A parametric analysis of punishment frequency as a determinant of the response to chlordiazepoxide in the Vogel conflict test in rats.
The Vogel conflict test has been widely used as a methodology for detecting anxiolytic-like effects of drugs with a broad spectrum of pharmacological activities. Despite widespread acceptance of the Vogel assay as a preclinical predictor of efficacy for anxiolytic-like compounds, detailed parametrics have not been reported on the optimization of this assay to determine how the schedule of reinforcement, the rate of responding and the frequency and temporal distribution of punishing events determine drug effect. The current report documents results of a systematic study of the relationship between number of shocks delivered and efficacy of the prototypical 1,4-benzodiazepine anxiolytic chlordiazepoxide (CDAP) in rats. Under this procedure, water-deprived rats were given access to water and during the later part of this access period, contacts with the drinking tube produced a brief electric shock. CDAP (5-20 mg/kg, i.p.) was first tested under a fixed-ratio 20 response schedule (every 20 th lick produced shock delivered via the sipper tube). CDAP produced dose-dependent increases in punished licking to approximately 275% of control at 20 mg/kg. Increasing the number of shocks during the first ten responses of the punishment component decreased the number of licks made under vehicle control conditions. The frequency of shock delivery produced both quantitative and qualitative changes in the effects of chlordiazepoxide ranging from no effect to 7000% increases in responding. The effects of chlordiazepoxide were dependent both on the control rate of responding and, independently, on the frequency of shock deliveries. Parametric variation under the Vogel conflict test may be useful in comparing the efficacy of novel approaches to the treatment of anxiety disorders.
Gleason
Scott D
SD
Neuroscience Discovery Research, The Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285-0510, USA. Gleason_Scott_D@lilly.com
Witkin
Jeffrey M
JM
D000818:Animals; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003220:Conflict, Psychological; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D008297:Male; D011678:Punishment; D051381:Rats; D017207:Rats, Sprague-Dawley; D012055:Reinforcement Schedule
D006993:Hypnotics and Sedatives; D002707:Chlordiazepoxide