Blockade of muscarinic acetylcholine receptors in the ventral tegmental area prevents acquisition of food-rewarded operant responding in rats

Abstract

We recently found that muscarinic receptor (mAChR) stimulation in the ventral tegmental area (VTA) is involved in the acquisition of a feeding task. To investigate the involvement of VTA mAChR and nicotinic receptors (nAChR) in the acquisition and performance of a food-rewarded lever-pressing task. In experiment 1 (N=54), rats were trained under a fixed ratio 1 schedule of reinforcement and received bilateral intra-VTA microinjections of scopolamine (0, 2.5 or 5 microg/0.5 microl) or mecamylamine (0, 5 or 10 microg/0.5 microl) before each of the first four sessions. Before session 10, all rats that initially received a dose of either compound now received the vehicle and vice versa. In experiment 2 (N=14), rats were tested with scopolamine or mecamylamine while lever pressing under a progressive ratio schedule of reinforcement. In experiment 1, lever pressing by rats initially treated with any mecamylamine dose or the scopolamine vehicle rose to and stayed at maximal levels for the remaining sessions. Responding by rats initially treated with the 2.5- or 5-microg dose of scopolamine remained low, even after the cessation of scopolamine treatment, and gradually rose to maximal levels by the final sessions. Injections of scopolamine 1 to 2 mm dorsal to the VTA had no significant effect on responding. In experiment 2, neither of the compounds significantly affected break points. Stimulation of VTA mAChR, but not of nAChR, is necessary for the acquisition of a food-rewarded lever-pressing task and neither is necessary for the performance of the task.