Three weeks after surgery, behavioral testing on the attentional set-shifting task began. Prior to testing, the DREADDS were activated by clozapine (Gomez et al. 2017 ; Tan et al. 2020 (link)) either by systemic injection (Experiment 1) or intracranial infusion (Experiment 2).
In Experiment 1, clozapine dihydrochloride (Hello Bio) was dissolved in sterile saline. Twenty minutes before the test began, all rats received an intraperitoneal (I.P.) injection of clozapine dihydrochloride at a dose of 4 mg/kg (as salt).
In Experiment 2, clozapine dihydrochloride (Hello Bio) was dissolved in sterile saline at a dose of 1 μg/μL (as salt). Fifteen minutes prior to testing, rats were lightly restrained, the obturators removed, and 33-gauge stainless steel infusion cannulae (Plastic One) that projected 2.0 mm beyond the tip of the guide cannulae were inserted. Each pair of infusion cannula was connected to two 5 μL Hamilton syringes (Bonaduz) mounted on 2 infusions pumps (Harvard Apparatus Ltd). A volume of 0.25 μL per hemisphere was infused over 1 min. The infusion cannulae were left in situ for a further 1 min to allow absorption of the bolus. The infusion cannulae were then removed and the obturators replaced.
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