Repetitive Self-Grooming Behavior in the BTBR Mouse Model of Autism is Blocked by the mGluR5 Antagonist MPEP methods
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MATERIALS AND METHODS
Inbred strains C57BL/6J (B6) and BTBR T+ tf/J (BTBR) were purchased from The Jackson Laboratory (Bar Harbor, ME) and bred in a conventional mouse vivarium at the National Institute of Mental Health (NIMH), Bethesda, MD, using harem breeding trios. After 2 weeks with a male, females were separated into individual cages before delivery. Pups were kept with the dam until weaning at postnatal day (PND) 21. After weaning, juveniles were housed by sex and strain in standard plastic cages in groups not exceeding four per cage. Cages were housed in ventilated racks in temperature (20 °C) and humidity (∼55%) controlled colony rooms, on a 12-h circadian cycle, lights on from 0700 to 1900 h. Standard rodent chow and tap water were available ad libitum. In addition to standard bedding, a Nestlet square, shredded brown paper and a cardboard tube were provided in each cage....
Sociability
Social approach was tested in an automated three-chambered apparatus using methods described earlier (;;, ). The apparatus was a rectangular, three-chambered box made from clear polycarbonate. Retractable doorways within the two dividing walls allowed access to the side chambers. Number of entries and time spent in the chambers were automatically recorded from photocells embedded in the doorways. A top mounted CCTV camera (Security Cameras Direct, Luling, TX) was placed over the boxes to record the session, for subsequent scoring of the videos for time spent sniffing the novel mouse and novel object. The apparatus was cleaned with 70% ethanol and water between subjects with at least 5 min between cleaning and the start of the next test session to allow for ethanol evaporation and clearance of ethanol vapor odors. Mice used as the novel stimulus target were 129Sv/ImJ, aged 12&...
RESULTS
illustrates the open field exploratory locomotion for both B6 and BTBR after an acute injection of the two highest doses of the MPEP doses that were tested in the self-grooming assay. The time course for total distance traversed in the novel open field over a 30-min time period was highly significant, as expected, representing habituation to the novel open field by both B6 (panel a; F (5, 20) =66.92, p <0.0001) and BTBR (panel b; F (5, 21) =65.99, p <0.0001). A significant interaction was detected between strain and total distance traversed (F (5, 42) =8.64, p <0.001), reflecting the higher initial open field activity of BTBR, as reported earlier (; ). Of interest is the lack of significant reductions in locomotor activity after MPEP in the strains tested, supporting earlier published literature in rats (; ). In fact, slightly higher total distance scores were dete...
Reductions of Repetitive Self-Grooming Behavior in BTBR Mice Treated with Risperidone, Confounded by Reductions in Op...
illustrates open field locomotion after an acute injection of risperidone. The time course for total distance traversed in the novel open field over a 30-min time period was highly significant, as expected, representing habituation to the novel open field for both B6 (F (5, 40) =9.04, p <0.0001) and BTBR (F (5, 33) =9.55, p <0.0001). A significant effect of drug was detected for B6 (panel a; F (3, 40) =27.20, p <0.05) and BTBR (panel b; F (3, 33) =11.31, p <0.001). The interaction of drug × distance traversed was significant for B6 (F (3, 15) =4.49, p <0.01) and BTBR (F (3, 15) =4.29, p <0.01). Tukey's post hoc comparisons reveal significant reductions in total distance scores after risperidone treatment in B6, at each dose compared with vehicle (0.125 mg/kg, q =8.01, p <0.05; 0.25 mg/kg, q =7.90, p <0.05; 0.5 mg/kg, q =12.15,...
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Inbred strains C57BL/6J (B6) and BTBR T+ tf/J (BTBR) were purchased from The Jackson Laboratory (Bar Harbor, ME) and bred in a conventional mouse vivarium at the National Institute of Mental Health (NIMH), Bethesda, MD, using harem breeding trios. After 2 weeks with a male, females were separated into individual cages before delivery. Pups were kept with the dam until weaning at postnatal day (PND) 21. After weaning, juveniles were housed by sex and strain in standard plastic cages in groups not exceeding four per cage. Cages were housed in ventilated racks in temperature (20 °C) and humidity (∼55%) controlled colony rooms, on a 12-h circadian cycle, lights on from 0700 to 1900 h. Standard rodent chow and tap water were available ad libitum. In addition to standard bedding, a Nestlet square, shredded brown paper and a cardboard tube were provided in each cage. Previous studies in our laboratory documented no sex differences in sociability or self-grooming in BTBR and B6 (; ). Therefore, male and female mice were used in all studies in approximately equal proportions. Experiments were conducted in dedicated behavioral testing rooms during the standard lig...
Social approach was tested in an automated three-chambered apparatus using methods described earlier (;;, ). The apparatus was a rectangular, three-chambered box made from clear polycarbonate. Retractable doorways within the two dividing walls allowed access to the side chambers. Number of entries and time spent in the chambers were automatically recorded from photocells embedded in the doorways. A top mounted CCTV camera (Security Cameras Direct, Luling, TX) was placed over the boxes to record the session, for subsequent scoring of the videos for time spent sniffing the novel mouse and novel object. The apparatus was cleaned with 70% ethanol and water between subjects with at least 5 min between cleaning and the start of the next test session to allow for ethanol evaporation and clearance of ethanol vapor odors. Mice used as the novel stimulus target were 129Sv/ImJ, aged 12-20 weeks old, bred and maintained in the NIMH vivarium from breeding pairs originally obtained from The Jackson Laboratory, and matched to the subject mice by sex. Stimulus mice were habituated to the apparatus and to the wire cup enclosure, several days before the start of experiments, for 30...
illustrates the open field exploratory locomotion for both B6 and BTBR after an acute injection of the two highest doses of the MPEP doses that were tested in the self-grooming assay. The time course for total distance traversed in the novel open field over a 30-min time period was highly significant, as expected, representing habituation to the novel open field by both B6 (panel a; F (5, 20) =66.92, p <0.0001) and BTBR (panel b; F (5, 21) =65.99, p <0.0001). A significant interaction was detected between strain and total distance traversed (F (5, 42) =8.64, p <0.001), reflecting the higher initial open field activity of BTBR, as reported earlier (; ). Of interest is the lack of significant reductions in locomotor activity after MPEP in the strains tested, supporting earlier published literature in rats (; ). In fact, slightly higher total distance scores were detected after MPEP administration to B6 (panel a; F (2, 21) =4.32, p <0.05) at the 30 mg/kg dose of MPEP, using a stringent Tukey's post hoc comparison. Similarly, MPEP administration increased total distance scores in BTBR (panel b; F (2, 21) =6.02, p <0.01). Tukey's post hoc analysi...
illustrates open field locomotion after an acute injection of risperidone. The time course for total distance traversed in the novel open field over a 30-min time period was highly significant, as expected, representing habituation to the novel open field for both B6 (F (5, 40) =9.04, p <0.0001) and BTBR (F (5, 33) =9.55, p <0.0001). A significant effect of drug was detected for B6 (panel a; F (3, 40) =27.20, p <0.05) and BTBR (panel b; F (3, 33) =11.31, p <0.001). The interaction of drug × distance traversed was significant for B6 (F (3, 15) =4.49, p <0.01) and BTBR (F (3, 15) =4.29, p <0.01). Tukey's post hoc comparisons reveal significant reductions in total distance scores after risperidone treatment in B6, at each dose compared with vehicle (0.125 mg/kg, q =8.01, p <0.05; 0.25 mg/kg, q =7.90, p <0.05; 0.5 mg/kg, q =12.15, p <0.05) during the 30-min test session, and at each of the 5-min time bins. Similarly, significant reductions in open field locomotion were detected in BTBR at each dose of risperidone (0.125 mg/kg, q =3.84, p <0.05; 0.25 mg/kg, q =4.69, p <0.05; 0.5 mg/kg, q =8.19, p <0.05). Add...
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