Some contextual and historical determinants of the effects of chlordiazepoxide on punished responding of rats.
BACKGROUND
A host of factors that modulate the increases produced by benzodiazepines on responding suppressed by punishment have been described. Nonetheless, the necessary and sufficient conditions for the anxiolytic-like activity in this animal model have not been fully delineated.


OBJECTIVE
The present experiments sought to determine the necessity of the reinforcing event (food delivery), the role of the relationship of food delivery to the punishing stimulus, and the prevailing historical context of behavior in determining the effects of chlordiazepoxide (CDAP) from 1 to 17 mg/kg, i.p. on punished responding.


METHODS
Male, Sprague-Dawley rats pressed a lever under a multiple schedule. In the presence of one stimulus, every 30th response produced food and, in the presence of an alternate stimulus, every 10th response produced food, a brief electric shock, or food plus shock. Additionally, the baseline schedule was manipulated to determine antecedent experience that may contribute to the efficacy of CDAP.


RESULTS
Chlordiazepoxide generally produced little or no effect under the FR 30 schedule but increased response rates under the FR 10 schedule when responding produced either food plus shock (to 600% of control) or shock alone (300% of control) but not food alone. The increases produced when shock alone was delivered were eliminated when rats did not have a history of food plus shock pairings. In addition to increasing suppressed responding, CDAP also prevented the suppression in both punished and non-punished response rates that resulted from adding a food plus shock or shock alone contingency.


CONCLUSIONS
Chlordiazepoxide and perhaps benzodiazepines in general have robust efficacy for both reducing response suppression and for preventing its occurrence. This efficacy is modulated by conditions present at the time of drug exposure and by the history of the organism with respect to response contingencies.
Witkin
Jeffrey M
JM
Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285-0510, USA. jwitkin@lilly.com
D000818:Animals; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D005247:Feeding Behavior / Q000187:drug effects; 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