Task demands dissociate the effects of muscarinic M1 receptor blockade and protein kinase C inhibition on attentional performance in rats

Abstract

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.

Figure 1

The figure depicts relative hits (A), relative correct rejections (B) and omissions per session (C) following each dicyclomine dose (0–5.0 mg/kg). In Figure 1A, the bars denote the different signal durations (500, 100 and 25 ms). Dicyclomine produced a significant dose X signal duration that did not further interact with task (p < .05; n = 9). Thus, the data shown here are combined from the standard and flashing houselight conditions. Compared to vehicle, dicyclomine (0.625, 2.5 and 5.0 mg/kg) decreased the accuracy of detecting the 500-ms signal and at one dose (2.5 mg/kg) decreased the accuracy of detecting the 100-ms signal. The asterisks denote dicyclomine doses that were significantly different compared with vehicle administration (p < .05). There were no effects of dicyclomine on correct rejections or omissions.

Figure 2

The figure depicts relative hits (A), relative correct rejections (B) and omissions per session (C) following each chelerythrine chloride dose (0–2.0 mg/kg) in the standard task trained prior to drug administration. In Figure 2A, the bars depict the different signal durations (500, 100 and 25 ms). The asterisk denotes a significant decrease in the relative hits following 2.0 mg/kg chelerythrine chloride compared with vehicle administration (p < .05; n =7). There were no significant effects of chelerythrine chloride on correct rejections or omissions.

Figure 3

The figure depicts relative hits (A), relative correct rejections (B) and omissions per session (C) following each chelerythrine chloride dose (0-2.0 mg/kg) in the distracter task with the houselight flashing throughout the session. In Figure 3A, the bars denote the different signal durations (500, 100 and 25 ms). Chelerythrine chloride did not differentially affect hits, correct rejections or omissions during the distracter condition (n = 7).