Cholinergic agents and delay-dependent performance in the rat.
We tested cholinergic agents in delayed matching and nonmatching to position. Each task had a delay between the presentation of information and the chance to act on it later. We used a titrating procedure, new to experiments with rats, to determine the delay. Linopirdine (0.1 mg/kg), which releases acetylcholine, and physostigmine (0.1 mg/kg), a cholinesterase inhibitor, ameliorated the impairment of accuracy produced by scopolamine hydrobromide (0.1 mg/kg). In some cases, scopolamine hydrobromide decreased the number of trials, but physostigmine and linopirdine did not ameliorate that impairment. Both the muscarinic receptor antagonist, scopolamine hydrobromide (0.1 and 0.3 mg/kg), and its peripherally acting analog, scopolamine methylbromide (0.1 and 0.3 mg/kg), decreased accuracy. The impairment produced by scopolamine methylbromide suggests that the deficit produced by muscarinic receptor antagonism may have both a central and peripheral component. At the highest dose, scopolamine hydrobromide decreased the number of trials completed. Thus, some of the effects of scopolamine hydrobromide involve nonmnemonic performance factors. The performance deficits produced by scopolamine hydrobromide suggest that it may be necessary to qualify drug effects in terms of their action on both memorial and nonmemorial aspects of performance.
Buxton
A
A
Department of Neurosciences, Syntex Discovery Research, Palo Alto, CA 94303.
Callan
O A
OA
Blatt
E J
EJ
Wong
E H
EH
Fontana
D J
DJ
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D018678:Cholinergic Agents / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019832:N-Methylscopolamine; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012602:Scopolamine Derivatives / Q000494:pharmacology
D018678:Cholinergic Agents; D007211:Indoles; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D011725:Pyridines; D012602:Scopolamine Derivatives; D010830:Physostigmine; C061017:linopirdine; D000109:Acetylcholine; D019832:N-Methylscopolamine