I. Antidepressants and sexual behavior: Weekly ketamine injections increase sexual behavior initially in female and male rats

The present study characterized the effects of weekly ketamine injections on sexual behavior and anxiety in female and male rats, using a dosing protocol that mimics human therapeutic treatment for depression. In Experiment 1A, ketamine (10 mg/kg, i.p.) or saline was injected once per week for four consecutive weeks. The partner preference paradigm was used to measure sexual motivation 30 min after each weekly injection. Briefly, subjects were first given a 10-min test during which they could choose to spend time in the vicinity of a sexually receptive female stimulus or a sexually experienced male stimulus, however physical contact was restricted (no-contact). Immediately after, subjects were given unrestricted access to the stimulus animals (contact). After a washout period, subjects received four additional weekly injections of ketamine or saline, and then were tested for anxiety-like behavior on the elevated plus maze (EPM) after the last injection (Experiment 1B). For Experiment 2, similar procedures were used to test the effects of weekly ketamine injections on sexual motivation (Experiment 2A) and anxiety (Experiment 2B) in male subjects. In female subjects, ketamine increased sexual motivation as measured by greater time spent with the male stimulus, decreased likelihood of leaving after receiving mounts, and shorter return latencies after receiving intromissions, when compared to saline controls. In male subjects, ketamine shortened latency to first mount and first intromission, as well as increased time spent with the female stimulus. Very little anxiety was observed in either group (ketamine or saline) of female or male subjects when tested on the EPM. In conclusion, even after four weeks of ketamine exposure, sexual dysfunction did not emerge in either females or males. In contrast, ketamine increased sexual motivation in both females and males, with an initial robust response. However, as both groups gained sexual experience, the impact of ketamine diminished.