The `opioid epidemic' is one of the most significant health issues facing this country today with rates of opioid-associated deaths up 200% since 2000. This epidemic is also taking its toll on pregnant women and their babies, with an annual average of ~21,000 pregnant women ages 15 to 44 who have misused opioids this past month.  Infants who have been exposed to opioid drugs  exhibit an increased risk of neurological and behavioral consequences.

Norepinephrine (NE) provides excitatory drive onto midbrain dopamine (DA) neurons and modulates responses to dopaminergic drugs, including psychostimulants. Chronic loss of noradrenergic tone impairs DA neuron firing and DA release, leading to compensatory alterations in postsynaptic DA receptor signaling and a paradoxical hypersensitivity to dopaminergic drugs. The goal of this proposal is to identify the molecular and cellular mechanisms underlying the behavioral hypersensitivity to cocaine following chronic inhibition of the NE biosynthetic enzyme, dopamine -hydroxylase (DBH).

The long-term goal of this research project is to understand the role of scaffolding proteins in the regulation ofopioid receptors. Opioids are commonly administered as systemic analgesics to treat acute, chronic, andintractable pain syndromes. However, activation of mu opioid receptors (MOPr) throughout the central nervoussystem produces negative side effects that often contraindicate continued use.

The long-term goal of this research project is to understand the role of scaffolding proteins in the regulation ofopioid receptors. Opioids are commonly administered as systemic analgesics to treat acute, chronic, andintractable pain syndromes. However, activation of mu opioid receptors (MOPr) throughout the central nervoussystem produces negative side effects that often contraindicate continued use.

Alcohol consumption impairs motor coordination, attentional efforts and memory function. Alcohol-impaireddriving accounted in 2013 for ~31% of all traffic accidents resulting in 10,076 fatalities and $59 billion crash-related cost. We propose to study the mechanisms how ethanol affects brain state-dependent neuralsignaling. Brain state-dependent signaling comprises adjustments in cellular and circuit activity to optimizehow the brain processes information in a distinct behavioral context.