Experimental Protocols for Behavioral Imaging: Seeing Animal Models of Drug Abuse in a New Light

Abstract

Behavioral neuroimaging is a rapidly evolving discipline that represents a marriage between the fields of behavioral neuroscience and preclinical molecular imaging. This union highlights the changing role of imaging in translational research. Techniques developed for humans are now widely applied in the study of animal models of brain disorders such as drug addiction. Small animal or preclinical imaging allows us to interrogate core features of addiction from both behavioral and biological endpoints. Snapshots of brain activity allow us to better understand changes in brain function and behavior associated with initial drug exposure, the emergence of drug escalation, and repeated bouts of drug withdrawal and relapse. Here we review the development and validation of new behavioral imaging paradigms and several clinically relevant radiotracers used to capture dynamic molecular events in behaving animals. We will discuss ways in which behavioral imaging protocols can be optimized to increase throughput and quantitative methods. Finally, we discuss our experience with the practical aspects of behavioral neuroimaging, so investigators can utilize effective animal models to better understand the addicted brain and behavior.

Whole-brain circuit dissection in free-moving animals reveals cell-specific mesocorticolimbic networks

“…Importantly, a recent study showed that light delivery in the absence of optogenetic stimulation induced strong local fMRI responses in the stimulated site (3). To overcome these limitations, we combined designer receptor exclusively activated by designer drug (DREADD) technology (4), which allows remote in vivo control of cell-specific firing (5), together with behavioral imaging using μPET and [ 18 F]fluorodeoxyglucose (FDG) to measure regional brain glucose metabolism, which is a direct marker of brain function (6)(7)(8)(9). This approach, termed DREADD-assisted metabolic mapping (DREAMM), was used to map functional brain anatomy associated with inhibiting the activity of prodynorphin-expressing (Pdyn-expressing) and of proenkephalin-expressing (Penk-expressing) medium spiny neurons (MSNs) in the medial nucleus accumbens shell (NAcSh), highly implicated in neuropsychiatric disorders.…”

Structured tracking of alcohol reinforcement (STAR) for basic and translational alcohol research

“…Indeed, retrospective evaluations of animal disease models indicate the utility of frameworks which explicitly create avenues for researchers to synthesize findings and provide continuity across subfields [16][17][18][19][20][21]. In the absence of purposeful development of methodological solutions, there is a natural tendency for fields to split along basic and translational lines as highly specialized paradigms are pushed towards partially divergent goals: basic investigations require flexibility of experimental design as hypotheses are rapidly tested and revised, while animal models intended for preclinical to clinical translation emphasize standardized protocols to allow comparison of specific outcome measures [22,23]. The tendency for basic experimental studies and preclinical testing to use non-overlapping methodologies, without explicit efforts to integrate conclusions, impedes progress and translation [18,[24][25][26].…”