Description:

The Department of Pharmacology invites you to a guest speaker lecture presented by Daniel McGehee, Ph.D., Associate Professor of Anesthesia & Critical Care at The University of Chicago.

Below is an overview of the seminar as described by Dr. McGehee:

Our lab and others have shown that the excitatory effects of nicotine on brain reward pathways are mediated by both pre- and postsynaptic mechanisms to enhance dopamine transmission. Long-term synaptic plasticity is a key aspect of the persistent effects of the drug, even after a brief exposure. Recent studies have identified independent brain regions that mediate the aversive effects of high nicotine doses, which likely influence the development and maintenance of nicotine addiction. These effects require activation of the medial habenula (MHb) projections to the interpeduncular nucleus (IPN). It is unknown whether the neural pathways downstream of the IPN are independent of, or converge with dopaminergic reward pathways. Using optogenetic approaches, we found a GABAergic projection from the IPN to the laterodorsal tegmental nucleus (LDTg), an area that promotes activation of ventral tegmental area (VTA) dopamine neurons. Optogenetic activation of IPN neurons directly or of the IPN terminals in LDTg result in behavioral avoidance. Nicotine modulates the IPN inputs to LDTg in a concentration-dependent manner. Most strikingly, inhibition of IPN terminals in the LDTg can shift aversion to a high dose of nicotine towards preference. These studies suggest that aversion to nicotine is mediated by inhibition of reward pathways and may help identify more effective treatments for nicotine addiction.