A study of the nicotinic agonist SIB-1553A on locomotion and attention as measured by the five-choice serial reaction time task.

SIB-1553A is a novel ligand with reputed agonist selectivity at nicotinic receptors containing the beta(4) subunit. As such, it represents an interesting pharmacological tool with which to probe the function of nicotine receptor subtypes. In the present studies, we compared SIB-1553A with nicotine in its ability to stimulate locomotion and to enhance attention in rats as assessed using the five-choice serial reaction time task (5-CSRTT). In nicotine-naive rats, SIB-1553A (10-40 mg/kg) induced a comparable increase in locomotion to nicotine (0.4 mg/kg), whereas in nicotine-sensitised rats, an enhanced locomotor response was seen to nicotine (0.4 mg/kg) but not to SIB-1553A (10-80 mg/kg). Similarly, chronic treatment with either SIB-1553A or nicotine did not lead to a cross-sensitised locomotor response. Unlike nicotine, SIB-1553A-induced locomotion was insensitive to antagonism by either mecamylamine (1 mg/kg) or DH beta E (3 mg/kg), suggesting a non-nicotinic mechanism. In young and aged rats, nicotine (0.4 mg/kg) enhanced attention as demonstrated by an increase in response accuracy and speed. SIB-1553A (3-10 mg/kg) did not mimic any of these changes and at the highest dose tended to disrupt performance. These results lend further support to the involvement of a high affinity site, possibly alpha(4)beta(2), in the locomotor and attentional-enhancing properties of nicotine.