Task demands dissociate the effects of muscarinic M-1 receptor blockade and protein kinase C inhibition on attentional performance in rats

The cholinergic system is known to be necessary for normal attentional processing. However, the receptors and mechanisms mediating the effects of acetylcholine on attention remain unclear. Previous work in our laboratory suggested that cholinergic muscarinic receptors are critical for maintaining performance in an attention-demanding task in rats. We examined the role of the muscarinic M-1 receptor and protein kinase C (PKC), which is activated by the M-1 receptor, in attention task performance. Rats were trained in an attention-demanding task requiring discrimination of brief (500, 100, 25 ms) visual signals from trials with no signal presentation. The effects of muscarinic M-1 receptor blockade were assessed by administering dicyclomine (0-5.0 mg/kg). The effects of PKC inhibition were assessed by administering chelerythrine chloride (0-2.0 mg/kg). Dicyclomine decreased the accuracy of detecting longer signals in this attention task, including when attentional demands were increased by flashing a houselight throughout the session. Chelerythrine chloride decreased the accuracy of signal detection in the standard version of the task but not when the houselight was flashed throughout the session. The present findings indicate that muscarinic M-1 receptors are critical for maintaining performance when attentional demands are increased, and that PKC activity may contribute to some aspects of attentional performance