Behavioral effects of PNU-282987, an alpha7 nicotinic receptor agonist, in mice

The cholinergic system is closely related to learning and memory processes, and its neurodegeneration seems to be involved in neurodegenerative and neuropsychiatric cognitive disorders in the elderly. Alpha7 nicotinic acetylcholine receptors (nAChRs) have recently been shown to mediate neuroprotection and enhance cognitive performance in a variety of tasks, suggesting that there may be a new target for the pharmacotherapy of cognitive deficiencies. In this study, we investigated the behavioral effects of the acute and sub-chronic administration of 0, 1, 3, and 5 mg/kg of PNU-282987 (PNU) on motor activity, anxiety and learning in open-field and Morris water maze tasks in mice. Our results showed that the highest dose of PNU (5 mg/kg) diminished motor activity in the open-field following 5 and 12 days of administration (acute and sub-chronic, respectively). No effects on the acquisition of the Morris water maze were observed. However, only 1 mg/kg of PNU administered just before training trials over a period of 5 days showed beneficial effects on the retention of the water maze when evaluated 4 h after water maze acquisition. Further studies are needed to clarify the effects on the cognitive performance and potential neuroprotection of these agents in an elderly population with slight or severe deficiency in learning and memory processes, and/or in animal models vulnerable to neurodegenerative disorders.

Research highlights▶ Acute and sub-chronic PNU-282987 at a dose of 5 mg/kg diminished motor activity. ▶ PNU-282987 has no effects on spatial learning acquisition. ▶ 1 mg/kg of PNU-282987 improve retention in the water maze.