We have many projects in the laboratory, which fall into to three general categories:
The role of cues in drug-taking behavior
A hallmark of addiction is the ability of drug-associated stimuli (“cues”) to instigate drug-taking, even after periods of abstinence. We use a number of conditioning paradigms to determine under which conditions these drug cues acquire the ability to influence behavior. For example, we model drug taking in our laboratory using intravenous and oral self-administration in rats, with a focus on nicotine, cocaine, and alcohol. Among other findings, we have found that nicotine enhances alcohol intake by altering how rats respond to alcohol cues, and have established relationships between the response to food cues, drug cues, impulsivity, and cue-induced relapse.
Behavioral genetics of addiction-related traits
In collaboration with Jerry Richards at the Research Institute on Addictions and Abraham Palmer at the University of Chicago, we are in the process of testing and genotyping 1600 rats on tests of cue responsivity and behavioral regulation, with the goal of generating a ‘map’ of genomic locations that influence these behaviors. As candidate genes emerge from this research, we will conduct a number of follow-up studies examining the precise roles of these genes in addiction. For example, human studies have shown that polymorphisms of the gene encoding the cell-adhesion molecule cadherin-13 (CDH13) are associated with the subjective response to psychostimulants. We are using genetically modified rats to determine whether this gene influences drug-taking in animal models of addiction. For more information on our mapping project see www.ratgenes.org.
Neurobiology of cue-responsivity
A third focus of our laboratory involves determining how different brain circuits underlie the response to food and drug cues. For these projects, we use simple conditioning paradigms in combination with intracranial recordings and manipulations. For example, in one project, we implant 32-channel electrodes into dopamine-containing areas of the brain, and record neural activity as rats are exposed to a variety of cues. In a second project, we are using virally delivered proteins such as channelrhodopsin to determine whether activation of specific circuits can alter the response to food and drug cues. These projects have just begun, thus far we have established the utility of these techniques by showing that rats will work for the stimulation of midbrain neurons, and that these neurons respond to a greater degree in individuals particularly attracted to cues.