Current Grant Work:

In general, our lab is interested in the role of neurotransmitters in processing reward and motivation, as well as learning and memory. The main focus of our research is to understand the neural mechanisms underlying drug abuse and dependence. We currently have two research grants from the National Institute on Drug Abuse:

(1) One of the grants aims to understand the role of dopamine and serotonin neurotransmitter systems in motivation to seek cocaine in animals that have a history of cocaine self-administration.

(2) The other grant is aimed at understanding the neural circuitry involved in cocaine-seeking behavior.

Elucidating the neural mechanisms involved in cocaine-seeking behavior in rats will help to understand the biological basis for drug craving, which is a major factor involved in relapse. In human cocaine abusers, craving is triggered by sampling the drug, exposure to drug-associated environmental cues, and stress. Similarly, these events elicit cocaine-seeking behavior in rats.

Dopamine:

Our findings have suggested an important role of dopamine D1 and D3 receptor subtypes in motivation for cocaine. D3 receptors are particularly interesting because they are primarily located in brain regions involved in cocaine reinforcement and we have found an increase in these receptors one month after the last opportunity to self-administer cocaine, a time point at which we have also observed increased motivation to seek cocaine (Neisewander et al, 2004).

Serotonin:

In addition to dopamine receptors, we have found that serotonin (5-HT) receptor subtypes are also involved in modulating cocaine-seeking behavior. For instance, our findings suggest that stimulation of 5-HT2A receptors facilitate cocaine-seeking behavior, whereas stimulation of 5-HT2C receptors inhibit cocaine-seeking behavior. These receptors are known to modulate dopamine release, and therefore, it is possible the effects of serotonin on motivation for cocaine may be mediated, at least in part, through modulation of dopamine release (Burmeister et al., 2004). We plan to test this hypothesis in future experiments.

Cocaine-associated stimuli:

Another important finding from our laboratory is that cocaine-associated cues versus a sample of cocaine itself likely motivate cocaine-seeking behavior via different, but overlapping, neural circuits (Neisewander et al., 2000). Brain regions activated by cocaine-associated cues have also been shown to play an important role in learning and memory. Our laboratory has been investigating the role of learning and memory in drug-seeking behavior and has found that the dorsal hippocampus is involved in learning and memory of the association between the drug experience and the environmental context present during that experience (Meyers et al., 2006). Furthermore, dopamine D1 receptors in the amygdala may play a role in the rewarding effects of cocaine, as well as expression of cocaine-seeking behavior in response to cocaine and cocaine-associated cues (Alleweireldt et al., 2006).

Projects under way:

We are also in process of developing a model for imaging rat brain using fMRI. Other interests of mine that we may pursue in the near future include the influence of social behavior on drug reward, the role of dopamine and serotonin in stress-induced cocaine-seeking behavior, and sex differences and the influence of hormones on cocaine self-administration.