Proefschrift_Holstein

Reward modulation of cognitive function: the nucleus accumbens

rewarded task-switching performance. Stereotaxic surgery was performed under isoflurane anaesthesia. Animals were placed on a stereotaxic apparatus (David Kopf Instruments) and received subcutaneously injections with 0.1 ml of bupivicaine at the incision site. An incision was made to expose the skull and the incisor bar was adjusted to align bregma and lambda in the same horizontal plane. Excitotoxic lesions were made by infusing 0.4 µl of N-methyl-D-aspertate (NMDA: 10mg/ml in saline) over 4 minutes into the AcbC [anteroposterior +1.6, mediolateral +/- 2.2, dorsoventral -7.5 mm relative from bregma, according to the rat brain atlas (Paxinos and Watson, 2007)]. The needle was left in place for 2 minutes to allow for diffusion before being retracted. Animals in the sham group underwent the exact same procedure, except that only saline was infused. At the end of surgery, animals received a subcutaneous injection of 0.1 ml Rimadyl and 0.2 ml intraperitoneal injection of procaine penicillin solution (300mg/kg). Rats were given at least 6 (max. 10) days to recover and were subjected to 4 days of food deprivation before the start of 5 days of additional discrimination training and two test days. Histology Rats were deeply anaesthetized with sodium pentobarbital and transcardially perfused with 400 ml of 4% paraformaldehyde in 0.1 M sodium phosphate buffer. Brains were postfixed for 1 hour in 4% paraformaldehyde, rinsed in phosphate buffered saline (PBS) for 30 minutes before being placed in 30% sucrose solution in PBS overnight. The brains were frozen and 40 µm sections were collected on a cryostat. Every third section was collected on a slide and stained with cresyl violet. Slides were examined for placement and extent of the lesion by microscopically examining the sections. Statistical tests Discrimination training data are presented as the average number of correct and incorrect lever presses per minute (recorded during the first 10s of each trial) on the auditory and visual discrimination sessions separately, and collapsed across the two stimuli. We present performance on test in terms of accuracy (correct minus incorrect lever presses, again as an average per minute recorded during the first 10s of each trial). We assessed the effect of reward on task-switching performance with a repeated-measures GLM with the factors reward (high vs. low), switching (switch vs. repeat) and accuracy (correct vs. incorrect) and anticipated that reward would improve task-switching performance. To increase the number of trials on the post-surgery test (where the group sizes are smaller, i.e. 12 instead of 24 during pre-surgery testing), all animals received two tests (post1 and post2) in each reward condition in an ABBA design. We first assessed whether there were any effects of session (post1 vs. post2) on rewarded task-switching performance or overall accuracy. In the absence of an interaction, we collapsed data across post-tests.

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