scholarly journals Adolescent Cannabinoid and Nicotine Exposure Differentially Alters Adult Nicotine Self-Administration in Males and Females

2020 ◽  
Vol 22 (8) ◽  
pp. 1364-1373 ◽  
Author(s):  
Angeline J Dukes ◽  
James P Fowler ◽  
Valeria Lallai ◽  
Anna N Pushkin ◽  
Christie D Fowler

Abstract Introduction During adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic “spice” cannabinoid agonists. Aims and Methods The current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days. Results We found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence. Conclusions These data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood. Implications These studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic “spice” cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.

2013 ◽  
Vol 91 (8) ◽  
pp. 640-647 ◽  
Author(s):  
Veronika Ledvenyiova ◽  
Dezider Pancza ◽  
Jana Matejiková ◽  
Miroslav Ferko ◽  
Iveta Bernatova ◽  
...  

Sex and aging represent important factors that determine morbidity and mortality due to cardiovascular diseases in the human population. This study aimed to investigate the impact of aging on the response to ischemia–reperfusion in male and female rat hearts, and to explore a potential role of the PI3K–Akt pathway in the cardioprotective effects of ischemic preconditioning (IPC) in the myocardium of younger and older adult males and females. Langendorff-perfused nonpreconditioned and preconditioned hearts of 12- and 18-week-old male and female Wistar rats were subjected to regional ischemia and reperfusion with or without prior perfusion with the PI3K inhibitor wortmannin for the evaluation of ischemia-induced arrhythmias and the size of myocardial infarction (infarct size; IS). Aging did not modify IS in both sexes; however, it markedly increased susceptibility to arrhythmias. Although IPC effectively reduced IS in males and females of both ages, only the hearts of males and 18-week-old females benefited from its antiarrhythmic effect. In the preconditioned 12-week-old females, but not the 18-week-old females, and in males of both ages, wortmannin blunted the anti-infarct effect of IPC. In conclusion, activation of the PI3K–Akt pathway plays an important role in protection against lethal injury conferred by IPC in males irrespective of age. The IS-limiting effect of IPC appears to be PI3K–Akt-dependent only in the 12-week-old females.


2021 ◽  
pp. 026988112199688
Author(s):  
Eduardo R Butelman ◽  
Caroline Baynard ◽  
Bryan D McElroy ◽  
Thomas E Prisinzano ◽  
Mary Jeanne Kreek

Background: Novel short-acting κ(kappa)-opioid receptor selective antagonists are translational tools to examine the impact of the κ-receptor/dynorphin system in assays related to central nervous system dysfunction (e.g., substance use disorders, anhedonia and depression). The effects of such compounds have been compared in males and females under very limited conditions. Aims: The goal of this study was to examine potential sex differences in the effects of a κ-agonist and a short-acting κ-antagonist in an ethologically relevant test of anhedonia, the “splash test” of self-grooming, and also in the forced swim test and in locomotor activity. Methods: We examined the dose-dependence of grooming deficits caused by the κ-agonist U50,488 (0.1–3.2 mg/kg intraperitoneal (i.p.)) in gonadally intact adult male and female C57BL/6J mice. We then compared the effects of the short-acting κ-antagonist LY2795050 ((3-chloro-4-(4-(((2S)-2-pyridin-3-ylpyrrolidin-1-yl)methyl) phenoxy)benzamide)); 0.032–0.1 mg/kg i.p.) in blocking grooming deficits caused by U50,488 (3.2 mg/kg). The effects of LY2795050 were also studied in the forced swim test (FST). The effects of LY2795050 in blocking the locomotor depressant effects of U50,488 (10 mg/kg) were also studied. Results: U50,488 produced dose-dependent grooming deficits in male and female mice, and LY2795050 prevented these effects. In contrast, LY2795050 decreased immobility in the FST in males at a dose of 0.1 mg/kg, but not in females, up to a dose of 0.32 mg/kg. Also, LY2795050 (0.32 mg/kg) prevented and also reversed the locomotor-depressant effects of U50,488 (10 mg/kg), in males and females. Conclusions: This study further implicates the κ-receptor system in ethologically relevant aspects of anhedonia, and confirms sexual dimorphism in some behavioral effects of novel κ-antagonists.


1983 ◽  
Vol 11 (1) ◽  
pp. 23-28 ◽  
Author(s):  
Frank J. Prerost

Considering the relaxation of sex role restraints and the convergence of male/female reactions to erotica, this study examined the impact of humorous sexual stimuli on adult males and females. Results showed the importance of personal sexual experience and enjoyment with sexual expression on the reactions to sexual humor. Sexist ideas within sexual humor was a significant factor in influencing female appreciation of sexual jokes. Yet some females, depending on life experiences, evidenced cross-sex attitudes in humor preferences.


1967 ◽  
Vol 56 (1) ◽  
pp. 165-176 ◽  
Author(s):  
Donald C. Johnson

ABSTRACT Ventral prostates in hypophysectomized male parabiotic partners of intact animals were used to compare the amount of plasma luteinizing hormone (LH) in males and females of various ages. Ovarian weight, histology, and augmentation with chorionic gonadotrophin, in hypophysectomized androgenized females were used to estimate plasma follicle stimulating hormone (FSH) activity in intact adult males and females. In young animals, up to 50 days of age, males apparently have the same amount of plasma LH as females, but older cyclic females produced significantly heavier prostates in their hypophysectomized male partners than did males. The results are consistent with the interpretation that cyclic surges of LH added to a tonic level produced an average value higher for females than males. In contrast, males of all ages and particularly adults, have a significantly greater amount of circulating FSH than females.


2012 ◽  
Vol 102 (4) ◽  
pp. 453-460 ◽  
Author(s):  
M. Gołębiowski ◽  
M. Paszkiewicz ◽  
A. Grubba ◽  
D. Gąsiewska ◽  
M.I. Boguś ◽  
...  

AbstractThe composition of cuticular and internal n-alkanes in Lucilia sericata larvae, pupae, and male and female imagines were studied. The cuticular and internal lipid extracts were separated by HPLC-LLSD, after which the hydrocarbon fraction was identified by GC/MS in selected ion monitoring (SIM) and total ion current (TIC) modes.The cuticular lipids of the larvae contained seven n-alkanes from C23 to C31. The major n-alkane in L. sericata larvae was C29 (42.1%). The total cuticular n-alkane content in the cuticular lipids was 31.46 μg g−1 of the insect body. The internal lipids of L. sericata larvae contained five n-alkanes ranged from C25 to C31. The most abundant compound was C27 (61.71 μg g−1 of the insect body). Eighteen n-alkanes from C14 to C31 were identified in the cuticular lipids of the pupae. The most abundant n-alkanes ranged from C25 to C31; those with odd-numbered carbon chains were particularly abundant, the major one being C29:0 (59.5%). Traces of eight cuticular n-alkanes were present. The internal lipids of L. sericata pupae contained five n-alkanes, ranging from C25 to C31. The cuticular lipids of female imagines contained 17 n-alkanes from C12 to C30. Among the cuticular n-alkanes of females, C27 (47.5%) was the most abundant compound. Four n-alkanes, with only odd-numbered carbon chains, were identified in the internal lipids of females. The lipids from both sexes of L. sericata had similar n-alkane profiles. The cuticular lipids of adult males contained 16 n-alkanes ranging from C13 to C31. C27 (47.9%) was the most abundant cuticular n-alkanes in males. The same n-alkanes only with odd-numbered carbon chains and in smaller quantities of C27 (0.1%) were also identified in the internal lipids of males.The highest amounts of total cuticular n-alkanes were detected in males and females of L. sericata (330.4 and 158.93 μg g−1 of the insect body, respectively). The quantities of total cuticular alcohols in larvae and pupae were smaller (31.46 μg g−1 and 42.08 μg g−1, respectively). The internal n-alkane contents of larvae, pupae, and male and female imagines were significantly higher than the cuticular n-alkane contents (153.53, 99.60, 360.06 and 838.76 μg g−1 of the insect body, respectively).


2018 ◽  
Author(s):  
A Matzeu ◽  
L Terenius ◽  
R Martin-Fardon

AbstractBackgroundDespite considerable efforts, few drugs are available for the treatment of alcohol (ethanol [EtOH]) use disorders (AUDs). Ethanol directly or indirectly modulates several aspects of the central nervous system, including neurotransmitter/neuromodulator systems. Relapse vulnerability is a challenge for the treatment of EtOH addiction. Ethanol withdrawal symptoms create motivational states that lead to compulsive EtOH drinking and relapse even after long periods of abstinence. Among the therapeutics to treat AUDs, naltrexone (NTX) is a pharmacological treatment for relapse. The goal of the present study was to evaluate the effect of NTX on EtOH drinking in EtOH-dependent male and female rats during abstinence.MethodsWistar rats (males and females) were first trained to orally self-administer 10% EtOH. Half of them were then made dependent by chronic intermittent EtOH (CIE) vapor exposure, and the other half were exposed to air. Using this model, rats exhibit somatic and motivational signs of withdrawal. At the end of EtOH vapor (or air) exposure, the rats were tested for the effects of NTX (10 mg/kg, p.o.) on EtOH self-administration at three abstinence time points: acute abstinence (8 h, A-Abst), late abstinence (2 weeks, L-Abst), and protracted abstinence (6 weeks, P-Abst).ResultsNTX decreased EtOH intake in nondependent rats, regardless of sex and abstinence time point. In post-dependent rats, the effects of NTX improved with a longer abstinence time (i.e., L-Abst and P-Abst) in males, whereas it similarly reduced EtOH drinking in females at all abstinence points.ConclusionsThe data suggest that the therapeutic efficacy of NTX depends on the time of intervention during abstinence and sex. The data further suggest that EtOH dependence induces different neuroadaptations in male and female rats, reflected by differential effects of NTX. The results underscore the significance of considering the duration of EtOH abstinence and sex for the development of pharmacotherapeutic treatments for AUD.


2018 ◽  
Author(s):  
Munmun Chowdhury ◽  
Chun-Feng Li ◽  
Zhen He ◽  
Yuzhen Lu ◽  
Xusheng Liu ◽  
...  

AbstractThe Drosophila melanogaster Toll-Spätzle pathway plays an important role in development and immunity. Drosophila genome encodes nine Toll receptors and six Spätzle (Spz) proteins, and only the canonical Toll-Spz (Toll-1-Spz-1) pathway has been well investigated. In this study, we compared the nine Drosophila Tolls and showed that similarly to Toll, Toll-7 also strongly activated drosomycin promoter. Importantly, we showed that both Toll and Toll-7 interacted with Spz, Spz-2 and Spz-5, and co-expression of Toll or Toll-7 with Spz, Spz-2 and Spz-5 activated the drosomycin promoter. Furthermore, Toll and Toll-7 both recognized vesicular stomatitis virus (VSV) by binding to the VSV glycoprotein. Septic infection in Toll and Toll-7 mutant flies suggested that Toll and Toll-7 differentially affected defense responses in adult males and females after systemic infection by Enterococcus faecalis, Pseudomonas aeruginosa, Candida albicans or VSV. Our results suggest multiple Toll family members activate the expression of antimicrobial peptides. Our results also provide evidence that Toll and Toll-7 bind multiple Spätzle proteins and differentially affect immune defense against different pathogens in adult male and female flies.


2016 ◽  
Vol 43 (5) ◽  
pp. 380 ◽  
Author(s):  
Vernon C. Bleich ◽  
Jericho C. Whiting ◽  
John G. Kie ◽  
R. Terry Bowyer

Context Little is known about the consequences of sexual segregation (differential use of resources by the sexes outside of the mating season) for the conservation of large mammals. Roadways (i.e. the strip of land over which a road or route passes) are ubiquitous around the world, and are a major cause of wildlife mortality, as well as habitat loss and fragmentation. Many populations of bighorn sheep (Ovis canadensis) occur at low densities and in a metapopulation structure. Roadways could affect movements of males and females differentially, an outcome that has not been considered previously. Aims We investigated the propensity of the sexes to cross a paved two-lane road and a single-lane, maintained dirt route and predicted that adult males, because of their life-history characteristics, would cross those roadways more often than females. Methods We investigated movements of male and female bighorn sheep from 1986 to 1990. We used a fixed-wing aircraft with an H-antenna on each wing strut to locate individuals each week from October 1986 to December 1990. We estimated the degree of overlap among 50% core areas of use by males and females with the utilisation distribution overlap index (UDOI). Key results We relocated male and female bighorn sheep on 948 occasions during sexual aggregation and on 1951 occasions during sexual segregation. More males than females were likely to cross both types of roadways during segregation, and the dirt route during aggregation. Propensity of males and females to cross roadways was strongly influenced by time of year (i.e. whether the period of sexual aggregation or sexual segregation). The lowest overlap in 50% core areas was between females and males during periods of segregation (UDOI = 0.1447). Conclusions More males than females crossed Kelbaker Road and the unnamed dirt route during segregation, as well as the unnamed route during aggregation. Both of those features could affect males more than females, and could result in reductions in the use of habitat or increased mortality of bighorn sheep from vehicle collisions as a result of spatial segregation of the sexes. Implications During environmental review, biologists should consider sexual segregation when assessing potential anthropogenic effects on movements of bighorn sheep. Biologists also should consider sexual segregation and how roadways, even lightly traveled routes, affect movements of male and female ungulates differently before manipulating habitat, translocating animals, or constructing or modifying roadways.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A59-A59
Author(s):  
Andrea Gail Marshall ◽  
Jennifer E Norman ◽  
Michael S Chementi ◽  
John C Rutledge ◽  
Sue C Bodine

Abstract Background: As obesity and Type II Diabetes rise globally, it is important to understand the similarities and differences in the response of metabolic tissues between males and females. We wanted to evaluate the impact of prolonged diet induced obesity (DIO) on the skeletal muscle transcriptome of our MuRF1 KO (KO) mice. Methods: RNA was isolated from the gastrocnemius muscle of male and female WT and KO mice that were fed either standard chow (Envigo 2918) or a 45% HFD (Research Diets D12451) for 22 weeks (n = 4). RNA was enriched for mRNA prior to library preparation. RNA sequencing was performed using 150 bp paired-end reads (~ 31.6 M reads per sample). Differentially expressed genes (DEGs) were identified using DESeq2 with an FDR set to 5%. Results: At baseline (chow diet), both male and female KO mice had DEGs compared to their WT counterparts (male, 1174; female, 105). Most DEGs were found to be unique by sex (male, 1151; female, 82), though 23 genes were found to be changed in common. After obesity was induced by 22 weeks of 45% HFD feeding, KO animals showed a greater transcriptional response than their WT counterparts. Males had 1821 DEGs (v. 179 in WT) while females had 4425 DEGs (v. 2090 in WT). In males, 78 genes were changed in common between WT and KO in response to DIO, with 76 of those genes changing in the same direction (Slc282a and Gm15427 did not). In females, 1445 genes were changed in common between WT and KO, with all but 2 genes (Pla2g7 and Zfp385b) changing in the same direction. In both male and female KO animals, oxidative phosphorylation and ribosomal pathways were most significant, though the direction of change in the DEGs was opposite. Conclusion: In skeletal muscle, sex highly influences the genes and pathways changed in response to DIO. Even among common pathways identified, the response between males and females differed. Loss of MuRF1 results in common and unique transcript changes in and between males and females under normal conditions and in DIO.


2018 ◽  
Vol 10 (15) ◽  
pp. 12990-12994
Author(s):  
Suvarna S. Khadakkar ◽  
Ashish D. Tiple ◽  
Arun M. Khurad

Immature stages of Scaptodera rhadamistus (Fabricius) are described for the first time along with notes on nidification and biology.  The larvae differ from other Scarabaeinae species in the structure of raster on tenth sternum with two irregular bunches of serrations ventrally one on either half.  Pupae with pronotum transverse having rounded margins resemble adults, and consist of four lateral, single caudal and single pteronotal support projection.  Adult males and females differ in coloration, structure of pronotum, presence of spine like process on mesosternum and, in the structure of male and female genitalia.


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