title: Effects of inhibitory GABA-active neurosteroids on cocaine seeking and cocaine taking in rats.
abstract: BACKGROUND
  Several compounds that potentiate GABA-induced inhibitory currents also decrease stress, anxiety and addiction-related behaviors. Because of the well-established connection between stress and addiction, compounds that reduce stress-induced responses might be efficacious in treating addiction. Since endogenous neurosteroids such as allopregnanolone may function in a manner similar to benzodiazepines to reduce HPA axis activation and anxiety following stressful stimuli, we hypothesized that exogenously applied neurosteroids would reduce cocaine reinforcement in two animal models.
  
  
  METHODS
  Male Wistar rats were trained to self-administer cocaine and food under a concurrent alternating operant schedule of reinforcement. Two separate groups of rats were trained to self-administer cocaine or food pellets and were then exposed to similar cue-induced reinstatement paradigms. Both groups of rats were pretreated with various doses of neurosteroids.
  
  
  RESULTS
  Allopregnanolone and 3α-hydroxy-3β-methyl-17β-nitro-5α-androstane (R6305-7, a synthetic neurosteroid) were ineffective in selectively decreasing cocaine relative to food self-administration. On the other hand, both allopregnanolone and R6305-7 significantly decreased the cue-induced reinstatement of extinguished cocaine seeking, confirmed by one-way ANOVA.
  
  
  CONCLUSIONS
  These results suggest that neurosteroids may be effective in reducing the relapse to cocaine use without affecting ongoing cocaine self-administration.
authors.affiliation: Department of Pharmacology, Toxicology & Neuroscience, Louisiana State University Health Sciences Center, 1501 Kings Highway, Box 33932, Shreveport, LA, 71130, USA, cschm1@lsuhsc.edu.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Schmoutz
authors.forename: Scott P
authors.initials: SP
authors.lastname: Runyon
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Goeders
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology*; D003463:Cues; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D018682:GABA Agents / Q000627:therapeutic use*; D008297:Male; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D018682:GABA Agents; D018377:Neurotransmitter Agents; D003042:Cocaine