Formoterol attenuates lipopolysaccharide-induced mnemonic impairment in the delayed nonmatch to position task in rats

The delayed nonmatch to position (DNMTP) task is an instrumental learning paradigm applied to assess higher executive functions including attention and working memory in rats. In this study, the effect of systemic challenge with the acute inflammatory stimulus [lipopolysaccharide (LPS) 0.25 mg/kg, intraperitoneally] was assessed in Wistar rats on performance in the DNMTP task. By means of validation, the effect of treatment with the muscarinic receptor antagonist scopolamine [0.02 mg/kg, subcutaneously (s.c.)], known to disrupt performance in the task, and its reversal by coadministration of the cognitive-enhancing agent and acetylcholinesterase inhibitor donepezil (0.3 mg/kg, s.c.) were confirmed. Sex differences emerged between males' and females' mnemonic response to LPS 24-h postadministration with males showing reduced performance in the DNMTP task at higher working memory loads compared with females. Noradrenaline is an endogenous neurotransmitter with innate anti-inflammatory properties. The impact of targeting the noradrenergic system with the β2-adrenoceptor agonist Formoterol was further assessed on LPS-induced cognitive impairment in the DNMTP task. Coadministration of Formoterol (0.5 mg/kg, s.c.) attenuated LPS-driven mnemonic impairments in males but not females. Overall, the results show the DNMTP task is a paradigm sensitive to acute systemic inflammation and indicate that Formoterol may have useful anti-inflammatory properties in mitigating inflammatory-associated cognitive impairment.