title: 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.
abstract: 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 3h 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.
authors.affiliation: Laboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, PRBB, C/ Doctor Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Plaza-Zabala
authors.forename: Xuan
authors.initials: X
authors.lastname: Li
authors.forename: Mike
authors.initials: M
authors.lastname: Milovanovic
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Loweth
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Fernando
authors.initials: F
authors.lastname: Berrendero
authors.forename: Marina E
authors.initials: ME
authors.lastname: Wolf
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017470:Receptors, Glutamate; D003042:Cocaine
keywords: Cocaine; Glutamate receptor; Hypocretin; Nucleus accumbens; Orexin; Synaptic plasticity