Squirrel monkeys were trained to press a key under a multiple schedule of food presentation. In the presence of either
green or red stimulus lights, the 30th response produced a food pellet (fixed-ratio schedule). In the presence of the red stimulus lights (punishment component), the first response of each fixed-ratio produced either an i.v. injection of
histamine [30.0-100.0 micrograms/kg/injection (inj)] or saline, accompanied by a 200-msec presentation of
amber stimulus lights. Sessions in which
histamine was injected alternated with sessions in which saline was injected. Another group of subjects was studied under identical schedule conditions except that electric
shock was scheduled with the 200-msec stimulus light. During alternate sessions, electric
shock at a high or low intensity with the stimulus, or the stimulus alone was scheduled. When performances stabilized,
histamine or high intensity electric
shock selectively suppressed responding in the punishment component; saline, low intensity electric
shock or the stimulus light alone had no effects. Subsequently, different doses of
histamine, I-
nicotine,
cocaine or
beta-carboline-3-carboxylic acid ethyl ester (
beta-CCE) were substituted for
histamine during single sessions.
Histamine (17.8-100 micrograms/kg/inj), I-
nicotine (32 micrograms/kg/inj) and
beta-CCE (10-56 micrograms/kg/inj), but not
cocaine (10.0-100.0 micrograms/kg/inj), produced a dose-related selective suppression of responding similar to that obtained with electric
shock, suggesting that the drugs were functioning as punishers. Punishment by
beta-CCE was antagonized with the
benzodiazepine antagonist,
flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)