Abstract

SIB-1765F ([±]-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine fumarate) is a novel nicotinic acetylcholine receptor (NAChR) agonist displaying a different in vitro pharmacological profile than nicotine and epibatidine, suggestive of NAChR subtype selectivity. Our study describes the effects of SIB-1765F on locomotor activity in rats, which were compared to those observed for nicotine and epibatidine. The three NAChR agonists decreased or increased locomotor activity in rats naive or habituated to the test apparatus, respectively. The transient reduction in locomotor activity induced by SIB-1765F was quantitatively similar to those induced by nicotine and epibatidine but, unlike the effects of nicotine and epibatidine, was not blocked by the NAChR antagonists mecamylamine and dihydro-β-erythroidine, suggesting different mechanisms of action. Furthermore, SIB-1765F produced a larger and longer-lasting increase in locomotor activity when administered to rats familiar with the test apparatus. Mecamylamine and dihydro-β-erythroidine but not hexamethonium blocked the increase in locomotor activity induced by SIB-1765F, suggesting that SIB-1765F elicits this effect predominantly through the activation of central NAChR. The SIB-1765F-induced increase in locomotor activity was also attenuated by selective D1 and D2 dopamine receptor antagonists, implying that this increase in locomotor activity is mediated through the activation of dopamine receptors subsequent to the release of dopamine. Based on these results, SIB-1765F appears to have a different locomotor activity profile than nicotine and epibatidine.