• Chemogenetic Inhibition of Prelimbic Cortex Reduces Habitual Methamphetamine Self-administration

      Christy, David; Horner, Kristen; Dama, Ashitha; Ramesh, Priya (2021)
      Habitual drug use is the continued use of drugs even if the reward is removed or replaced with aversion. This project hypothesizes that habitual drug use will lead to a decrease in Cannabinoid receptor I (CBI) and an increase in Fatty Acid Amide Hydrolase (FAAH) levels. As Methamphetamine (METH) use increases the endocannabinoid release, this might increase the levels of FAAH and decrease the number of cannabinoid receptors to maintain homeostasis. Special receptors called DREADDS, used to prevent the activation of the patch compartment, are infused into the prelimbic cortex that leads to the patch compartment of the rats. Other rats are given a Vehicle (DMSO) during intracranial infusions. Jugular catheters are then inserted to facilitate self-administration of METH. After the self-administration process, the DREADD and DMSO rats are divided further into groups receiving LiCl (aversive stimulus) or saline solution. Immunohistochemistry examines the neurochemical changes in the perfused brain tissue by labelling CBI receptors and FAAH. Initial immunofluorescent staining of CBI was promising. Currently, co-localized staining of CBI and mu-opioid receptors are being performed to draw conclusions about CBI levels between various groups. Since it is difficult to label enzymes such as FAAH, Oleoyl Trifluoromethyl Ketone, an FAAH inhibitor, will be used to determine if FAAH plays a role in long-term depression in the matrix following habitual METH self-administration. Our results also indicate that habitual METH use decreased over time in the DREADD rats during the pre-aversion period. Regardless of whether or not the DMSO rats received LiCl or saline, they preferred to self-administer METH again.