The NOR task was based on previously established protocols (Nelson et al., 2010, 2011 (link)). One day before the test day, animals received an acclimatisation session. The rats were placed individually into the arena for 1 h. On the following day, rats underwent a re-acclimatisation of 3 min to the arena. In experiments 1, 2 and 3, different groups of rats were injected with saline, 0.4 or 0.8 mg/kg of SKF81297 (s.c.) and returned to their home cage for 15 min. The rats were then given one 5 min sample phase in which the animals were allowed to explore two identical copies of the sample object. In experiment 3, rats were exposed to 5 min sample phase directly after the re-acclimatisation. The total time spent exploring the two identical objects was recorded. After a delay of 10 min (experiment 1) or 24 h (experiments 2 and 3), in which rats were return to their home cage, each rat was replaced for 3 min in the arena, which now contained a novel object and an identical copy of the object previously seen during the sampling phase. In every experiment, at the sampling phase the object exploration time was scored as the total over the full 5 min exposure to the objects. For the choice sessions, the time spent exploring the familiar and novel object was recorded over a total of 3 min. Because the preference for novel object, objects can decline rapidly, these exploration times were scored in three 1-min blocks.
Comparison between the systemic drug studies (experiments 1–3) provides the temporal resolution to distinguish effects at encoding versus retrieval in the NOR procedure. Since both encoding and retrieval were affected, the experiment 4 infusion study used the experiment 1 timeline (infusion before the sample phase and a 10 min retention interval) which does not distinguish effects on encoding and retrieval. Experiment 4 was run over a 6 day cycle in a within-subjects design to reduce the number of animals subjected to the cannulation procedure. On days 1, 3 and 5 rats were placed individually into the arena for 1 h. On days 2, 4 and 6, rats underwent a re-acclimatisation of 3 min to the arena before receiving one of three bilateral mPFC infusions 10 min before the sampling phase: saline, 0.05 μg (0.025 μg/side), 0.1 μg (0.05 μg/side) of the selective D1 receptor agonist SKF81297. The order of the three infusions was counterbalanced using a Latin square design. During the 5 min sampling period the rats were exposed to two identical objects. After a delay of 10 min in which the rats were returned to their home cage, each rat was tested for 3 min in the arena containing a novel object and an identical copy of the object previously seen during the sampling phase. Again, the time spent exploring the familiar and novel object was recorded. In the course of the three sampling/choice sessions, three different object pairs were used, counterbalanced across the infusions conditions.
Comparison between the systemic drug studies (experiments 1–3) provides the temporal resolution to distinguish effects at encoding versus retrieval in the NOR procedure. Since both encoding and retrieval were affected, the experiment 4 infusion study used the experiment 1 timeline (infusion before the sample phase and a 10 min retention interval) which does not distinguish effects on encoding and retrieval. Experiment 4 was run over a 6 day cycle in a within-subjects design to reduce the number of animals subjected to the cannulation procedure. On days 1, 3 and 5 rats were placed individually into the arena for 1 h. On days 2, 4 and 6, rats underwent a re-acclimatisation of 3 min to the arena before receiving one of three bilateral mPFC infusions 10 min before the sampling phase: saline, 0.05 μg (0.025 μg/side), 0.1 μg (0.05 μg/side) of the selective D1 receptor agonist SKF81297. The order of the three infusions was counterbalanced using a Latin square design. During the 5 min sampling period the rats were exposed to two identical objects. After a delay of 10 min in which the rats were returned to their home cage, each rat was tested for 3 min in the arena containing a novel object and an identical copy of the object previously seen during the sampling phase. Again, the time spent exploring the familiar and novel object was recorded. In the course of the three sampling/choice sessions, three different object pairs were used, counterbalanced across the infusions conditions.
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