TY - JOUR
T1 - Convergence of Reinforcing and Anhedonic Cocaine Effects in the Ventral Pallidum
AU - Creed, Meaghan
AU - Ntamati, Niels R.
AU - Chandra, Ramesh
AU - Lobo, Mary Kay
AU - Lüscher, Christian
N1 - Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/10/5
Y1 - 2016/10/5
N2 - Addiction is a disorder of behavioral symptoms including enhanced incentive salience of drug-associated cues, but also a negative affective state. Cocaine-evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc), drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as a site of convergence of medium spiny neurons expressing dopamine (DA) receptor type 1 (D1-MSNs) and type 2 (D2-MSNs) of the NAc. Repeated in vivo cocaine exposure potentiated output of D1-MSNs, but weakened output of D2-MSNs, occluding LTP and LTD at these synapses, respectively. Selectively restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates opposing behavioral symptoms; targeting the VP may provide novel therapeutic strategies for addictive disorders.
AB - Addiction is a disorder of behavioral symptoms including enhanced incentive salience of drug-associated cues, but also a negative affective state. Cocaine-evoked synaptic plasticity in the reward system, particularly the nucleus accumbens (NAc), drives drug-adaptive behavior. However, how information is integrated downstream of the NAc remains unclear. Here, we identify the ventral pallidum (VP) as a site of convergence of medium spiny neurons expressing dopamine (DA) receptor type 1 (D1-MSNs) and type 2 (D2-MSNs) of the NAc. Repeated in vivo cocaine exposure potentiated output of D1-MSNs, but weakened output of D2-MSNs, occluding LTP and LTD at these synapses, respectively. Selectively restoring basal transmission at D1-MSN-to-VP synapses abolished locomotor sensitization, whereas restoring transmission at D2-MSN-to-VP synapses normalized motivational deficits. Our results support a model by which drug-evoked synaptic plasticity in the VP mediates opposing behavioral symptoms; targeting the VP may provide novel therapeutic strategies for addictive disorders.
UR - http://www.scopus.com/inward/record.url?scp=84992735518&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2016.09.001
DO - 10.1016/j.neuron.2016.09.001
M3 - Article
C2 - 27667004
AN - SCOPUS:84992735518
SN - 0896-6273
VL - 92
SP - 214
EP - 226
JO - Neuron
JF - Neuron
IS - 1
ER -