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New Grant Awarded! R01 DA058933

We received notification that our R01 on xylazine and fentanyl co-use will be funded by NIDA on June 15, titled “Neurobehavioral mechanisms of xylazine and fentanyl co-use and withdrawal. This grant will determine the behavioral and neurobiological impacts of xylazine adulteration of intravenously self-administered fentanyl in collaboration with Dr. Terry Hinds, Jr., and will utilize his state-of-the-art Pamgene Pamstation to uncover novel targets to reverse overdose.

Publication Alert! Khatri et al., 2023

Khatri, S., Sadek, S., Kendrick Jr., P.T., Bondy, E.O., Hong, M., Pauss, S., Luo, D., Prisinzano, T., Dunn, K.E., Marusich, J.A., Beckmann, J.S., Hinds Jr., T.D., Gipson, C.D. (in press). Xylazine co-use suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is naloxone-resistant in rats. Experimental and Clinical Psychopharmacology

Xylazine, a veterinary anesthetic, is becoming increasingly prevalent in the fentanyl drug supply within the United States, and opioid overdoses are on the rise, which is being attributed to xylazine’s adulteration of fentanyl. This is the first empirical publication demonstrating the impacts of intravenous xylazine on fentanyl self-administration and withdrawal as a function of xylazine dose and sex. This is also the first to quantitatively show that naloxone resistance occurs following xylazine/fentanyl co-use, and that these effects display a sex-specific trajectory whereby females are more susceptible to naloxone insensitivity and enhanced protracted withdrawal symptomatology following acute naloxone administration, which has enormous translational impact.

Congratulations Shailesh!

Welcome new lab members!

This summer, Ashley White, a MD/PhD student will begin her work in the lab funded through the Professional Student Mentored Research Fellowship Program from the University of Kentucky CCTS. We also welcome Ashley Craig, a recent graduate of the University of Kentucky with a major in Neuroscience. Ashley was recently awarded the NIDA Summer Undergraduate Internship to work on neuroimmune mechanisms of nicotine use in the lab this summer. We are so excited to have you both join us!

Ashley White
Ashley Craig

New publication! Maher et al., 2022

Maher, Kipp, Leyrer-Jackson, Khatri, Bondy, Martinez, Beckmann, Hinds, Bimonte-Nelson, & Gipson (2022). Ovarian Hormones Regulate Nicotine Consumption and Accumbens Glutamatergic Plasticity in Female Rats. eNeuro, Jun 27;9(3):ENEURO.0286-21.2022. doi: 10.1523/ENEURO.0286-21.2022.

Abstract

Women report greater cigarette cravings during the menstrual cycle phase with higher circulating levels of 17β-estradiol (E2), which is metabolized to estrone (E1). Both E2 and E1 bind to estrogen receptors (ERs), which have been highly studied in the breast, uterus, and ovary. Recent studies have found that ERs are also located on GABAergic medium spiny neurons (MSNs) within the nucleus accumbens core (NAcore). Glutamatergic plasticity in NAcore MSNs is altered following nicotine use; however, it is unknown whether estrogens impact this neurobiological consequence. To test the effect of estrogen on nicotine use, we ovariectomized (OVX) female rats that then underwent nicotine self-administration acquisition and compared them to ovary-intact (sham) rats. The OVX animals then received either sesame oil (vehicle), E2, or E1+E2 supplementation for 4 or 20 d before nicotine sessions. While both ovary-intact and OVX females readily discriminated levers, OVX females consumed less nicotine than sham females. Further, neither E2 nor E1+E2 increased nicotine consumption back to sham levels following OVX, regardless of the duration of the treatment. OVX also rendered NAcore MSNs in a potentiated state following nicotine self-administration, which was reversed by 4 d of systemic E2 treatment. Finally, we found that E2 and E1+E2 increased ERα mRNA in the NAcore, but nicotine suppressed this regardless of hormone treatment. Together, these results show that estrogens regulate nicotine neurobiology, but additional factors may be required to restore nicotine consumption to ovary-intact levels.

https://pubmed.ncbi.nlm.nih.gov/35697512/