title: Opioid self-administration results in cell-type specific adaptations of striatal medium spiny neurons.
abstract: Medium-sized spiny neurons (MSNs), the predominant neuronal population of the striatum, are an integral component of the many cortical and limbic pathways associated with reward-related behaviors. A differential role of the D1 receptor-enriched (D1) MSNs of the striatonigral direct pathway, as compared with the D2 receptor-enriched (D2) MSNs of the striatopallidal indirect pathway, in mediating the addictive behaviors associated with cocaine is beginning to emerge. However, whether opioids, well-known analgesics with euphoric properties, similarly induce dissociable signaling adaptations in these neurons remains unclear. Transgenic mice expressing green fluorescent protein (GFP)-labeled D1 or D2 neurons were implanted with intravenous jugular catheters. Mice learned to self-administer 0.1mg/kg/infusion of the opioid remifentanil during 2h sessions over 13 contiguous days. Thereafter, the electrophysiological properties of D1- and D2-MSNs in the shell region of the nucleus accumbens (NAc) were assessed. We found that prior opioid exposure did not alter the basic membrane properties nor the kinetics or amplitude of miniature excitatory postsynaptic currents (mEPSCs). However, when challenged with the mu opioid receptor (μOR) agonist DAMGO, the characteristic inhibitory profile of this receptor was altered. DAMGO inhibited the frequency of mEPSCs in D1-MSNs from control mice receiving saline and in D2-MSNs from mice exposed to remifentanil or saline, but this inhibitory profile was reduced in D1-MSNs from mice receiving remifentanil. Remifentanil exposure also altered the probability of glutamate release onto D1-, but not D2-MSNs. Together these results suggest a D1-pathway specific effect associated with the acquisition of opioid-seeking behaviors.
authors: Department of Psychology, University of California, Los Angeles, Los Angeles, CA, USA.
authors: Alex S
authors: AS
authors: James
authors: Jane Y
authors: JY
authors: Chen
authors: Carlos
authors: C
authors: Cepeda
authors: Nitish
authors: N
authors: Mittal
authors: James David
authors: JD
authors: Jentsch
authors: Michael S
authors: MS
authors: Levine
authors: Christopher J
authors: CJ
authors: Evans
authors: Wendy
authors: W
authors: Walwyn
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D059330:GABAergic Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology; D009293:Opioid-Related Disorders / Q000503:physiopathology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000378:metabolism; D000077208:Remifentanil; D012646:Self Administration
chemical_list: D009294:Narcotics; D010880:Piperidines; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D049452:Green Fluorescent Proteins; D018698:Glutamic Acid; D000077208:Remifentanil
keywords: Electrophysiology; Intravenous self-administration; Medium spiny neurons; Mice; Mu opioid receptor; Striatum
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