Effect of the radioprotector WR-2721 on operant behavior in the rat

• Published in: Neurotoxicology and teratology Vol. 11; no. 3; p. 199
• Main Authors: Liu, W F, Shih, J H, Lee, J D, Ma, C, Lee, S F, Lin, C H
• Format: Journal Article
• Language: English
• Published: United States 01.05.1989
• Subjects: Amifostine - adverse effects; Animals; Behavior, Animal - drug effects; Cimetidine - pharmacology; Conditioning, Operant - drug effects; Domperidone - pharmacology; Dose-Response Relationship, Drug; Drinking Behavior - drug effects; Male; Motor Activity - drug effects; Organothiophosphorus Compounds - adverse effects; Pirenzepine - pharmacology; Rats; Rats, Inbred Strains
• ISSN: 0892-0362
• DOI: 10.1016/0892-0362(89)90059-7

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.