[Abstract Title]. - Society for Neuroscience

Authors: *B. N. SRIKUMAR, V. PRIYA, V. BHAGYA, J. VEENA, T. R. RAJU, B. S.
SHANKARANARAYANA RAO;
Dept Neurophysiol, Natl. Inst. Mental Hlth. Neu Sci., Bangalore, India
Abstract: Severe, traumatic stress or repeated exposure to stress can result in long-term
deleterious effects on the hippocampus, including dendritic atrophy and cell death, which, in
turn, result in memory impairments and precipitate neuropsychiatric disorders like depression
and anxiety. Further, chronic stress is known to affect hippocampal long-term potentiation
(LTP), a synaptic model of memory. In an earlier study, we reported that the cholinergic
muscarinic agonist, oxotremorine reverses chronic restraint stress-induced impairment in the
performance of the radial arm maze task [Srikumar et al (2006) Neuroscience 143:679-688].
However, the cellular mechanisms recruited by oxotremorine to produce its effects are not
known. Accordingly, in the present study, we assessed the effects of oxotremorine treatment on
LTP in the Schaffer collateral-CA1 synapses and spatial learning and memory in the Morris
water maze. Male Wistar rats were subjected to restraint stress for 21 days (6h/day) and
oxotremorine treatment (0.1 and 0.2 mg/kg, i.p, once daily) for 10 days followed by behavioral
evaluation in the water maze. In LTP experiments, rats underwent 10 daily injections of
oxotremorine (0.2 mg/kg, i.p) after 21 days of restraint stress. Following 20 minutes of baseline
recording of extracellular field potentials at the Schaffer collateral-CA1 synapses, LTP was
induced by the high frequency stimulation (HFS) protocol. Stressed rats showed impairment in
hippocampal CA1-LTP and the acquisition of the water maze task. Oxotremorine treatment
significantly reversed the stress-induced impairment of the hippocampal CA1-LTP and learning
deficits. These results together with our earlier findings demonstrate the cholinergic system as a
good target in the development of drugs for the treatment of stress and stress-related disorders.
Disclosures: B.N. Srikumar , None; V. Priya, None; V. Bhagya, None; J. Veena, None; T.R.
Raju, None; B.S. Shankaranarayana Rao, None.
Poster
282. Stress and the Brain: Cellular Actions of Stress
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 282.15/OO22
Topic: E.06.d. Cellular actions of stress
Support: NIH Grants NS28912, MH73136
NARSAD young investigator award
Title: Stress induces dendritic spine loss within hours in adult hippocampus: novel mechanisms