Cholinergic improvement of a naturally-occurring memory deficit in the young rat

• Published in: Brain research 1996-01, Vol.707 (1), p.13-21
• Main Authors: Smith, Richard D., Kistler, Michael K., Cohen-Williams, Mary, Coffin, Vicki L.
• Format: Article
• Language: English
• Subjects: Acetylcholine; Alzheimer's disease; Animals; Animals, Newborn; Arecoline; Atropine; Avoidance Learning - drug effects; Behavioral psychophysiology; Biological and medical sciences; Cholinergic Agents - pharmacology; Consolidation; Development; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Male; Memory; Memory - drug effects; Neurotransmission and behavior; Nicotine - pharmacology; Oxotremorine - pharmacology; Passive-avoidance response; Pilocarpine; Pilocarpine - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Scopolamine; Tacrine - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)01207-9

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 μg/kg−10 mig/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.