title: Differential role of hypothalamic orexin/hypocretin neurons in reward seeking motivated by cocaine versus palatable food.
abstract: Hypothalamic orexin/hypocretin (Orx/Hcrt) neurons are thought to mediate both food-reinforced behaviors and behavior motivated by drugs of abuse. However, the relative role of the Orx/Hcrt system in behavior motivated by food versus drugs of abuse remains unclear. This investigation addressed this question by contrasting hypothalamic Orx/Hcrt neuronal activation associated with reinstatement of reward seeking induced by stimuli conditioned to cocaine (COC) versus highly palatable food reward, sweetened condensed milk (SCM). Orx/Hcrt neuronal activation in the lateral hypothalamus, dorsomedial hypothalamus and perifornical area, determined by dual c-fos/orx immunocytochemistry, was quantified in rat brains, following reinstatement of reward seeking induced by a discriminative stimulus (S+) conditioned to COC or SCM. The COC S+and SCM S+initially produced the same magnitude of reward seeking. However, over four subsequent tests, behavior induced by the SCM S+decreased to extinction levels, whereas reinstatement induced by the COC S+perseverated at undiminished levels. Following both the first and fourth tests, the percentage of Orx/Hcrt cells expressing Fos was significantly increased in all hypothalamic subregions in rats tested with the COC S+but not rats tested with the SCM S+. These findings point toward a role for the Orx/Hcrt system in perseverating, compulsive-like COC seeking but not behavior motivated by palatable food. Moreover, analysis of the Orx/Hcrt recruitment patterns suggests that failure of Orx/Hcrt neurons in the lateral hypothalamus to respond to inhibitory inputs from Orx/Hcrt neurons in the dorsomedial hypothalamus/perifornical area may contribute to the perseverating nature of COC seeking.
authors: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Rémi
authors: R
authors: Martin-Fardon
authors: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Gabrielle
authors: G
authors: Cauvi
authors: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Tony M
authors: TM
authors: Kerr
authors: Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA, USA.
authors: Friedbert
authors: F
authors: Weiss
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior; D005502:Food; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D008892:Milk; D009042:Motivation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D000068797:Orexins / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D012201:Reward; D012646:Self Administration
chemical_list: D018765:Dopamine Uptake Inhibitors; D000068797:Orexins; D016760:Proto-Oncogene Proteins c-fos; D003042:Cocaine
keywords: cocaine; hypocretin; hypothalamus; natural reward; orexin; relapse