Scopolamine impairs behavioural function and arginine metabolism in the rat dentate gyrus

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive memory loss. It has been shown that the cholinergic neurotransmission deficit is one of the neurochemical characteristics of AD, and that l-arginine and its metabolites also play a prominent role in AD pathogenesis. Scopolamine, a non-selective muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs behavioural function, including learning and memory. This study investigated the effects of scopolamine on animals’ behavioural performance and l-arginine metabolism in the hippocampus and prefrontal cortex. Rats were given intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and tested in the Y-maze, open field, water maze and elevated plus maze 30 min post-treatment. After completion of the behavioural testing, the CA1, CA2/3 and dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were harvested to measure the activity and protein expression of nitric oxide synthase (NOS) and arginase, and the levels of l-arginine, l-citrulline, l-ornithine, agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine treated rats displayed reduced alternation and exploratory behaviour, increased swimming speed and impaired spatial learning and memory. There were significantly decreased NOS activity, increased arginase activity, and increased l-ornithine and putrescine levels in the DG, but not other regions examined, in the scopolamine treated rats as compared to the controls. These findings suggest that scopolamine impairs behavioural function and alters l-arginine metabolism in the DG sub-region of the hippocampus specifically. The underlying mechanisms of it remain to be explored further.