Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat

Area of Science:

• Neuroscience
• Pharmacology
• Toxicology

Background:

• Acetylcholinesterase inhibitors like soman are potent neurotoxins.
• Understanding soman's effects and potential for tolerance is crucial for safety and therapeutic research.

Purpose of the Study:

• To investigate the effects of intraperitoneal (IP) soman administration on behavior and acetylcholinesterase (AChE) activity in rats.
• To explore the development of tolerance to soman's behavioral effects with chronic IP administration.

Main Methods:

• Rats were trained on a multiple fixed-interval/fixed-ratio schedule of food delivery.
• Soman was administered IP in doses ranging from 10-40 micrograms/kg.
• Behavioral response rates were monitored.
• AChE activity was analyzed in various tissues, including the brain and gastrointestinal tract.

Main Results:

• IP soman suppressed response rates in a dose-dependent manner.
• Chronic weekly administration led to tolerance, but this effect diminished when administration intervals were extended to 2-5 weeks.
• AChE inhibition was primarily localized to the gastrointestinal tract near the injection site.
• No significant inhibition of brain AChE was observed, even at behaviorally effective doses.

Conclusions:

• IP soman administration can suppress behavior without causing widespread central nervous system toxicity.
• The IP route may be a valuable tool for studying chronic effects and tolerance to soman in controlled settings.
• Localized gastrointestinal AChE inhibition suggests a potential mechanism for behavioral suppression distinct from central effects.