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,

Tamoxifen and mifepriston modulate nicotine induced conditioned place preference in female rats

WOS: 000289958600009PubMed ID: 21272620An increasing number of studies suggest that nicotine/tobacco addiction is modulated by ovarian hormones. The levels of estrogen and progesterone appear to be important in the success of quit attempts and smoking cessation. In women smokers with the diagnosis or risk of breast cancer, the estrogen receptor modulator tamoxifen (TAM) is widely used, and even though the detrimental health effects of smoking are known, this vulnerable group has difficulty quitting and continues to smoke. The current study tested the effect of the estrogen receptor modulator TAM and the progesterone receptor antagonist mifepriston (RU486) on nicotine-induced conditioned place preference (CPP) in adult female rats. A three chambered CPP apparatus was used and nicotine was paired with the initially non-preferred chamber. Rats received nicotine or saline and hormone receptor modulators (vehicle, TAM, RU486) in a 2 x 3 experimental design. We have previously shown that nicotine induces CPP in male Sprague-Dawley rats but not in females. Our results show that while nicotine alone does not induce CPP in female rats, rats treated with TAM exhibit nicotine-induced CPP. Although RU486 has an aversive effect when applied alone, this is ameliorated by nicotine. These results confirm the role of ovarian hormone receptors in nicotine-induced CPP and may have clinical implications for developing more efficient smoking cessation approaches in women smokers. (C) 2011 Elsevier Inc. All rights reserved.Ege UniversityEge University [2006-BAM-02]This work was supported by Ege University Research Fund (Grant Number: 2006-BAM-02)

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

Smoking modulates language lateralization in a sex-specific way

WOS: 000285668200003PubMed ID: 20951712Smoking affects a widespread network of neuronal functions by altering the properties of acetylcholinergic transmission. Recent studies show that nicotine consumption affects ascending auditory pathways and alters auditory attention, particularly in men. Here we show that smoking affects language lateralization in a sex-specific way. We assessed brain asymmetries of 90 healthy, right-handed participants using a classic consonant-vowel syllable dichotic listening paradigm in a 2 x 3 experimental design with sex (male, female) and smoking status (non-smoker, light smoker, heavy smoker) as between-subject factors. Our results revealed that male smokers had a significantly less lateralized response pattern compared to the other groups due to a decreased response rate of their right ear. This finding suggests a group-specific impairment of the speech dominant left hemisphere. In addition, decreased overall response accuracy was observed in male smokers compared to the other experimental groups. Similar adverse effects of smoking were not detected in women. Further, a significant negative correlation was detected between the severity of nicotine dependency and response accuracy in male bur not in female smokers. Taken together, these results show that smoking modulates functional brain lateralization significantly and in a sexually dimorphic manner. Given that some psychiatric disorders have been associated with altered brain asymmetries and increased smoking prevalence, nicotinergic effects need to be specifically investigated in this context in future studies. (C) 2010 Elsevier Ltd. All rights reserved.DFGGerman Research Foundation (DFG) [Gu227/11]; DAADDeutscher Akademischer Austausch Dienst (DAAD)This research was supported by the DFG research grant (Gu227/11) and by the DAAD PhD-Net grant. We would also like to thank the participants for contributing their time

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

Cocaine and amphetamine regulated transcript (CART) and the stress response

WOS: 000239673100009PubMed ID: 16822586CART is expressed abundantly in the hypothalamic paraventricular nucleus and locus coeruleus, major corticotropin releasing factor (CRF) and noradrenaline sources, respectively. There is a bidirectional relation between CART and hypothalamo-pituitary-adrenal axis activity. CART stimulates CRF, adrenocorticotropic hormone and glucocorticoid secretion, whereas CRF and glucocorticoids increase the transcriptional activity of the CART gene; adrenalectomy declines CART expression in the hypothalamus. Stress exposure modulates CART expression in hypothalamus and amygdala in rat brain in a region and sex specific manner. CART may be a mediator peptide in the interaction between stress, drug abuse, and feeding. The review discusses the established role of CART as it relates to the stress response. (c) 2006 Published by Elsevier Inc.NCRR NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Center for Research Resources (NCRR) [RR00165]; NIDA NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA00418, 3 R01 DA010732-05S1