@article{harp_martini_rosenow_mesner_johnson_farber_rissman_2022, title={Fentanyl-induced acute and conditioned behaviors in two inbred mouse lines: Potential role for Glyoxalase}, volume={243}, ISSN={["1873-507X"]}, DOI={10.1016/j.physbeh.2021.113630}, abstractNote={An increase in opioid-overdose deaths was evident before the COVID-19 pandemic, and has escalated since its onset. Fentanyl, a highly potent synthetic opioid, is the primary driver of these recent trends. The current study used two inbred mouse strains, C57BL/6 J and A/J, to investigate the genetics of behavioral responses to fentanyl. Mice were tested for conditioned place preference and fentanyl-induced locomotor activity. C57BL/6J mice formed a conditioned place preference to fentanyl injections and fentanyl increased their activity. Neither effect was noted in A/J mice. We conducted RNA-sequencing on the nucleus accumbens of mice used for fentanyl-induced locomotor activity. Surprisingly, we noted few differentially expressed genes using treatment as the main factor. However many genes differed between strains. We validated differences in two genes: suppressor APC domain containing 1 (Sapcd1) and Glyoxalase 1 (Glo1), with quantitative PCR on RNA from the nucleus accumbens and prefrontal cortex (). In both regions A/J mice had significantly higher expression of both genes than did C57BL/6 J. In prefrontal cortex, fentanyl treatment decreased Glo1 mRNA. Glyoxalase 1 catalyzes the detoxification of reactive alpha-oxoaldehydes such as glyoxal and methylglyoxal, is associated with anxiety and activity levels, and its inhibition reduces alcohol intake. We suggest that future studies assess the ability of Glo1 and related metabolites to modify opioid intake.}, journal={PHYSIOLOGY & BEHAVIOR}, author={Harp, Samuel J. and Martini, Mariangela and Rosenow, Will and Mesner, Larry D. and Johnson, Hugh and Farber, Charles R. and Rissman, Emilie F.}, year={2022}, month={Jan} }
 @misc{martini_corces_rissman_2020, title={Mini-review: Epigenetic mechanisms that promote transgenerational actions of endocrine disrupting chemicals: Applications to behavioral neuroendocrinology}, volume={119}, ISSN={["1095-6867"]}, DOI={10.1016/j.yhbeh.2020.104677}, abstractNote={It is our hope this mini-review will stimulate discussion and new research. Here we briefly examine the literature on transgenerational actions of endocrine disrupting chemicals (EDCs) on brain and behavior and their underlying epigenetic mechanisms including: DNA methylation, histone modifications, and non-coding RNAs. We stress that epigenetic modifications need to be examined in a synergistic manner, as they act together in situ on chromatin to change transcription. Next we highlight recent work from one of our laboratories (VGC). The data provide new evidence that the sperm genome is poised for transcription. In developing sperm, gene enhancers and promoters are accessible for transcription and these activating motifs are also found in preimplantation embryos. Thus, DNA modifications associated with transcription factors during fertilization, in primordial germ cells (PGCs), and/or during germ cell maturation may be passed to offspring. We discuss the implications of this model to EDC exposures and speculate on whether natural variation in hormone levels during fertilization and PGC migration may impart transgenerational effects on brain and behavior. Lastly we discuss how this mechanism could apply to neural sexual differentiation.}, journal={HORMONES AND BEHAVIOR}, author={Martini, Mariangela and Corces, Victor G. and Rissman, Emilie F.}, year={2020}, month={Mar} }
 @article{martini_froment_franceschini_pillon_guibert_cahier_mhaouty-kodja_keller_2020, title={Perinatal Exposure to Methoxychlor Affects Reproductive Function and Sexual Behavior in Mice}, volume={11}, ISSN={["1664-2392"]}, DOI={10.3389/fendo.2020.00639}, abstractNote={Numerous chemicals derived from human activity are now disseminated in the environment where their exert estrogenic endocrine disrupting effects, and therefore represent major health concerns. The present study explored whether Methoxychlor (MXC), an insecticide with xenoestrogens activities, given during the perinatal period (from gestational day 11 to postnatal day 8) and at an environmentally dose [20 μg/kg (body weight)/day], would affect reproductive physiology and sexual behavior of the offspring in mice. While MXC exposure did not induce any differences in the weight gain of animals from birth to 4 months of age, a clear difference (although in opposite direction according to the sexes) was observed on the anogenital distance between intact and exposed animals. A similar effect was also observed on preputial separation and vaginal opening, which reflects, respectively, in males and females, puberty occurrence. The advanced puberty observed in females was associated with an enhanced expression of kisspeptin cells in the anteroventral periventricular region of the medial preoptic area. Exposure to MXC did not induce in adult females changes in the estrous cycle or in the weight of the female reproductive tract. By contrast, males showed reduced weight of the epididymis and seminiferous vesicles associated with reduced testosterone levels and seminiferous tubule diameter. We also showed that both males and females showed deficits in mate preference tests. As a whole, our results show that MXC impacts reproductive outcomes.}, journal={FRONTIERS IN ENDOCRINOLOGY}, author={Martini, Mariangela and Froment, Pascal and Franceschini, Isabelle and Pillon, Delphine and Guibert, Edith and Cahier, Claude and Mhaouty-Kodja, Sakina and Keller, Matthieu}, year={2020}, month={Sep} }
 @article{martini_irvin_lee_lynch_rissman_2020, title={Sex chromosome complement influences vulnerability to cocaine in mice}, volume={125}, ISSN={["1095-6867"]}, DOI={10.1016/j.yhbeh.2020.104821}, abstractNote={Women acquire cocaine habits faster and are more motivated to obtain drug than men. In general, female rodents acquire intravenous cocaine self-administration (SA) faster and show greater locomotor responses to cocaine than males. Sex differences are attributed to differences in circulating estradiol. We used the four core genotype (FCG) mouse to ask whether sex chromosome complement influences vulnerability to cocaine's reinforcing and/or locomotor-activating effects. The FCG cross produces ovary-bearing mice with XX or XY genotypes (XXF, XYF) and testes-bearing mice with XX or XY genotypes (XXM, XYM). A greater percentage of gonadal females acquired cocaine SA via infusions into jugular catheters as compared with XYM mice, but XXM mice were not significantly different than any other group. Discrimination of the active versus inactive nose poke holes and cocaine intake were in general greater in gonadal females than in gonadal males. Progressive ratio tests for motivation revealed an interaction between sex chromosomes and gonads: XYM mice were more motivated to self-administer cocaine taking more infusions than mice in any other group. Locomotor responses to cocaine exposure revealed effects of sex chromosomes. After acute exposure, activity was greater in XX than in XY mice and the reverse was true for behavioral sensitization. Mice with XY genotypes displayed more activity than XX mice when given cocaine after a 10-day drug-free period. Our data demonstrate that sex chromosome complement alone and/or interacting with gonadal status can modify cocaine's reinforcing and locomotor-activating effects. These data should inform current studies of sex differences in drug use.}, journal={HORMONES AND BEHAVIOR}, author={Martini, Mariangela and Irvin, Joshua W. and Lee, Christina G. and Lynch, Wendy J. and Rissman, Emilie F.}, year={2020}, month={Sep} }
 @misc{harp_martini_lynch_rissman_2020, title={Sexual Differentiation and Substance Use: A Mini-Review}, volume={161}, ISSN={["1945-7170"]}, DOI={10.1210/endocr/bqaa129}, abstractNote={The organizational/activational hypothesis suggests that gonadal steroid hormones like testosterone and estradiol are important at two different times during the lifespan when they perform two different functions. First steroids "organize" brain structures early in life and during puberty, and in adults these same hormones "activate" sexually dimorphic behaviors. This hypothesis has been tested and proven valid for a large number of behaviors (learning, memory, social and sexual behaviors). Sex differences in drug addiction are well established for both humans and animal models. Previous research in this field has focused primarily on cocaine self-administration by rats. Traditionally, observed sex differences have been explained by the sex-specific concentrations of gonadal hormones present at the time of the drug-related behavior. Studies with gonadectomized rodents establishes an activational role for estradiol which facilitates vulnerability in females, and when estradiol is combined with progesterone, addiction is attenuated. Literature on organizational actions of steroids is sparse but predicts that testosterone, after it is aromatized to estradiol, changes aspects of the neural reward system. Here we summarize these data and propose that sex chromosome complement also plays a role in determining sex-specific drug-taking behavior. Future research is needed to disentangle the effects of hormones and sex chromosome complement, and we propose the four core genotypes mouse model as an effective tool for answering these questions.}, number={9}, journal={ENDOCRINOLOGY}, author={Harp, Samuel J. and Martini, Mariangela and Lynch, Wendy J. and Rissman, Emilie F.}, year={2020}, month={Sep} }
 @article{marraudino_martini_trova_farinetti_ponti_gotti_panzica_2018, title={Kisspeptin system in ovariectomized mice: Estradiol and progesterone regulation}, volume={1688}, ISSN={["1872-6240"]}, DOI={10.1016/j.brainres.2018.03.014}, abstractNote={The kisspeptin system is clustered in two main groups of cell bodies (the periventricular region, RP3V and the arcuate nucleus, ARC) that send fibers mainly to the GnRH neurons and in a few other locations, including the paraventricular nucleus, PVN. In physiological conditions, gonadal hormones modulate the kisspeptin system with expression changes according to different phases of the estrous cycle: the highest being in estrus phase in RP3V and PVN (positive feedback), and in ARC during the diestrus phase (negative feedback). In this work we wanted to study these hormonal fluctuations during the estrous cycle, investigating the role played by progesterone (P) or estradiol (E2), alone or together, on the kisspeptin system. Gonadectomized CD1 female mice were treated with P, E2 or both (E2 + P), following a timing of administration that emulates the different phases of estrous cycle, for two cycles of 4 days. As expected, the two cell groups were differentially affected by E2; the RP3V group was positively influenced by E2 (alone or with the P), whereas in the ARC the administration of E2 did not affect the system. However P (alone) induced a rise in the kisspeptin immunoreactivity. All the treatments significantly affected the kisspeptin innervation of the PVN, with regional differences, suggesting that these fibers arrive from both RP3V and ARC nuclei.}, journal={BRAIN RESEARCH}, author={Marraudino, Marilena and Martini, Mariangela and Trova, Sara and Farinetti, Alice and Ponti, Giovanna and Gotti, Stefano and Panzica, GianCarlo}, year={2018}, month={Jun}, pages={8–14} }