*D. S. GOLDWATER1, R. G. HUNTER3, C. PAVLIDES3, B. S. MCEWEN3, J. H. MORRISON2;
2Dept. of Neurosci., 1Mount Sinai Scf Med., New York, NY; 3Lab. of Neuroendocrinology, Rockefeller Univ., New York, NY

Chronic stress is a known risk factor for depressive disorders, which may involve dysfunction of the prefrontal cortex (PFC) as well as alterations to the dopaminergic (DA) system. In animal models, chronic stress leads to behavioral alterations that parallel those seen in human depressive disorders, yet the underlying neuronal changes leading to such behaviors are poorly understood. Previous data have shown that pyramidal cells in the rodent medial PFC (mPFC) undergo dendritic shrinkage following long-term restraint stress that is reversible with a rest period . The goals of this project were to determine 1) if chronic restraint stress impacts mPFC function with respect to synaptic plasticity, 2) if PFC stress-related functional alterations are DA-dependent, and 3) if these stress-related functional consequences are reversible. Specifically, we investigated whether stress affects the ability of intra-mPFC connections to induce and maintain long-term potentiation (LTP) as well as the known ability of DA to modulate LTP via D1 receptor activation. Three groups of male Sprague-Dawley rats were used: stress (S), rest (R), and control (C). The S group was subjected to 21 days of chronic restraint stress for six hours per day while the R group received an identical stress followed by 21 stress-free days in their home cages. LTP experiments were performed on mPFC slices by stimulating infralimbic (IL) area layer II and recording from layer V. The dopamine (D1) receptor agonist, SKF 38393 (Sigma, 0.3 mm), was infused into the bath at a constant rate. We found that while LTP per se was unaffected by stress, the ability of D1 receptor activation to modulate synaptic potentiation was significantly inhibited in S as compared to C, while the R group demonstrated complete DA-response recovery. These data show that previously demonstrated morphologic recovery from stress is accompanied by restoration of DA-mediated modulation of LTP, implying that effects of stress on synaptic function in these neurons is also reversible. Studies with a separate set of S, R, and C, animals are currently underway using both D1 ligand-binding autoradiography and D1 GTPgS autoradiography to determine stress effects on D1 receptor availability and functional coupling, respectively.

Support Contributed By: NIH Grant MH58911

Program No. 628.4/XX7
Poster presentation:Tuesday, Nov 06, 2007, 11:00 AM -12:00 PM
Location: San Diego Convention Center: Halls B-H