title: Effects of the neuroactive steroid allopregnanolone on intracranial self-stimulation in C57BL/6J mice.
abstract: BACKGROUND
  The neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP, allopregnanolone) has effects on reward-related behaviors in mice and rats that suggest that it may activate brain reward circuits. Intracranial self-stimulation (ICSS) is an operant behavioral technique that detects changes in the sensitivity of brain reward circuitry following drug administration.
  
  
  OBJECTIVE
  To examine the effects of the neuroactive steroid allopregnanolone on ICSS and to compare these effects to those of cocaine.
  
  
  METHODS
  Male C57BL/6J mice implanted with stimulating electrodes implanted into the medial forebrain bundle responded for reinforcement by electrical stimulation (brain stimulation reward (BSR)). Mice received cocaine (n = 11, 3.0-30.0 mg/kg, intraperitoneal (i.p.)) or the neuroactive steroid allopregnanolone (n = 11, 3.0-17.0 mg/kg, i.p.). BSR thresholds (θ 0) and maximum (MAX) operant response rates after drug treatments were compared to those after vehicle injections.
  
  
  RESULTS
  Cocaine and allopregnanolone dose dependently lowered BSR thresholds relative to vehicle injections. Cocaine was maximally effective (80 % reduction) in the second 15 min following the 30 mg/kg dose, while allopregnanolone was maximally effective (30 % reduction) 15-45 min after the 17 mg/kg dose. Neither drug had significant effects on MAX response rates.
  
  
  CONCLUSIONS
  The effects of allopregnanolone on BSR thresholds are consistent with the previously reported effects of benzodiazepines and alcohol, suggesting that positive modulation of GABAA receptors can facilitate reward-related behaviors in C57BL/6J mice.
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Fish
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Buddy J
authors.initials: BJ
authors.lastname: Whitman
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Jeff F
authors.initials: JF
authors.lastname: DiBerto
authors.affiliation: Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: J Elliott
authors.initials: JE
authors.lastname: Robinson
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Departments of Psychiatry and Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Morrow
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.|Department of Neurology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: C J
authors.initials: CJ
authors.lastname: Malanga
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011280:Pregnanolone / Q000494:pharmacology*; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects*
chemical_list: D018377:Neurotransmitter Agents; D011280:Pregnanolone; D003042:Cocaine