Impaired short-term memory resulting from postnatal undernutrition is attenuated by physostigmine

Early-life undernutrition impairs the short-term memory capacity of adult rats (90 days of age) trained on a conditional—spatial discrimination task (Castro, Tracy, & Rudy, Behavioral Brain Research, 32, 255–264, 1989). While well-nourished control animals perform above 90% correct when the interval separating the forced run and choice run is 180 s, the performance of the undernourished animals falls to chance (50%) when the delay interval is increased to 90 s. We now report that this performance decrement can be attenuated by the administration of the anticholinesterase, physostigmine. However, the effects of physostigmine were dose dependent. While 0.02 mg/kg of physostigmine improved the performance of the undernourished animals so that they performed significantly above chance at the 180-s delay interval, neither 0.2 nor 0.002 mg/kg of physostigmine improved performance. We concluded that this effect was centrally mediated since scopolamine hydrobromide (1.0 mg/kg) which blocks both central and peripheral cholinergic receptors blocked physostigmine's performance-improving effect, while methyl-scopolamine (1.0 mg/kg) which blocks only peripheral receptors did not. These are the first results which suggest that the short-term memory impairments produced by early-life undernutrition can be attenuated by enhancing central cholinergic functioning.