A. Blondel et al., Characterisation of the effects of nicotine in the five-choice serial reaction time task in rats: antagonist studies, PSYCHOPHAR, 149(3), 2000, pp. 293-305
Rationale: Nicotine has been shown to decrease reaction time and increase a
nticipatory responses in a five-choice serial reaction time task (5-CSRTT)
in rats, but the receptor mechanisms mediating this effect remain unknown.
Objectives: To evaluate further the effects of nicotine in this task and to
characterise the receptors mediating these effects. Methods: Using a stand
ard 5-CSRTT protocol, rats were trained to respond to a 0.5-s visual stimul
us, which was reduced to 0.25 s for experimental sessions to induce a perfo
rmance decrement. The effects of acute (0.03-0.3 mg/kg IF) and repeated (0.
1 and 0.3 mg/kg IP for 5 days) nicotine were studied, as was the ability of
mecamylamine (1 mg/kg IF), hexamethonium (5 mg/kg IF), dihydro-beta-erythr
oidine (6 mg/kg IF) and methyllycaconitine (10 mg/kg IF) to antagonise the
effects of acute nicotine. Results: Nicotine had no effect on accuracy, but
decreased response latencies, improved performance in the less-well attend
ed stimulus locations and increased inappropriate responding after both acu
te and repeated treatment. The data suggest that nicotine improves readines
s to respond and improves target scanning, and decreases the ability to wit
hhold premature responses (i.e. increased impulsivity). Except for the redu
ction in error latency, all of the effects of nicotine were antagonised by
the non-selective, centrally acting antagonist mecamylamine, whereas the pe
ripheral antagonist hexamethonium had no effect, demonstrating that nicotin
e's actions are central in origin. Dihydro-beta-erythroidine, a competitive
nicotinic antagonist, antagonised all of the effects of nicotine. In contr
ast, the a, antagonist methyllycaconitine had no significant effects agains
t nicotine. Conclusions: These results demonstrate that the alpha(7) recept
or subtype is not involved in the effects of nicotine in the 5-CSRTT and th
at its effects are more likely to be mediated by a receptor(s) such as alph
a(4)beta(2), alpha(4)beta(4) and/or alpha(3)beta(2) which is sensitive to a
ntagonism by dihydro-beta-erythroidine.