Neurobehavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6.
A series of neurobehavioral testing procedures was used to evaluate the behavioral effects of the pyridinium aldoxime cholinesterase reactivator HI-6 in male Sprague-Dawley rats. These procedures were fixed-ratio (FR) responding, shuttle-box conditioned avoidance response (CAR), conditioned taste aversion (CTA), drinking behavior, open-field exploratory behavior, negative geotaxis, and wire suspension time. Dose-response studies of HI-6 at dose-levels of 25, 50 and 100 mg/kg, or saline (IP) were evaluated. HI-6 disrupted FR responding in a dose-dependent fashion, with significant effects occurring at doses of 50 and 100 mg/kg. The pattern of disruption was characterized by extended periods of nonresponding having an abrupt onset and offset. HI-6 produced CTA in a dose-related manner, with significant effects at doses equal to those that disrupted FR performance. HI-6 did not alter CAR, drinking motivation, exploratory behavior, negative geotaxis, or wire suspension time. These data suggest that there may be a commonality in the underlying mechanism(s) for the disruption in FR performance and the induction of the CTA. This mechanism may relate to the presumed drug-induced adverse internal state inducing the CTA.
Liu
W F
WF
Laboratory of Behavioral Pharmacology and Toxicology, Fourth Research Division, CSIST, Taiwan, R.O.C.
Shih
J H
JH
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002801:Cholinesterase Reactivators / Q000633:toxicity*; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010091:Oximes; D011726:Pyridinium Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D013649:Taste / Q000187:drug effects
D002801:Cholinesterase Reactivators; D010091:Oximes; D011726:Pyridinium Compounds; C022870:asoxime chloride