[Abstract Title]. - Society for Neuroscience

This abstract has been authored by Brookhaven Science Associates, LLC under
Contract No. DE-AC02-98CHI-886 with the U.S. Department of Energy.
Title: Behavioral concomitants of congenital learned helplessness and its reversal by a
monoamine oxidase B inhibitor
Authors: *D. SCHULZ, M. M. MIRRIONE, F. A. HENN;
Med. Dept., Brookhaven Natl. Lab., Upton, NY
Abstract: Wild type Sprague Dawley rats were selectively bred for over 50 generations to yield
two strains which differ in their susceptibility to develop learned helplessness. For further
characterization of the animals, 3-4 months old male congenital learned helpless (cLH, n = 10)
and non-helpless (cNLH, n = 12) rats as well as wild types (WT, n = 8) were subjected to three
days of open field testing. On the first two days, the animals were exposed to an empty arena for
10 min each. On the third day, an object exploration paradigm was carried out. Two days later,
helplessness training consisted of 120 inescapable foot-shocks at 0.4 mA with a variable duration
of 5-15 s. The next day, the animals were tested for helplessness by exposure to 15 escapable
foot-shocks which lasted 60 s unless turned off earlier by one lever press. As expected, cLH rats
turned off the foot-shock on fewer trials and required more time to complete the 15 runs
compared to cNLH and WT rats. cNLH rats, in turn, pressed the lever more often than WT
controls and completed the 15 trials sooner. On the first day of open field testing, cLH were
more active than WT rats as measured by the total distance moved. Moreover, over the first two
trials, cLH rats decreased activity levels more than cNLH and WT rats, indicative of enhanced
habituation learning. In cNLH and WT rats, a smaller decrease in activity levels over trials or a
greater resistance to habituate was correlated with more lever presses in the helplessness
paradigm. In cLH rats, indices of „anxiety‟, including less time spent in the center of the open
field, were correlated with fewer lever presses, in line with the known relationship between
depression and anxiety in humans and other animal models of depression. In a different group of
cLH rats, 14 days of treatment with a high dose of deprenyl hydrochloride (10mg/kg; i.p.), which
may cause inhibition of monoamine oxidase (MAO)-A as well as MAO-B activity, attenuated
the escape deficit in the helplessness test; compared to saline-treated controls (n = 5), deprenyltreated
cLH rats (n = 5) turned off the foot-shock on more trials and required shorter times to
complete the 15 runs. Moreover, administration of deprenyl resulted in significant weight loss in
cLH rats, which were found to be overweight compared to cNLH controls (n = 12 and 8,
respectively) at the age of weaning and onwards. In conclusion, the cLH strain shows
consistency with a „depressive‟ phenotype which may be related to abnormalities in MAO-A
and/or MAO-B functioning.
Disclosures: D. Schulz , None; M.M. Mirrione, None; F.A. Henn, None.
Poster
255. Mood Disorders: Animal Models and Treatment Effects II