Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion

Rationale: The cholinergic system is considered to be essential for attenti on and the degeneration of the cholinergic system in Alzheimer's disease (A D) correlates with the cognitive decline seen in AD patients. The serotoner gic system also degenerates in AD, but its role in the modulation of cognit ive functions, especially attention, is somewhat unclear. Objectives: The p resent study investigated possible differences between cholinergic muscarin ic and nicotinic receptor mediated mechanisms, the role of serotonin (5-HT) and the interaction between the cholinergic and serotonergic systems in th e modulation of attention and response control. Methods: The influences of cholinergic receptor blockade and 5-HT lesions on the performance of rats i n the five-choice serial reaction time task were assessed. The 5-HT lesions were neurochemically verified. Results: The neurochemical analysis indicat ed that the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced quit e specifically in the hippocampi, parieto-occipital and frontal cortices, a nd in the striatum of both p-chloroamphetamine (pCA) and 5,7-dihydroxytrypt amine (5,7-DHT) lesioned rats. The behavioural results showed that the pCA lesion caused a transient increase in impulsivity whereas the 5,7-DHT lesio n temporarily reduced the motor activity and slightly impaired choice accur acy. Furthermore, the blockade of central muscarinic receptors by scopolami ne (0.075 and 0.150 mg/kg), but not nicotinic receptors by mecamylamine (1. 0 or 3.0 mg/kg), impaired the choice accuracy, whereas the blockade of both muscarinic and nicotinic receptors interfered with motor activity, though possibly via peripheral mechanisms. Interestingly, mecamylamine (3.0 mg/kg) reduced impulsivity, whereas scopolamine slightly increased it. Serotonerg ic lesions did not make the rats more susceptible to the effects of cholino lytics on choice accuracy. Conclusions: 5-HT system is not essential for th e modulation of attention, but it is important in the modulation of respons e control. Central muscarinic receptors are important in the modulation of attention, whereas central nicotinic receptors may be more essential in res ponse control. The results do not support there being an interaction betwee n the serotonergic and the cholinergic systems in the modulation of attenti on.