- Ketamine’s rapid and long-lasting antidepressant effects have shown great promise for helping Major Depressive Disorder (MDD) patients with Treatment Resistant Depression (TRD). However, ketamine itself is addictive and little has been done to examine the abuse potential of repeated exposure treatment regimens for TRD. Additionally, most current research has been done in only male subjects and primarily assessed higher doses of ketamine. Depression is twice as prevalent among women as compared to men and clinical studies suggest that women cycle through the stages of addiction at a faster rate than men. Furthermore, our lab previously demonstrated that female rats were more sensitive to ketamine’s antidepressant-like and addictive-like properties, so more research is needed to examine the neuroadaptations that mediate ketamine’s addictive properties in both sexes. As such, my research focuses on understanding the cellular and molecular mechanisms involved in relapse after a period of abstinence. Transgenic Long-Evans rats expressing Cre-recombinase on the promoter regions of either the dopamine receptor dopamine 1a (D1R) or dopamine receptor dopamine 2 (D2R) genes can be targeted by Cre-dependent designer receptor exclusively activated by designer drugs (DREADDs) viruses and infused into the nucleus accumbens (NAc). Using cue-induced reinstatement, an animal model of relapse, we are examining the effects of chemogenetic manipulation of D1R and D2R containing medium spiny neurons (MSNs) in the NAc. We can thus selectively manipulate D1R/D2R MSNs in order to pinpoint the selective neurons mediating ketamine reinstatement.
- Recent Publications
Strong, C. E., Hagarty, D. P., Brea Guerrero, A., Schoepfer, K. J., Cajuste, S., & Kabbaj, M. (2020). Chemogenetic selective manipulation of nucleus accumbens medium spiny neurons bidirectionally controls alcohol intake in male and female rats. Scientific Reports , . Martin JA, Werner CT, Swarup M, Zhong P, Wang Z, Gobira PH, Stewart AF, Zhang J, Erias K, Siemian JN, Hagarty DP, Mueller LE, Neve RL, Li J, Chandra R, Dietz KC, Lobo MK, Gancarz AM, Yan Z, Dietz DM (2019). A novel role for the actin-binding protein drebrin in regulating opiate addiction. Nature Communications, 10:4140. Wright, K. N., Hagarty, D. P., Strong, C. E., Schoepfer, K. J., & Kabbaj, M. (2019). Sex-dependent ketamine addiction-like behavior profile following exposure to chronic mild stress. Chronic Stress, 3:1-12.
Mohamed Kabbaj, Biomedical Sciences