Figure 5.

Ketamine, but not GLYX-13 increases 5-HT₂-induced head twitch and impulsivity. (a,b) Male C57Bl/6 mice were administered vehicle (i.v.), GLYX-13 (3 mg/kg, i.v.) or ketamine (10 mg/kg, i.v.), and 24 h later were administered a single dose of the 5-HT_2A/C receptor agonist DOI (5 mg/kg, i.p.). The numbers of head twitches are shown (a) over the total 30 min test period. n=6 (sal), 6 (ket), 5 (GLYX-13). One-way ANOVA indicated a treatment effect: F_2,14=69.32, p<0.0001, with ketamine producing more head twitches t(10)=10.27, ***p<.0001. The same data are shown in (b) for 5 min blocks. (c–h) show the results of the serial reaction time task (SRTT). Mice were first trained to respond to a 70% correct criterion through increasingly short stimulus durations over the course of ~5 weeks. (c) Final 6 sessions of training (5 s stimulus duration, 5 s ITI). (d) Retraining before GLYX-13 administration. Mice were administered vehicle (i.v.) or ketamine (10 mg/kg, i.v.) and then, after retraining, vehicle or GLYX-13 (3 mg/kg, i.v.) in a crossover design. Results are shown as mean±SEM n=6 (ctrl), 7 (ket); 5 (ctrl), 7 (GLYX-13). Data in e–h were analyzed with two-way repeated measures ANOVA, followed by post hoc t-tests when indicated. Initial measure validation demonstrated that (e) reducing stimulus duration, F_3,33=35.21, p<0.0001 and (f) increasing the intertrial interval (ITI), F_3,33=18.56, p<0.0001 resulted in increased omissions and impulsivity, respectively. A significant treatment × ITI interaction, F_3,33=3.41, p<0.05 supports a ketamine-associated increase in impulsivity at the longest ITI, t(11)=3.47, **p<0.01. For analysis of attention and impulsivity, respectively, mice were then tested with a session that consisted of random presentation of two trial types; those with (g) short stimulus duration (0.5 s) and standard ITI (5 s) in which omissions were measured, or, those with (h) long ITI (10 s) and standard stimulus duration (5 s) in which premature responses were determined. Ketamine treatment was associated with reduced omissions across all trials F_1,11=4.90, *p<0.05 though this was particularly evident on short stimulus duration trials t(11)=2.74, *p<0.05. Analysis of impulsivity demonstrated an interaction, F_1,11=5.02, p<0.05 confirmed by increased premature responses in ketamine treated animals in trials with a long ITI t(11)=2.91, **p<0.01. In contrast GLYX-13 treatment did not affect impulsivity F_1,10=0.46, p>0.05, but was observed to increase attention across trial types F_1,10=5.99, p<0.05, again most evident in trials with a short stimulus duration t(10)=2.45, *p<0.05.