Wpływ hormonalnej terapii zastępczej oraz tamoxifenu na depresję u szczurów poddanych usunięciu jajników

Objectives: To determine the effects of tamoxifen and hormone replacement therapy in order to assess their role in depressive behavior. Material and Methods: Different protocols of hormone replacement therapies were administered to surgically ovariectomized rats. Intact rats were used for tamoxifen experiments. Properly assigned control groups were used and cognitive processes were studied on animal models of surgical menopause using the Porsolt Forced Swim Test and locomotor activity experiments. Results: In the tamoxifen experiments, an interaction between treatment and days did not reach statistical significance, but indicated a trend in this direction [F(1,26)=3.557, p=0.071]. The number of repeated movements significantly decreased after the Porsolt test (F(1,44) = 8.483, PCel: Określenie wpływu tamoxifenu oraz hormonalnej terapii zastępczej celem oceny ich roli w zachowaniach depresyjnych. Materiał i metody: Różne protokoły hormonalnej terapii zastępczej zastosowano u szczurów poddanych chirurgicznemu usunięciu jajników. Tamoxifen podawano szczurom, których nie operowano. Wykorzystano odpowiednio dobraną grupę kontrolną. Zbadano procesy poznawcze na modelach zwierzęcych z chirurgiczną menopauzą przy pomocy testu Porsolt Forced Swim oraz doświadczeń aktywności ruchowej. Wyniki: W doświadczeniach z tamoxifenem, związek pomiędzy terapią a dniami nie osiągnął statystycznej istotności, ale wykazał trend w tym kierunku [F(1,26)=3,557,p=0,071]. Liczba powtórzeń ruchów istotnie zmniejszyła się po teście Porsolta [F(1,44)=8,483,

Effects of non-steroidal antiinflammatory drugs on D-serine-induced oxidative stress in vitro

WOS: 000308936500007PubMed ID: 22486999Inflammation is deleterious for organs with reduced capacity of regeneration, such as the brain. Recently, studies have focused on investigating the therapeutic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. Excitotoxicity is the pathological process when receptors for the excitatory neurotransmitter glutamate, such as the N-methyl-D-aspartate (NMDA), receptors are overactivated. This process may be involved in neurodegenerative diseases. D-serine is one of the coagonist of NMDA receptors, and increased levels of D-serine are associated with excitotoxicity. In our study, the potential neuroprotective effects of mefenamic acid, acetaminophen, and naproxen sodium were investigated against D-serine-induced oxidative stress in the rat brain in vitro. To show their potential neuroprotective properties, NSAIDs were incubated with D-serine and reactive oxygen species (ROS), malondialdehyde, and protein carbonyl content of the brain after different treatments were measured. Our results demostrate that NSAIDs used in the present study significantly reduced ROS production, lipid peroxidation, and protein oxidation against D-serine treatment.Turkish Scientific and Technological Council (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK); Ege University Scientific Research FoundationEge University [09/ECZ/019]G.A. acknowledges a scholarship for postgraduate students obtained from the Turkish Scientific and Technological Council (TUBITAK).; This study was supported by the Ege University Scientific Research Foundation (project no.: 09/ECZ/019)

Increased alcohol preference and intake in nicotine-preferring rats

Ozturk, Baran/0000-0002-7462-177X; KANIT, LUTFIYE/0000-0001-5160-411X; Pogun, Sakire/0000-0003-1758-2425WOS: 000503677200001PubMed: 31860364Background: Alcohol and tobacco are among the leading substances that are misused together and shared genetic vulnerability is likely. Increased susceptibility to nicotine self-administration has been shown in alcohol-preferring rat-lines. However, a nicotine-preferring (nP) rat-line has not been studied for alcohol preference. Objectives: To evaluate alcohol preference and intake in male and female nP rats. We hypothesized that nP rats and females would drink more ethanol than control rats and males, respectively. Methods: nP rats are being selectively outbred for high oral nicotine intake at Ege University. Seventeen nP (18(th) generation) and 20 naive female and male SD rats, not previously exposed to alcohol or nicotine, were used. Twelve-week-old rats were given intermittent access to 20% ethanol in a 2-bottle-choice-procedure for six weeks. After one week withdrawal, six weeks of oral nicotine self-administration was applied. Results: nP rats drank significantly more ethanol than controls and their preference for ethanol over water was higher. Female rats' ethanol intake was higher than males'. the nP rats' nicotine preference and intake were higher than controls, and they gained less weight. Conclusion: We have shown for the first time that nP rats also have high alcohol intake. Our results support the hypothesis that shared genetic factors may underlie concurrent addiction to nicotine and alcohol and have translational value in understanding their misuse. Considering the increased vulnerability for alcohol use disorder in smokers and sex differences observed, early preventive measures in families with a history of tobacco addiction, specifically targeting female members, could have public health benefits.Ege University Research FundEge University [17 TIP 071]This work was supported by Ege University Research Fund, Number: 17 TIP 071

Bitter taste and nicotine preference: evidence for sex differences in rats

WOS: 000346073600008PubMed ID: 25490608Background: Nicotine affects sensory pathways and an interaction between taste and nicotine preference is likely. In addition to pharmacologic effects, orosensory factors are important in nicotine dependence. Recent evidence suggests a link between taste (notably bitter) receptor genes and nicotine addiction. Objectives: To explore the possible interaction between taste and nicotine preference in rats, including sex as a factor. Methods: Adult male and female Sprague Dawley rats (n = 82) were used in free choice oral intake experiments. In Experiment 1 rats received water from one bottle and one of the taste substances (quinine, sucrose, or saccharine) from the other bottle for 12 days. Following a wash-out period, Experiment 2a was initiated in the same rats. Rats received water from one bottle and nicotine (10 and 20 mg/l) from the other for 12 days. In Experiment 2b, nicotine exposure was continued for four more weeks. Liquid intake and weight were measured at four-day (Experiments 1 and 2a) and one week (Experiment 2b) periods. Results: In female rats, quinine and subsequent nicotine intake were positively correlated and quinine intake and weight gain were negatively correlated. No association was depicted between nicotine consumption and sweet tastants in either female or male animals. Conclusion: The results suggest that bitter taste and nicotine preference are related, but only in female rats. This finding is parallel to observations in human smokers. Our study may be a preliminary step in the search for common genes that underlie nicotine dependence and taste preference.Ege UniversityEge University [2010 BAM 003]This study was supported by Ege University Research Fund Grant 2010 BAM 003. The authors thank Professor Allan C. Collins for helpful comments in the preparation of this manuscript

Nicotine withdrawal in selectively bred high and low nicotine preferring rat lines

WOS: 000352173200015PubMed ID: 25687373Background: We have generated high- and low-nicotine preferring (high-NP, low-NP) rat lines using voluntary oral nicotine intake as the selection criterion. After nine generations, the estimated realized heritability for high intake was 0.26. The aim of the current study is to compare how nicotine withdrawal varies between these two lines. This new analysis would help elucidate if nicotine withdrawal and intake share common genetic mechanisms. Methods: After exposing male and female Sprague Dawley rats (F-8 generation) to six weeks of nicotine exposure, nicotine was withdrawn. Somatic signs of withdrawal, locomotor activity, and weight were measured at 16 and 40 h. One week after withdrawal, resumption of nicotine intake was determined. Results: The High-NP line had higher nicotine intake before and after withdrawal than the Low-NP line. High-NP rats were more active than Low-NP rats, and locomotor activity decreased during withdrawal; this decrease was more pronounced in the High-NP line. High-NP rats gained more weight during withdrawal than Low-NP rats. Escape attempts decreased during withdrawal in all groups, but overall females demonstrated more escape attempts than males. The other somatic signs of withdrawal were higher during withdrawal compared to baseline and more pronounced in females. Conclusions: Selection for nicotine preference affected nicotine intake, locomotion and weight, suggesting the heritability of these traits. However, despite differences in nicotine preference and intake, high-NP and low-NP rats showed similar withdrawal responses: escape attempts decreased and somatic signs increased. Withdrawal responses of females were more pronounced than males suggesting sex differences in the negative affect induced by nicotine withdrawal. The major finding of this novel analysis is showing that nicotine preference does not predict withdrawal symptoms. This finding, together with sex differences observed during withdrawal, may contribute to a better understanding of nicotine dependence and have translational value in developing more effective strategies for smoking cessation. (C) 2015 Elsevier Inc All rights reserved