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 β 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 DHβE (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 α 4β 2, in the locomotor and attentional-enhancing properties of nicotine.