Archival ReportRestoring Mood Balance in Depression: Ketamine Reverses Deficit in Dopamine-Dependent Synaptic Plasticity
Section snippets
Animals
Adult male Wistar-Kyoto rats (300–350 g; Charles River Laboratories, Wilmington, Massachusetts) were used for their susceptibility to LH (15). Rats were housed singly on a reversed 12-hour dark/light cycle (lights on: 7:00 p.m.) with food and water ad libitum. All experiments were performed in accordance with the guidelines outlined in the National Institutes of Health Guide for Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee of the University
Repeated Injections of Ketamine Restore Escape Behavior in Helpless Rats
Rats received inescapable shocks on day 1 and were tested for escape behavior on 3 consecutive days before electrophysiological recordings (Figure 1A, B). As previously reported (17, 27), inescapable shocks induce helpless behavior in ≈ 50% of the rats (nonhelpless rats: 87 of 172 rats or 50.6%; helpless rats: 85 of 172 rats or 49.4%). Between no-shock (n = 28) and nonhelpless rats (n = 40), there was no difference in the number of failures to escape (F1,27 = .645, p = .429) as well as the
Discussion
In this study, we examined the effect of repeated and acute ketamine injections in a behavioral model of depression. We find that ketamine reverses helpless behavior, restores normal DA neuron population activity, and restores LTP in the vSub-NAc pathway. Our findings indicate that a normal LTP in the NAc shell correlates with a failure to induce helplessness. Moreover, this study shows that the effect of ketamine on synaptic plasticity is, at least in part, due to activation of D1 receptors in
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