Figure 5.

Metabotropic glutamate receptor 5 (mGluR5) antagonism rescues long-term memory and decreases synaptic p-ERK1/2 content in BTBR mice. (a) Left, schematic illustration of the handling and injection schedule for BTBR mice treated with 10% cyclodextrin (vehicle) or the ampakine CX929 (5 mg/kg). Starting on the morning of the second day of handling, animals received twice daily injections of vehicle for 4 days (indicated by ‘—‘). Starting on the morning of the second day of habituation, animals received twice daily injections of either vehicle or CX929 (indicated by ‘x'). The final injection occurred on the afternoon of the last day of habituation (no injections given on days of training (T) or retention (R) trials). Right, Ampakine- and vehicle-treated BTBR mice showed no significant differences in long-term memory, as measured by OLM retention trial discrimination index (P=0.33; N⩾7/group). (b) Left, treatment regimen associated with administration of the mGluR5 antagonist, MPEP, to B6 and BTBR mice. Following 4 days of once daily sterile 0.9% saline injections (indicated by ‘—‘), which were started on the morning of the second day of habituation, MPEP (5 mg/kg) or vehicle was administered 30 min before a 5-min OLM training (T) trial (indicated by ‘x'). Right, as measured by retention trial discrimination index, vehicle-treated BTBRs performed significantly worse than vehicle-treated B6s; in contrast, MPEP-treated BTBRs performed at levels of B6 mice (Holm-Sidak post hoc analysis, *P<0.05, **P<0.01; N⩾11/group). (c) Immunolabeling intensity frequency distribution for p-ERK1/2+ elements double labeled for PSD95 in vehicle- and MPEP-treated BTBR mice. Note the slight leftward shift in MPEP-treated mice (group mean±SEM values shown; N⩾11/group). (d) Bar graph shows that the numbers of p-ERK1/2+ PSDs are lower in vehicle-treated BTBR as compared with vehicle-treated B6 mice (*P<0.05), and these group B6 are not affected by MPEP treatment (N⩾11/group; values expressed as a percent of the B6 vehicle group mean).