Tamoxifen produces conditioned taste avoidance in male rats: An analysis of microstructural licking patterns and taste reactivity

Fudge, Melissa A.; Kavaliers, Martin; Baird, John-Paul; Ossenkopp, Klaus‐Peter

doi:10.1016/j.yhbeh.2009.06.009

Cited by 10 publications

(6 citation statements)

References 69 publications

(105 reference statements)

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“…It is well established that continuous administration of TMX induces a reduction in body weight. [36][37][38][39] Therefore, we measured the body weight of all SCI rats as an indicator of the effectiveness of TMX delivery via pellets. TMX-treated SCI rats had markedly and significantly reduced body weight versus control SCI rats ( Fig.…”

Section: Resultsmentioning

confidence: 99%

The Cancer Drug Tamoxifen: A Potential Therapeutic Treatment for Spinal Cord Injury

Guptarak

Wiktorowicz

Sadygov

et al. 2014

Journal of Neurotrauma

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Tamoxifen (TMX) is a selective estrogen receptor modulator that can mimic the neuroprotective effects of estrogen but lacks its systemic adverse effects. We found that TMX (1 mg/day) significantly improved the motor recovery of partially paralyzed hind limbs of male adult rats with thoracic spinal cord injury (SCI), thus indicating a translational potential for this cancer medication given its clinical safety and applicability and the lack of currently available treatments for SCI. To shed light on the mechanisms underlying the beneficial effects of TMX for SCI, we used proteomic analyses, Western blots and histological assays, which showed that TMX treatment spared mature oligodendrocytes/increased myelin levels and altered reactive astrocytes, including the upregulation of the water channels aquaporin 4 (AQP4), a novel finding. AQP4 increases in TMX-treated SCI rats were associated with smaller fluid-filled cavities with borders consisting of densely packed AQP4-expressing astrocytes that closely resemble the organization of normal glia limitans externa (in contrast to large cavities in control SCI rats that lacked glia limitans-like borders and contained reactive glial cells). Based on our findings, we propose that TMX is a promising candidate for the therapeutic treatment of SCI and a possible intervention for other neuropathological conditions associated with demyelination and AQP4 dysfunction.

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Section: Resultsmentioning

confidence: 99%

The Cancer Drug Tamoxifen: A Potential Therapeutic Treatment for Spinal Cord Injury

Guptarak

Wiktorowicz

Sadygov

et al. 2014

Journal of Neurotrauma

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“…genomic, rather than neurosteroid) effects of estrogen, which are delayed in onset and can persist for long periods after the estrogen peak [see review, 48]. Furthermore, estrogen and estrogen receptor agonist administration decreases food intake in male rats [51]. Collectively, this evidence indicates that testosterone drives food intake for males and females, but has no effect on cocaine intake; while estrogen attenuates motivation for food in males and females, and increases cocaine intake in females only.…”

Section: Role Of Female Reproductive Cycle and Gonadal Hormones On Fomentioning

confidence: 99%

Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms

Kerstetter¹,

Kippin²

2012

J Addict Res Ther

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IntroductionWomen, compared to men, face a more severe pattern of cocaine dependence. Sex differences in the profile of cocaine dependence have indicated that women, relative to men, transition faster from first use to entering treatment [1], which may be explained by women abusing cocaine via more addictive routes more quickly and reporting a more rapid progression of drug dependence [2]. In addition, cocaine dependent women report shorter cocaine-free periods [3], have an increased incidence of relapse [4], experience greater cocaine craving in response to psychological and physical stressors [5], and have a greater tendency to report relapses with an impulsive quality [6]. There is also evidence of sex differences in the profile of dependence on other drugs such as prescription opiates [7] and methamphetamine [8,9] that have indicated a more severe impact of substance abuse in women compared to men, including exacerbation of cognitive impairments associated with stimulant dependence [9]. Compared to cocaine-dependent men, cocaine-dependent women are also more likely to attempt suicide [10,11] and addicted women exhibit poorer nutrition than addicted men [12]. Together, these findings indicate that a critical aspect in sex differences in addiction may include altered evaluation of the choice to engage in drug taking versus nondrug experiences, such as food and other pleasurable activities.Sex differences in psychostimulant dependence may be explained by the effects of gonadal hormones, including fluctuations across the female reproductive cycle. For women, the subjective experience of using cocaine is more or less pleasurable, depending on what phase of the menstrual cycle they are in at the time of drug intake [13,14]. In addition, progesterone administration can diminish the positive effects of cocaine in women, but not men [15,16]. Accordingly, evidence from human laboratory studies indicates that there are roles for hormones in cocaine responsiveness and that the ability of hormones to modulate cocaine responsiveness is sexually differentiated. However, the direction of sex differences in stimulant reinforcement can sometimes be dose-dependent. For instance, one study that AbstractMen and women express sexually dimorphic patterns of cocaine abuse, such that women progress faster from initially trying cocaine to becoming dependent upon the drug and display a greater incidence of relapse. Sex differences in response to cocaine are also seen in the laboratory in both humans and animal models. In this review, animal models of cocaine abuse that have reported sex differences in appetitive reinforcement are discussed. In both human and animal studies, sex differences in the subjective and behavioral effects of cocaine are often related to the female reproductive cycle and ovarian hormones. As a comparison, food reinforcement studies have shown the opposite profile of sex differences and the impact of sex steroids on food intake and response rate. In contrast, limited attention has been given to "choice" models i...

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“…Raloxifene, tamoxifen and genistein are three extensively studied compounds for breast cancer development, prevention and treatment in female ovariectomized rats 11–13 . No studies have been done to clearly understand the effect of diminishing and resurrected levels of estrogen on oral bioavailability of these phenolic compounds in female ovariectomized rats, which could significantly impact their efficacy.…”

Section: Introductionmentioning

confidence: 99%

“…Female ovariectomized rodents with a diminished level of estrogen (a major female sex hormone) have been the model of choice for testing the effectiveness of antiestrogens such as tamoxifen and phytoestrogens such as genistein against breast cancer and bone loss for more than two decades. , Raloxifene, tamoxifen, and genistein are three extensively studied compounds for breast cancer development, prevention, and treatment in female ovariectomized rats. − No studies have been done to clearly understand the effect of diminishing and resurrected levels of estrogen on oral bioavailability of these phenolic compounds in female ovariectomized rats, which could significantly impact their efficacy.…”

Section: Introductionmentioning

confidence: 99%

Effects of Estrogen and Estrus Cycle on Pharmacokinetics, Absorption, and Disposition of Genistein in Female Sprague–Dawley Rats

Kulkarni

Yang

Niu

et al. 2012

J. Agric. Food Chem.

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Genistein is an active soy isoflavone with anticancer activities but it is unknown why it has a higher oral bioavailability in female than in male rats. Our study determined the effects of estrus cycle on genistein’s oral bioavailability. Female rats with various levels of estrogen were orally administered with genistein or used in a four-site rat intestinal perfusion experiment. Rats in “proestrus” group (with elevated estrogen) had significantly reduced (57% decrease, p<0.05) oral bioavailability of total genistein (aglycone+conjugates) than those in “metoestrus” group (with basal level of estrogen). Female ovariectomized rats, due to lack of estrogen, showed oral bioavailability of total genistein similar to the “metoestrus” group but higher (155% increase, p<0.05) than the “proestrus” group. Based on intestinal perfusion studies, the increased bioavailability was partially attributed to the higher (>100% increase, p<0.05) hepatic disposition via glucuronidation and possibly more efficient enterohepatic recycling of genistein in the “metoestrus” group. Furthermore, chronic exogenous supplementation of estradiol in ovariectomized rats significantly reduced (77%, p<0.05) the oral bioavailability of total genistein, mostly via increased sulfation (>10 folds) in liver, to a level comparable to those in the “proestrus” group. In conclusion, the oral bioavailability of total genistein was inversely proportional to elevated estrogen levels in female rats, which is partially mediated through the regulation of hepatic enzymes responsible disposition of genistein.

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Tamoxifen produces conditioned taste avoidance in male rats: An analysis of microstructural licking patterns and taste reactivity

Cited by 10 publications

References 69 publications

The Cancer Drug Tamoxifen: A Potential Therapeutic Treatment for Spinal Cord Injury

The Cancer Drug Tamoxifen: A Potential Therapeutic Treatment for Spinal Cord Injury

Impact of Sex and Gonadal Hormones on Cocaine and Food Reinforcement Paradigms

Effects of Estrogen and Estrus Cycle on Pharmacokinetics, Absorption, and Disposition of Genistein in Female Sprague–Dawley Rats

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