Effect of the radioprotector WR-2721 on operant behavior in the rat.
The effect of WR-2721 on performance maintained by a fixed-ratio 20 (FR-20) schedule for water reinforcement was studied in male Sprague-Dawley rats. Graded doses of WR-2721 (range 25-100 mg/kg) were administered IP immediately prior to a 60 min test session. WR-2721 had a dose dependent monotonic disruptive effect on FR responding, with significant effects at doses of 50, 75 and 100 mg/kg. WR-2721 also decreased postsession water consumption, but only one significant effect at the highest dose (100 mg/kg). Both slopes of the dose-response regression line are parallel in effect. These data indicate that WR-2721 may affect drinking motivation, which could disrupt operant performance, and WR-2721 affects motor behavior at lower doses than those that depress "motivation" to drink. The log dose-probit analysis on the all-or-none disruptive pattern of pause of responding observed from cumulative records disclosed that the slope of this regression line (s = 1.11) was also almost identical to that of reinforcer decrement analyzed from graded dose-response relationship (s = 1.14) and shared the same estimated ED50's (58.5 and 55.6 mg/kg, respectively). A preliminary study using a variety of pharmacological interventions was also carried out to ascertain if the general functional gastrointestinal disorders produced by WR-2721 may subserve the behavioral deficits. Subcutaneous pretreatments with various selective, peripherally active, gastroprotective drugs [cimetidine (30 and 60 mg/kg), pirenzepine (5 and 10 mg/kg) and domperidone (1, 5 and 10 mg/kg)] 30 min prior to challenge with WR-2721 at dose of 100 mg/kg, demonstrated that these drugs did not yield any apparent significant attenuative effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Liu
W F
WF
Fourth Research Department, CSIST, Taiwan, R.O.C.
Shih
J H
JH
Lee
J D
JD
Ma
C
C
Lee
S F
SF
Lin
C H
CH
D004999:Amifostine / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D004294:Domperidone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009946:Organothiophosphorus Compounds / Q000009:adverse effects*; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D009946:Organothiophosphorus Compounds; D010890:Pirenzepine; D004294:Domperidone; D002927:Cimetidine; D004999:Amifostine