Cholinergic improvement of a naturally-occurring memory deficit in the young rat.
In a single-trial, passive-avoidance response (PAR) paradigm, young rats at post-natal day (PND) 16 were found to exhibit a performance deficit that diminished progressively with age. When administered prior to training, single peripheral injections of cholinomimetic drugs, either a muscarinic agonist (arecoline, pilocarpine or oxotremorine), an acetylcholinesterase inhibitor (tacrine or E2020), or nicotine, increased the response latencies for young rats to that of adult levels in a dose-dependent manner (overall dose range = 0.003 microgram/kg-10 mg/kg). Neither the cholinergic antagonists scopolamine, atropine or mecamylamine, nor a series of non-cholinergic drugs, diazepam, haloperidol, phenobarbital, pargyline, D-amphetamine, imipramine, piracetam or N-methyl-D-aspartate (NMDA) increased PAR latencies. When 0.1 mg/kg scopolamine was given to young rats prior to arecoline, the dose-effect curve for enhanced latency times was shifted to the right. Higher doses of scopolamine completely blocked the effects of arecoline. Scopolamine (0.001-1.0 mg/kg) administered subsequent to, rather than before PAR training, blocked the usual arecoline-induced enhancement of response latencies. Alternatively, consolidation could be facilitated with different doses of tacrine (0.0003-10 mg/kg). These results demonstrate that young rats fail to remember the PAR but that retention for this task can be specifically enhanced with cholinomimetic drugs.
Smith
R D
RD
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Kistler
M K
MK
Cohen-Williams
M
M
Coffin
V L
VL
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000187:drug effects*; D018678:Cholinergic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013619:Tacrine / Q000494:pharmacology
D018678:Cholinergic Agents; D010862:Pilocarpine; D013619:Tacrine; D010095:Oxotremorine; D009538:Nicotine