Postnatal homocysteine administration induces anxiety-like behavior in rats: protective effects of folic acid

Anxiety is a prevalent neuropsychiatric disorder caused by excitation or destruction of various areas of the brain, including the hippocampus. Homocysteine (Hcy) has recently been identified as a potentially excitatory amino acid and a risk factor for central nervous system disorders. Therefore, this study was designed to investigate the effects of homocysteine administration on anxiety-like behavior in rats. Also, we aimed to investigate the possible protective role of folic acid administration as a potent antioxidant on alterations elicited by hyperhomocysteinemia in the hippocampus.

The rat pups were divided randomly into four groups. Group I received normal saline, group II received Hcy subcutaneously twice a day at 8-h intervals (0.3- 0.6 µmol/g body weight), group III received Hcy + folic acid (0.011 µmol/g body weight) and group IV received folic acid on postnatal day (PD) 4 until 25. On the 26th day, anxiety and exploratory behavior of animals was examined using the open field and elevated plus maze tests, respectively. Also, histological study was performed.

Hcy administration increased the plasma total Hcy level. Folic acid significantly reduced plasma Hcy level. Hcy induced anxiety-like behavior. The number of rearing significantly reduced following Hcy administration (p < 0.05). The percentage of time spent in the open arms of the elevated plus maze significantly reduced and percentage of time spent in the closed arms increased following Hcy exposure in the rats (p < 0.001) as the control group. Folic acid treatment significantly elevated the percentage of time spent in the open arms and reduced the percentage of time spent in the closed arms in Hcy + Folic acid exposure rats as Hcy rats (p < 0.05). Histological study indicated that there was no significant change in number of hippocampal cells among groups.

Hcy can induce anxiety-like behavior and folic acid has protective effect against Hcy- induced anxiety.