Damien Fair, Ph.D., Project Lead
Martin Pike, Ph.D., Co-Lead

One of the limitations in brain related research linked to MA use disorder is the difficulty relating findings from animal models to humans. Human fMRI, because of its ease of use, noninvasive nature, and accessibility, is now widely used to study substance use disorder (SUD). However, understanding how these indirect findings of neural activity from human studies relate to the biological underpinnings of these signals measured with animal models is difficult. To address these issues we will utilize functional connectivity MRI (fcMRI), a specific form of functional imaging defined as the intrinsic covariance of blood oxygen level dependent (BOLD) signals, while participants are at rest. fcMRI is a novel technique that is readily translatable from humans to animals and back again. It is an optimal “bridge measurement” that will allow for the direct comparison of findings in our humans models to the molecular and structural underpinnings of these functional signals in rodent models - maximizing the translational potential and relatability of the human and rodent research as proposed in this center.

We utilize mice selectively bred for high (MAHDR) and low (MALDR) MA intake. MAHDR line mice lack functional TAAR1 and possess multiple characteristics consistent with a high addiction-risk phenotype, including sensitivity to rewarding and resistance to aversive effects of MA. Specifically, we will characterize functional connectivity in MAHDR and MALDR mice in the resting state and after administration of MA (in MA-naïve animals). We will also characterize functional connectivity in WT and TAAR1 KO rats and in MAHDRTaar1m1J/m1J (control) and TAAR1 MAHDR knock-in (MAHDR-Taar1+/+) mice in the resting state and after administration of MA. Last, we will characterize functional connectivity in WT and TAAR1 KO rats after incubation of MA craving.

• Aim 1: To characterize NAc functional connectivity in MAHDR and MALDR mice in the resting state and after administration of MA (in MA-naïve animals).
• Aim 2: To characterize NAc functional connectivity in WT and Taar1-KO rats and in MAHDR-Taar1m1J/m1J (nonfunctional TAAR1) and MAHDR-Taar1+/+ knock-in (functional TAAR1) mice in the resting state and after administration of MA.
• Aim 3: To characterize NAc functional connectivity in WT and Taar1-KO rats after incubation of MA craving.