Learning enhancement with neuropeptides.
OBJECTIVE
Previous work has demonstrated that two synthetic peptides can prevent prenatal alcohol-induced damage as assessed by prevention of learning abnormalities in adult offspring as well as improve outcome from traumatic brain damage. The current studies were undertaken to evaluate whether these peptides could enhance performance in a learning and memory paradigm when administered either prenatally or to aged mice.


METHODS
For prenatal treatment, C57Bl6/J mice were treated on gestational day 8 with 1 oral administration of D-NAP or D-SAL alone or D-NAP+D-SAL or a double dose of D-SAL. Control groups were same-regimen treated with vehicle alone. Learning was assessed in adult male offspring (35-50 days) by using the Morris water maze. To evaluate aged animals, 12-month-old mice were treated with D-NAP and D-SAL or vehicle alone daily and tested on the Morris water maze.


RESULTS
Offspring exposed prenatally to D-NAP+D-SAL learned significantly faster than controls, with an earlier onset of learning and an overall decreased latency to find the hidden platform (P < .05). Animals exposed prenatally to either D-NAP or D-SAL alone learned similar to control, with a trend toward faster latencies. Aged animals who received D-NAP+D-SAL learned significantly faster than age-matched controls, with an earlier onset of learning (P < .05).


CONCLUSIONS
Combined D-NAP+D-SAL enhanced learning in healthy young mice and aged mice. These findings suggest potential therapeutic interventions not only during a critical developmental period, but also in aged animals.
Toso
Laura
L
Unit on Perinatal and Developmental Neurobiology, National Institute of Child Health and Development, National Institutes of Health, Bethesda, MD, USA.
Endres
Melanie
M
Vink
Joy
J
Abebe
Daniel T
DT
Brenneman
Douglas E
DE
Spong
Catherine Y
CY
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology* / Q000502:physiology; D011247:Pregnancy
D009479:Neuropeptides; D009842:Oligopeptides; C502410:seryl-alanyl-leucy-leucyl-arginyl-seryl-isoleucyl-prolyl-alanine; C425904:davunetide