Cholinergic drugs and 4-aminopyridine alter hypoxic-induced behavioral deficits.
To test the hypothesis that decreased acetylcholine (ACh) metabolism during hypoxia is behaviorally important, the effects of cholinergic drugs and 4-aminopyridine, an enhancer of ACh release, were examined in hypoxic mice. Chemical hypoxia (150 mg/kg NaNO2) reduced tight rope test scores from 13.2 +/- 0.2 to 2.8 +/- 0.3. 4-Aminopyridine partially reversed the scores of hypoxic mice (7.3 +/- 0.7). Physostigmine improved performance by hypoxic mice (7.9 +/- 0.4) when it was given before NaNO2 and this effect was blocked by pretreatment with atropine (3.5 +/- 0.4) or mecamylamine (2.4 +/- 0.6). Neostigmine (0.002-0.2 mg/kg) was ineffective. Performance also improved if atropine (7.0 +/- 0.5) or mecamylamine (7.2 +/- 0.5) was given before NaNO2. Nicotine (5.5 +/- 0.7) or the muscarinic agonist arecoline (5.4 +/- 0.5) improved performance when given during the hypoxic episode, and when the drugs were combined, the score was even higher (8.2 +/- 1.0). Neither epinephrine (0.002-2.0 mg/kg) nor norepinephrine (0.00002-2.0 mg/kg) improved performance by hypoxic mice. These results suggest that hypoxia produces a behaviorally important impairment of the cholinergic system perhaps through a primary alteration of acetylcholine release.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001115:Arecoline / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D006584:Hexamethonium Compounds; D010277:Parasympathomimetics; D018738:Hexamethonium; D001115:Arecoline; D008464:Mecamylamine; D009538:Nicotine; D001285:Atropine; D010830:Physostigmine; D015761:4-Aminopyridine