Effects of selected anticholinergics on acoustic startle response in rats.
The present study compared the effects of the anticholinergics aprophen hydrochloride, atropine sulfate, azaprophen hydrochloride, benactyzine hydrochloride, biperiden hydrochloride, diazepam, procyclidine hydrochloride, scopolamine hydrobromide and trihexyphenidyl hydrochloride on acoustic startle response in rats. Peak startle amplitude, latency to peak startle amplitude and prepulse inhibition following 100- and 120-dB tones were recorded 15 min following drug administration in food-restricted rats. Aprophen, atropine, azaprophen, benactyzine, biperiden and scopolamine significantly increased peak startle amplitude and decreased latency to peak startle amplitude following 100-dB pulses. In contrast, only biperiden increased peak startle amplitude following 120-dB pulses, whereas atropine and trihexyphenidyl decreased latency to peak startle amplitude following 120-dB pulses. Benactyzine decreased prepulse inhibition following both 100- and 120-dB pulses, whereas both biperiden and scopolamine decreased prepulse inhibition following 120-dB pulses. Acoustic startle response measures were effective in differentiating the effects of anticholinergic compounds. The comparison of drug effects on the acoustic startle response may be useful in selecting efficacious anticholinergic drug therapies with a minimal range of side-effects. In addition, these data may be useful in down-selecting the number of anticholinergic drugs that need to be tested in comparison studies involving more complex behavioral tests.
Sipos
M L
ML
Advanced Assessment Branch, Drug Assessment Division, US Army Medical Research Institute of Chemical Defense, APG, MD 21010-5400, USA. maurice.sipos@amedd.army.mil
Burchnell
V
V
Galbicka
G
G
D000161:Acoustic Stimulation; D000818:Animals; D002619:Chemical Warfare Agents / Q000633:toxicity; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*
D002619:Chemical Warfare Agents; D018680:Cholinergic Antagonists; D018696:Neuroprotective Agents