[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 291.8/RR83
Topic: F.02.j. Learning and memory: Pharmacology
Support: National Institute of Mental Health grant # MH 64494.
Title: Blockade of alpha4beta2 nicotinic innervation of the mediodorsal thalamic nucleus
improves working memory in rats
Authors: R. D. CANNADY, R. WEIR, B. WEE, E. GOTSCHLICH, N. KOLIA, *E. D.
LEVIN;
Neurobehav Res. Lab. Box 3412, Duke Univ. Med. Ctr., Durham, NC
Abstract: Abnormalities of nicotinic acetylcholine receptors have been linked with cognitive
deficits seen in disorders such as schizophrenia and Alzheimer‟s disease. Nicotinic receptors are
widely distributed in the brain. The differential roles of nicotinic receptors in different brain
areas are still being determined. Nicotinic receptors in the hippocampus and the frontal cortex
have been shown to play key roles in memory. Nicotinic receptors are present in high
concentrations in the thalamus. The thalamic nucleus most closely connected to the frontal cortex
is the mediodorsal (MD) thalamic nucleus. The involvement of MD nicotinic receptors with
working memory was investigated in female Sprague-Dawley rats. We evaluated interactions
between locally infused nicotinic antagonists, and systemic nicotine and the antipsychotic drug
clozapine. The 16-arm radial maze was used to test working memory. After training on the maze
for 18 sessions cannulae were implanted into the MD to locally deliver chronic doses of the
alpha4beta2 nicotinic receptor antagonist DH-beta-E (100 ug/side/day), the alpha7 antagonist
MLA (83 ug/side/day) or vehicle. The rats also received systemic nicotine (5 mg/kg/day) or
saline, delivered sc via minipumps and acute injections of clozapine (0, 1.25, or 2.5 mg/kg, sc).
Blockade of alpha4beta2 nicotinic receptors significantly improved working memory. Treatment
with nicotine reversed this cognitive enhancement. MLA was not seen to significantly affect
working memory. Clozapine did not have an effect on working memory, however there was a
dose dependent effect on response latency. The effect of alpha4beta2 blockade in the MD
thalamic nucleus was opposite of that previously seen in the hippocampus. The differential roles
of nicotinic receptors in different brain areas may explain the complex effects of systemic
nicotinic drug effects on memory.
Disclosures: R.D. Cannady, None; R. Weir, None; B. Wee, None; E. Gotschlich, None; N.
Kolia, None; E.D. Levin , None.
Poster
291. Animal Cognition and Behavior: Learning and Memory: Pharmacology II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm