Although recent investigations of major depressive disorder (MDD) have focused on the monoaminergic system, accumulating evidence suggests that alternative pathophysiological models of MDD and treatment options for patients with MDD are needed. Animals subjected to chronic forced swim stress (CFSS) develop behavioral despair. The purpose of this study was to investigate the in vivo effects of CFSS in the rat prefrontal cortex (PFC) with 7 T and short-echo-time proton magnetic resonance spectroscopy (1H MRS). Ten male Wistar rats underwent 14 days of CFSS, and in vivo1H MRS and forced swim tests were performed before and after CFSS. Point-resolved spectroscopy was used to quantify metabolite levels in the rat PFC. The spectral analyses showed that in vivo1H MRS can be used to reliably assess the Glu system. The rats showed significantly increased immobility times and decreased climbing times in the FST after CFSS, which suggested that the rats developed behavioral despair. The pre-CFSS and post-CFSS Glu and Gln levels did not significantly differ (P > 0.050). The levels of myo-inositol, total choline, and N-acetylaspartate, myo-inositol/creatine, and total choline/creatine increased significantly (P < 0.050). Similar findings have been reported in patients with MDD. Taken together, these results suggested that the CFSS-induced metabolic alterations were similar to those found in patients and that high-field and short-echo-time in vivo1H MRS can be used to investigate depression-induced metabolic alterations. Such investigations might provide alternative insights into the nonmonoaminergic pathophysiology and treatment of depression.