Nicotine Addiction

Nicotinic and D1 Dopamine Receptor Interactions in Brain Reward Areas
2008 Seed Grant
Danyan Mao, Ph.D.
University of Chicago

Nicotine is the major addictive substance in tobacco. Its action on the nicotinic receptors in the brain is the initial step that sets off a series of transient and persistent adaptive changes eventually leading to addiction.  Similar to many other drugs of abuse, nicotine exploits the so-called “brain reward pathway” that originates in the ventral tegmental area (VTA) and projects to the limbic and cortical structures in the brain.  By modulating both excitatory and inhibitory inputs, acute nicotine increases excitability and plasticity of the dopaminergic (DA) neurons in the reward circuit crucial to the reinforcing effect of nicotine and a number of other psychostimulants.  Recent findings in our lab have revealed a previously unknown phenomenon in the modulation of the inhibitory input to the DA neurons in the VTA.  D1 dopamine receptor, a subtype of dopamine receptors involved in behavioral sensitization and drug self-administration, tonically modulates the inhibitory input to the DA neuron and, moreover, it is required for the acute nicotinic effect on synaptic transmission to the DA neurons.  We propose to further investigate the interaction between nicotinic receptors and D1 receptor sin the inhibitory synaptic input in the VTA under acute, as well as chronic in vivo exposure of nicotine in adult rats.