scholarly journals Nicotine Self-Administration With Tobacco Flavor Additives in Male Rats

2019 ◽  
Vol 22 (2) ◽  
pp. 224-231 ◽  
Author(s):  
Matthew I Palmatier ◽  
Amanda L Smith ◽  
Ethan M Odineal ◽  
Emily A Williams ◽  
Ashley B Sheppard ◽  
...  

Abstract Introduction Nicotine can robustly increase responding for conditioned reinforcers (CRs), stimuli that acquire reinforcing properties based on association with primary reinforcers. Menthol and licorice are tobacco flavoring agents also found in sweet foods (eg, candy and ice cream), making them putative CRs before they are consumed in tobacco. We sought to determine if intravenous self-administration (IVSA) of nicotine was enhanced by the inclusion of oral tobacco flavor CRs. Methods Menthol (160 or 320 µM) or licorice root extract (0.1% or 1%) were established as CRs (paired with 20% sucrose) or “neutral” stimuli (paired with water) in separate groups. During subsequent IVSA tests, nicotine was delivered in conjunction with oral presentations of the CR. Results In experiment 1, a menthol CR significantly shifted the peak nicotine dose from 15 µg/kg/infusion (Neutral group) to 3.25 µg/kg/infusion (CR group). In experiment 2, a menthol CR significantly increased operant licks for nicotine (3 µg/kg/infusion) relative to control groups. In experiment 3, both licorice and menthol CRs significantly increased operant licks for nicotine (7.5 µg/kg/infusion) relative to an “inactive” sipper. The licorice CR increased nicotine IVSA in proportion to the strength of the flavor, but both menthol concentrations increased nicotine IVSA to a similar extent. Conclusion Tobacco flavor additives with conditioned reinforcing properties promote acquisition of nicotine self-administration at low unit doses and may have robust impact on tobacco consumption when nicotine yield is low. Implications Tobacco flavor additives are found in rewarding foods (eg, ice cream) and gain palatability based on associations with primary rewards (eg, sugar) making them “conditioned reinforcers.” Nicotine increases the motivation for flavor conditioned reinforcers and the present studies show that tobacco flavor additives can interact with nicotine to promote more nicotine self-administration. The interaction between flavors additives and nicotine may promote nicotine exposure and subsequently dependence.

2022 ◽  
Author(s):  
Ryan Drenan ◽  
Xiao-Tao Jin ◽  
Brenton Tucker ◽  
Leanne Thomas ◽  
Noah Walker ◽  
...  

Many tobacco smokers consume nicotine intermittently, but the underlying mechanisms and neurobiological changes associated with intermittent nicotine intake are unclear. Understanding intermittent nicotine intake is a high priority, as it could promote therapeutic strategies to attenuate tobacco consumption. We examined nicotine intake behavior and neurobiological changes in male rats that were trained to self-administer nicotine during brief (5 min) trials interspersed with longer (15 min) drug-free periods. Rats readily adapted to intermittent access (IntA) SA following acquisition on a continuous access (ContA) schedule. Probabilistic analysis of IntA nicotine SA suggested reduced nicotine loading behavior compared to ContA, and nicotine pharmacokinetic modeling revealed that rats taking nicotine intermittently may have increased intake to maintain blood levels of nicotine that are comparable to ContA SA. After IntA nicotine SA, rats exhibited an increase in unreinforced responses for nicotine-associated cues (incubation of craving) and specific alterations in the striatal proteome after 7 days without nicotine. IntA nicotine SA also induced nAChR functional upregulation in the interpeduncular nucleus (IPN), and it enhanced nicotine binding in the brain as determined via [11C]nicotine positron emission tomography. Reducing the saliency of the cue conditions during the 5 min access periods attenuated nicotine intake, but incubation of craving was preserved. Together, these results indicate that IntA conditions promote nicotine SA and nicotine seeking after a nicotine-free period.


2019 ◽  
Vol 22 (11) ◽  
pp. 710-723 ◽  
Author(s):  
Atul P Daiwile ◽  
Subramaniam Jayanthi ◽  
Bruce Ladenheim ◽  
Michael T McCoy ◽  
Christie Brannock ◽  
...  

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.


2013 ◽  
Vol 229 (2) ◽  
pp. 227-234 ◽  
Author(s):  
Emily E. Roguski ◽  
Hao Chen ◽  
Burt M. Sharp ◽  
Shannon G. Matta

2009 ◽  
Vol 16 (1) ◽  
pp. 3-7 ◽  
Author(s):  
Mahmoud Hosseini ◽  
Hojjat Allah Alaei ◽  
Asieh Naderi ◽  
Mohammad Reza Sharifi ◽  
Reza Zahed

Author(s):  
James M. Kasper ◽  
Ashley E. Smith ◽  
Sierra N. Miller ◽  
Ara ◽  
William K. Russell ◽  
...  

Author(s):  
Adeolu Alex Adedapo ◽  
Olusegun A Fagbohun ◽  
Christianah Dawurung ◽  
Ademola Adetokunbo Oyagbemi ◽  
Temidayo Olutayo Omobowale ◽  
...  

Abstract Background Pueraria tuberosa (Willd) D.C. (Fabaceae) tubers are already used in traditional medicine by Ayurvedic physicians for the management of fertility disorders, general weakness, and also as anti-ageing therapies. Other known pharmacological properties include: anti-hyperglycemics, hepatoprotective, anti-hyperlipidemic, diuretic, nutritive, and anti-fertility agents in male rats. Methods The anti-proliferative effect of the aqueous tuberous root extract of Pueraria tuberosa on vascular smooth muscle cells (VSMCs) and Human Colorectal Adenocarcinoma Cell lines (HT-29) was investigated using the Cell Titer 96 MTT Proliferation Assay where the viable cells were seeded at a density of 5 × 104 (100 µL/well). For VSMC, log concentrations of the extract at 200 and 800 µg/mL were added and incubated for 24 and 48 h time points. Incubation of the extract in the presence of vascular endothelial growth factor (VEGF) and ET-1 was also conducted at different times. Concentrations of the extract (200, 400 and 700 µg/mL) were also added and incubated with the HT 29 cell lines for 24, 48 and 72 h time points. The effect of the tuber aqueous extract of the plant on nuclear factor-κB (NF-κB) expression after 2 h was also carried out using immunoblotting technique. Results The result showed that after 24 h, the effect of the extract in the presence of the mitogens and on the VSMC was more of proliferation. However, at 48 h, the 200 µg/mL dose, both alone and in the presence of VEGF caused 11.1% and 25.9% decreases respectively, in cell proliferation. In the HT 29 cytotoxic study the 200 µg/mL concentration caused the greatest cytotoxic effect at 77.1% cell inhibition followed by 400 µg/mL concentration at 71.4% after 72 h. The immunoblotting assay showed a down regulation of NF-κB expressions with 0.7 µg/mL concentration showing the greatest effect. NF-κB, a pro-inflammatory agent is increasingly recognized as a crucial player in many steps of cancer initiation and progression. Conclusions It could therefore be concluded that the aqueous root extract of Pueraria tuberosa possesses cytotoxic effect and could serve as a lead compound for anticancer and anti-inflammatory agents.


2021 ◽  
Vol 10 (2) ◽  
pp. 36
Author(s):  
Alvyan Lantang Anugrah ◽  
Hana Eliyani ◽  
Budi Utomo ◽  
Suherni Susilowati ◽  
Maslichah Mafruchati ◽  
...  

The aim of this research was to know whether beetroot (Beta Vulgaris) extract could protect spermatogenesis by maintaining spermatogenic and sertoli cell count  in rats (Rattus novergicus) induced with CCl4. Rats were given beetroot extract daily, for 14 days and 3ml/kg BW CCl4 intraperitoneally one hour after last treatment. This study used twenty rats which were devided equally into 5 groups. K(-), the negative control group was not induced with CCL4 and only given 1% CMC-Na suspension. K(+), the positive control group was induced with CCl­4 and given 1% CMC-Na suspension. P1, P2 and P3 were given beet root extract with doses of 200, 400, and 800 mg/kg BW daily before feeding. All of the beetroot treatment were given orally (2 ml). After 24 hours CCl4 induction, rats were sacrificed and testis were collected to make histology slides. The observations showed significantly different (p<0,05) in all of variables. Result showed significant differences in spermatogenic and sertoli cells between K(-) and K(+) groups, K(+) with P2 and P3 group, and showed insignificant difference between P2 and P3 group in spermatogenic and sertoli cells. The result of this research showed that beetroot extract could protect the spermatogenic and sertoli cells in male rats induced with CCl4.


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