title: Increased excitability of lateral habenula neurons in adolescent rats following cocaine self-administration.
abstract: BACKGROUND
  The lateral habenula is a brain region that has been critically implicated in modulating negative emotional states and responses to aversive stimuli. Exposure to addictive drugs such as cocaine negatively impacts affective states, an effect persisting longer than acute drug effects. However, the mechanisms of this effect are poorly understood. We hypothesized that drugs of abuse, such as cocaine, may contribute to drug-induced negative affective states by altering the firing properties of lateral habenula neurons, thus changing the signaling patterns from the lateral habenula to downstream circuits.
  
  
  METHODS
  Using whole-cell current-clamp recording of acutely prepared brain slices of rats after various periods of withdrawal from cocaine self-administration, we characterized an important heterogeneous subregion of the lateral habenula based on membrane properties.
  
  
  RESULTS
  We found two major relevant neuronal subtypes: burst firing neurons and regular spiking neurons. We also found that lateral habenula regular spiking neurons had higher membrane excitability for at least 7 days following cocaine self-administration, likely due to a greater membrane resistance. Both the increase in lateral habenula excitability and membrane resistance returned to baseline when tested after a more prolonged period of 45 days of withdrawal.
  
  
  CONCLUSIONS
  This is the first study to look at intrinsic lateral habenula neuron properties following cocaine exposure beyond acute drug effects. These results may help to explain how cocaine and other drugs negatively impact affect states.
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter). pan23@pitt.edu yandong@pitt.edu.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Neumann
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter).
authors.forename: Masago
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter).
authors.forename: Mami
authors.initials: M
authors.lastname: Otaka
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter).
authors.forename: Yanhua H
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter).
authors.forename: Oliver M
authors.initials: OM
authors.lastname: Schlüter
authors.affiliation: Neuroscience Department (Drs Neumann, Ishikawa, Otaka, and Dong), and Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA (Dr Huang); Molecular Neurobiology, European Neuroscience Institute, Göttingen, Germany (Dr Schlüter). pan23@pitt.edu yandong@pitt.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
mesh_terms: D000200:Action Potentials; D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D017097:Electric Impedance; D019262:Habenula / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology* / Q000523:psychology; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D003042:Cocaine
keywords: addiction; cocaine; lateral habenula; membrane excitability; plasticity