Imidazoline 1 receptor activation modulates central pain perception and behaviour in metabolic syndrome rats

Metabolic syndrome (MetS) plays a critical role in the development of neurodegenerative and behavioral disorders, including dementia, learning and memory defects, mood disorders, and anxiety. In MetS, nerve damage can result in altered pain perception. Imidazoline-1 receptor (I1R) is known to have neuroprotective properties; however, its role in MetS-associated behavioral alterations and central pain perception remains poorly studied. In this study, MetS was induced in rats by administering 10% fructose in drinking water and a 3% salt-enriched diet for 12 weeks. Rats received I1R agonist, moxonidine (6 mg/kg/day, p.o) during the final two weeks of the experiment. Three days before euthanasia, all rats underwent behavioral testing: the hot plate test to evaluate central pain perception, the Y maze test to investigate spatial working memory, the elevated plus maze (EPM) to assess anxiety-like behavior, and the open field test (OFT) to evaluate exploratory activity. MetS rats displayed increased latency in the hot plate test, indicating impaired pain perception. They also exhibited impairment in spatial working memory (lower spontaneous alternation performance), reduced exploratory activity (fewer crossings in the OFT), and increased anxiety-like behavior (higher number of entries into the closed arms of the EPM). Treatment with moxonidine improved pain perception, enhanced spatial working memory, and reduced anxiety-like behavior in MetS rats. These findings highlight the therapeutic potential of I1R activation in improving central pain perception and spatial working memory while reducing anxiety-like behavior under MetS conditions.