People start to take addictive drugs to experience elevation or alteration in mood ("highs"). However, after repeated use of drugs, the drug-seeking and drug-taking behaviors get out of control and become compulsive, which is the defining feature of drug addiction. Dr. Hitoshi Morikawa's lab studies the brain circuits involved in the acute actions of drugs and the plastic changes in the circuits that are responsible for the development of addiction.
This lab specifically focuses on the dopaminergic neurons in the ventral midbrain. They are activated by the perception and expectation of rewards. Therefore, the dopaminergic projections from the midbrain to the limbic structures constitute an endogenous reward circuit. Behaviors that lead to the enhancement of dopamine release in this brain reward circuit tend to be repeated (reinforced). Addictive drugs induce stronger stimulation of dopaminergic transmission than almost any natural reinforcers (food, sex, etc). Thus, drugs are repeatedly used (abused) in vulnerable individuals, which will lead to plastic changes in the reward circuit.
The amount and temporal profile of dopamine release is controlled by the firing pattern of dopamine neurons, which is determined by the interaction of their intrinsic membrane properties and the afferent inputs they receive from other neurons. Accordingly, we make detailed analyses of the influence of addictive drugs on membrane ionic conductances and neurotransmitter inputs of dopamine neurons, and investigate the resulting alteration in the firing pattern. We use brain slices because they retain intact synaptic connections that are necessary for these studies. Brain slices are obtained from drug-naïve animals and animals that are chronically treated with drugs to elucidate the plastic changes induced by repeated exposure to drugs in vivo. Technically, we perform patch clamp electrophysiological recordings combined with confocal fluorescent imaging of intracellular ions. These methods will allow us to delineate the cellular events that determine the excitability of neurons with a preciseness that could not be attained by other conventional techniques. Therefore, this lab offers an ideal system to link the behavior of certain types of central neurons to that of a whole organism.