My primary area of interest is in the ventral tegmental area (VTA). This brain area consists of a heterogeneous population of neurons, plays a role in endogenous reward and is affected by many drugs of abuse. My colleague and I have found a novel long-term potentiation (LTP) of GABAergic synapses onto VTA dopaminergic neurons which can be altered by opioids in vitro. My project focuses on the characterization of this inhibitory LTP, and its underlying mechanisms. Additionally, I am interested in defining the molecular mechanisms by which opioids modify the excitability of the VTA neurons through the alterations of GABAergic transmission; and plasticity in the VTA. All experiments will be conducted in midbrain slices of rats using visualized patch clamp recording.
Aim 1 :To characterize the cellular postsynaptic mechanisms underlying the induction of LTPGABA.
Aim 2 :To determine the retrograde signal that travels from the postsynaptic initiating neuron to direct the presynaptic terminal to release more GABA during LTP.
Aim 3 : To explore the effects of opioids on this LTPGABA in vivo. Considering the enormous burden of drug addiction on society, the focus of this research is highly important. Studies such as this will provide a better understanding of how drugs of abuse modulate brain circuitry in a way causing an addict to manifest long-term unwanted behavioral changes. This study could also provide the potential targets for anti-addiction drugs. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DA021973-02
Application #
7423923
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2007-06-01
Project End
2009-02-28
Budget Start
2008-06-01
Budget End
2009-02-28
Support Year
2
Fiscal Year
2008
Total Cost
$40,532
Indirect Cost
Name
Brown University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
001785542
City
Providence
State
RI
Country
United States
Zip Code
02912
Nugent, Fereshteh S; Niehaus, Jason L; Kauer, Julie A (2009) PKG and PKA signaling in LTP at GABAergic synapses. Neuropsychopharmacology 34:1829-42
Nugent, Fereshteh S; Hwong, Alison R; Udaka, Yoko et al. (2008) High-frequency afferent stimulation induces long-term potentiation of field potentials in the ventral tegmental area. Neuropsychopharmacology 33:1704-12
Nugent, Fereshteh S; Kauer, Julie A (2008) LTP of GABAergic synapses in the ventral tegmental area and beyond. J Physiol 586:1487-93
Nugent, Fereshteh S; Penick, Esther C; Kauer, Julie A (2007) Opioids block long-term potentiation of inhibitory synapses. Nature 446:1086-90