The effects of acute administration of gepirone in rats trained on conflict schedules having different degrees of predictability.
The anticonflict activity of gepirone, a putative anxiolytic and antidepressant, was examined on three schedules which conditioned the suppression of licking. The novel schedules differed in the degree to which they predicted (signalled) the presentation of a conflict-inducing electric shock. Three doses of gepirone (1.25, 2.5, and 5 mg/kg SC) were evaluated on a predictable, a moderately predictable, and an unpredictable schedule of shock presentation. Gepirone induced a nondose-dependent increase from baseline in punished licking on the predictable schedule on the last two days of a five-day test period. The lowest dose (1.25 mg/kg) of gepirone induced a significant increase in punished licking on the moderately predictable schedule on the last two days of testing. The highest dose (5 mg/kg) induced initial decreases in overall responding on this schedule. However, responding returned to baseline over the course of the four days of testing. When administered to rats trained on an unpredictable schedule of shock presentation, all doses of gepirone induced an initial decrease from baseline. The lowest dose group returned to baseline control response levels over the next four days, whereas the suppressive effects of the higher doses persisted. The initial decrease in responding observed on all schedules may be due to the effects of gepirone on motor functioning. However, the 2.5-mg/kg dose induced a proconflict or anxiogenic effect on the last test day (decreased punished responding alone) on the unpredictable schedule, while inducing an anticonflict effect on the predictable one. The unpredictable schedule is sensitive to detecting decreases as well as increases in punished responding and as such may be a unique conflict model for evaluating novel anxiolytics.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Albany Medical College, NY 12208.
N L
NL
Costello
J N
JN
Carlson
S D
SD
Glick
M
M
Bryda
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D003213:Conditioning, Psychological; D003220:Conflict, Psychological; D004327:Drinking Behavior; D004597:Electroshock; D005260:Female; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D013997:Time Factors
D014151:Anti-Anxiety Agents; D011743:Pyrimidines; C039979:gepirone