Fig. 1.

General experimental design used to determine the effects of systemic administration of KYN, in the presence or absence of the KAT II inhibitor PF-04859989 (PF), on nicotine-evoked glutamate release. Amperometric recordings of glutamatergic activity were initiated after implantation of glutamate-sensitive microelectrodes in the mPFC. Experiments began after 60 min of baseline recording. Nicotine (4 nmol) was pressure-ejected into the recording area and evoked glutamatergic transients were measured. Recordings at t = 0 were treated as baselines. In Experiment 1, (saline/saline group; n = 6), saline was administered 15 min and 45 min after the baseline nicotine pressure ejection. To assess the effects of KYN on nicotine-evoked glutamatergic transients, Experiment 2 (saline/KYN group; n = 6) received systemic administration of saline at 15 min and KYN at 45 min after baseline nicotine ejection. To determine whether the systemic KAT II inhibitor PF is effective in reversing the effects of KYN on nicotine-evoked glutamate release, PF was systemically administered 30 min before (Experiment 3) or after (Experiment 4) KYN (n = 5 each). In all 4 experiments, a series of four nicotine ejections followed 15 min (T₆₀), 45 min (T₉₀), 105 min (T₁₅₀), and 225 min (T₂₇₀) after the second systemic administration of saline/drug. To determine the integrity of glutamatergic terminals and the viability of the sensor following multiple pressure ejections over 270 min, KCl (70 mM) was pressure ejected 15 min (T₂₈₅) after the last nicotine infusion in all the animals and compared with the effects of KCl given at t = 0 (Experiment 6). Experiment 5 tested the effects of PF alone on nicotine-evoked glutamatergic transients.