# title
Cheng, Yifeng (2018-12). The Role of Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in the Corticostriatal Circuitry of Alcohol Use Disorder. Doctoral Dissertation.

# abstract
Alcohol use disorder (AUD) changes glutamatergic and -aminobutyric acidergic (GABAergic) neurotransmission in many neuronal populations. The dorsomedial part of the striatum (DMS) and its critical glutamatergic input, prefrontal cortex (PFC), have been strongly associated with AUD. The DMS contains two types of medium spiny neurons (MSNs): dopamine D1 receptor- and D2 receptor-expressing MSNs (D1-MSNs or D2-MSNs), which have been shown oppositely control the reward-seeking behavior. It is unclear how alcohol affects glutamatergic and GABAergic neurotransmission onto D1- and D2-MSNs and how these types of neurons control alcohol-related behavior. Thus, I first examined the effect of adult alcohol drinking on D1- and D2-MSNs and their contributions to the alcohol-drinking behavior of mice. Then, we investigated the causality between synaptic plasticity and alcohol-seeking behavior in adult rats. Lastly, we further tested prenatal alcohol exposure (PAE)-evoked glutamatergic changes in DMS D1-MSNs of adult mice.  In this dissertation study, I first found that adult alcohol exposure distinctly facilitated glutamatergic inputs in D1-MSNs and GABAergic transmission D2-MSNs. I further discovered that in vivo chemogenetic excitation of D1-MSNs or inhibition of D2-MSNs increased voluntary alcohol consumption, whereas inhibition of D1-MSNs or excitation of D2-MSNs reduced this behavior. Then, we found that optogenetically induced long-term potentiation (LTP) at DMS corticostriatal (especially at mPFC→D1-MSNs) synapses produced a long-lasting increase of alcohol-seeking and -drinking behavior in rats, whereas long-term depression (LTD) induction caused a long-lasting decrease on this behavior. Lastly, I found hyperactivity in both juvenile and adult  offspring. Furthermore, I showed that PAE potentiated glutamatergic transmission onto D1-MSNs and increased the dendritic complexity of D1-MSNs in those hyperactive adult offspring. Taken together, my graduate study suggests that adult alcohol exposure selectively strengthens glutamatergic activity in D1-MSNs and enhances GABAergic activity in D2-MSNs. This alcohol-mediated alternation of D1- and D2-MSNs, in turn, contributes to alcohol-drinking behavior. This cell type-specific regulation on alcohol-drinking behavior may due to the fact that glutamatergic synaptic plasticity between mPFC→ D1-MSNs controls alcohol-seeking and -taking behavior. Lastly, PAE affects glutamatergic transmission onto D1-MSNs, indicating a potential mechanism underlying PAE-induced hyperactivity.

# websites[].label
The Role of Dopamine D1 and D2 Receptor-Expressing Striatal Neurons in the Corticostriatal Circuitry of Alcohol Use Disorder