An investigation of interactions between hypocretin/orexin signaling and glutamate receptor surface expression in the rat nucleus accumbens under basal conditions and after cocaine exposure

Ainhoa Plaza-Zabala, Xuan Li, Mike Milovanovic, Jessica A. Loweth, Rafael Maldonado, Fernando Berrendero, Marina E. Wolf

Research output: Contribution to journalArticle

4 Scopus citations


Hypocretin peptides are critical for the effects of cocaine on excitatory synaptic strength in the ventral tegmental area (VTA). However, little is known about their role in cocaine-induced synaptic plasticity in the nucleus accumbens (NAc). First, we tested whether hypocretin-1 by itself could acutely modulate glutamate receptor surface expression in the NAc, given that hypocretin-1 in the VTA reproduces cocaine's effects on glutamate transmission. We found no effect of hypocretin-1 infusion on AMPA or NMDA receptor surface expression in the NAc, measured by biotinylation, either 30. min or 3. h after the infusion. Second, we were interested in whether changes in hypocretin receptor-2 (Hcrtr-2) expression contribute to cocaine-induced plasticity in the NAc. As a first step towards addressing this question, Hcrtr-2 surface expression was compared in the NAc after withdrawal from extended-access self-administration of saline (control) versus cocaine. We found that surface Hcrtr-2 levels remain unchanged following 14, 25 or 48 days of withdrawal from cocaine, a time period in which high conductance GluA2-lacking AMPA receptors progressively emerge in the NAc. Overall, our results fail to support a role for hypocretins in acute modulation of glutamate receptor levels in the NAc or a role for altered Hcrtr-2 expression in withdrawal-dependent synaptic adaptations in the NAc following cocaine self-administration.

Original languageEnglish (US)
Pages (from-to)101-106
Number of pages6
JournalNeuroscience Letters
Issue numberPB
StatePublished - Dec 17 2013



  • Cocaine
  • Glutamate receptor
  • Hypocretin
  • Nucleus accumbens
  • Orexin
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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