):  
Female Rats ◽  
Adolescent Male ◽  
Nicotine Exposure ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats

2012 ◽  
Vol 121 (3) ◽  
pp. 240-246 ◽  
Author(s):  
Matthew W. Feltenstein ◽  
Shannon M. Ghee ◽  
Ronald E. See
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

scholarly journals Assessing the effects of chronic sazetidine-A delivery on nicotine self-administration in both male and female rats

2012 ◽  
Vol 222 (2) ◽  
pp. 269-276 ◽  
Author(s):  
Joshua E. Johnson ◽  
Susan Slade ◽  
Corinne Wells ◽  
Ann Petro ◽  
Hannah Sexton ◽  
...  
Keyword(s):  
Female Rats ◽  
Self Administration ◽  
Male And Female ◽  
Male And Female Rats

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
Keyword(s):  
Rat Brain ◽  
Early Adolescence ◽  
Drugs Of Abuse ◽  
Specific Binding ◽  
Biological Effects ◽  
The United States ◽  
Female Rats ◽  
Opioid Use ◽  
Male And Female Rats ◽  
The Brain

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.

scholarly journals Effects of Kappa Opioid Receptor Agonists on Fentanyl vs. Food Choice in Male and Female Rats: Contingent vs. Non-Contingent Administration

2020 ◽  
Author(s):  
E. Andrew Townsend
Keyword(s):  
Opioid Receptor ◽  
Food Choice ◽  
Food Reinforcement ◽  
Abuse Liability ◽  
Kappa Opioid Receptor ◽  
Female Rats ◽  
Self Administration ◽  
Kappa Opioid ◽  
Male And Female ◽  
Male And Female Rats

AbstractRationaleStrategies are needed to decrease the abuse liability of mu opioid receptor (MOR) agonists. One strategy under consideration is to combine MOR agonists with kappa opioid receptor (KOR) agonists.ObjectivesThe effects of KOR-agonists (U50488, nalfurafine) on fentanyl-versus-food choice were compared under conditions where the KOR agonists were added to the self-administered fentanyl (contingent delivery) or administered as pretreatments (non-contingent delivery) in male and female rats. The effects of increasing and decreasing the magnitude of the alternative food reinforcer were also determined.MethodsRats were trained to respond under a concurrent schedule of fentanyl (0, 0.32-10 μg/kg/infusion) and food reinforcement. In Experiment 1, U50488 and nalfurafine were co-administered with fentanyl as fixed-proportion mixtures (contingent administration). In Experiment 2, U50488 (1-10 mg/kg) and nalfurafine (3.2-32 μg/kg) were administered as acute pretreatments (non-contingent administration). nor-BNI (32 mg/kg) was administered prior to contingent and non-contingent KOR-agonist treatment in Experiment 3. Experiment 4 evaluated the effects of increasing and decreasing the magnitude of the non-drug reinforcer.ResultsBoth U50488 and nalfurafine decreased fentanyl choice when administered contingently, demonstrating that KOR agonists punish opioid choice. Non-contingent U50488 and nalfurafine administration decreased rates of fentanyl and food self-administration without altering fentanyl choice. Both contingent and non-contingent U50488 and nalfurafine effects on fentanyl choice were attenuated by nor-BNI. Fentanyl choice was sensitive to increases and decreases in the magnitude of the non-drug reinforcer.ConclusionsThese results demonstrate that the effects of KOR agonists on fentanyl reinforcement are dependent upon the contingencies under which they are administered.

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