Blockade of muscarinic, rather than nicotinic, receptors impairs attention, but does not interact with serotonin depletion.
BACKGROUND
The cholinergic system is considered to be essential for attention and the degeneration of the cholinergic system in Alzheimer's disease (AD) correlates with the cognitive decline seen in AD patients. The serotonergic system also degenerates in AD, but its role in the modulation of cognitive functions, especially attention, is somewhat unclear.


OBJECTIVE
The present study investigated possible differences between cholinergic muscarinic and nicotinic receptor mediated mechanisms, the role of serotonin (5-HT) and the interaction between the cholinergic and serotonergic systems in the modulation of attention and response control.


METHODS
The influences of cholinergic receptor blockade and 5-HT lesions on the performance of rats in the five-choice serial reaction time task were assessed. The 5-HT lesions were neurochemically verified.


RESULTS
The neurochemical analysis indicated that the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced quite specifically in the hippocampi, parieto-occipital and frontal cortices, and in the striatum of both p-chloroamphetamine (pCA) and 5, 7-dihydroxytryptamine (5,7-DHT) lesioned rats. The behavioural results showed that the pCA lesion caused a transient increase in impulsivity whereas the 5,7-DHT lesion temporarily reduced the motor activity and slightly impaired choice accuracy. Furthermore, the blockade of central muscarinic receptors by scopolamine (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. Serotonergic lesions did not make the rats more susceptible to the effects of cholinolytics on choice accuracy.


CONCLUSIONS
5-HT system is not essential for the modulation of attention, but it is important in the modulation of response control. Central muscarinic receptors are important in the modulation of attention, whereas central nicotinic receptors may be more essential in response control. The results do not support there being an interaction between the serotonergic and the cholinergic systems in the modulation of attention.
Ruotsalainen
S
S
A. I. Virtanen Institute, University of Kuopio, Kuopio, Finland.
Miettinen
R
R
MacDonald
E
E
Koivisto
E
E
Sirviö
J
J
D015116:5,7-Dihydroxytryptamine / Q000008:administration & dosage; D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000008:administration & dosage; D013647:Task Performance and Analysis; D010133:p-Chloroamphetamine / Q000494:pharmacology
D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D010133:p-Chloroamphetamine