Acute effects of ketamine in the holeboard, the elevated-plus maze, and the social interaction test in Wistar rats

Abstract

Although noncompetitive NMDA receptor antagonists have shown an anxiolyticlike profile in several studies, such effects have not been observed consistently. Previous studies with ketamine, a noncompetitive NMDA antagonist, have employed only shock tests of anxiety based on conflict procedures. In the present experiment, the effect of an acute low dose of ketamine (7 mg/kg) was examined in adult male Wistar rats tested in three nonconflict tests: holeboard, social interaction, and elevated plus‐maze paradigms. The results showed that ketamine decreased time spent in active social interaction and the number of rearings and central activity in the social interaction test. It also decreased the number of entries into and the percentage of time spent in open arms and the total number of entries in the elevated plus‐maze. No significant effect was observed in head dipping in the holeboard test, although the number of crossings did increase. These results suggest an anxiogeniclike effect of ketamine in contrast with results previously described for noncompetitive NMDA receptor antagonists. These effects of ketamine are more similar to those described for stimulant drugs such as caffeine, cocaine, or amphetamine in anxiety tests. Depression and Anxiety 5:29–33, 1997. © 1997 Wiley‐Liss, Inc.

Chronic ketamine use increases serum levels of brain-derived neurotrophic factor

“…Clinical studies have shown that acute administration of ketamine (as well as other NMDA antagonists) ameliorates depressive symptoms in major depressed patients (Zarate et al 2006;Berman et al 2000). In line with these findings, ketamine induces anxiolytic-and antidepressant-like effects in rodent models of anxiety and depression (Kos et al 2006;Yilmaz et al 2002;Silvestre et al 1997), an effect also associated with an increase in BDNF in the hippocampus (Garcia et al 2008). Thus, it is possible that the described antidepressant action of ketamine in humans can be mediated by BDNF.…”

Social interaction and social withdrawal in rodents as readouts for investigating the negative symptoms of schizophrenia

“…For instance, acute and subchronic treatment of MK-801 (0.1–0.3 mg/kg) has been shown to reduce social interaction in adult male rats and mice (de Moura Linck et al, 2008; Matsuoka et al, 2008; Rung et al, 2005). Further, acute and subchronic administration of ketamine (7–30 mg/kg) impaired social interaction in adult male rats (Becker et al, 2003; Silvestre et al, 1997; Uribe et al, 2013). The deficits in social interaction observed in rodents following PCP and other NMDA receptor antagonists seem to correlate to the PCP- and ketamine-induced social withdrawal seen in humans, further supporting social interaction as readout for investigating negative symptoms associated with schizophrenia, more specifically asociality (Sams-Dodd, 1995b).…”

Current pharmacological models of social withdrawal in rats

“…Studies by Silvestre et al (1997) and Koros et al (2007), using acute (7 mg/kg) and subchronic (2-16 mg/kg for 3 days) administration regimens, respectively, reported that ketamine treatment produced a significant decrease in social interaction time in pairs of rats. In contrast other studies have found that subchronic treatment (30 mg/kg for 5 days) had no effect on social interaction time, but significantly reduced nonaggressive behaviour (e.g.…”