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Neuroprotective Effect of Ceftriaxone and Selegiline on Scopolamine Induced Cognitive Impairment in Mice

Glutamate is the principal excitatory neurotransmitter in the nervous system. Inactivation of synaptic glutamate is handled by the glutamate transporter GLT1 (Excitatory Amino Acid Transporter EAAT), the physiologically dominant astroglial protein, while its dysfunction may contribute to this neurodegenerative disorders like Alzheimer's disease (AD). It is characterized by a gradual decline in memory associated with shrinkage of brain tissue, with localized loss of neurons mainly in the hippocampus and basal forebrain, with glutamate induced excitotoxicity related oxidative stress in association with diminished level of central cholinergic neurotransmitter-Acetylcholine. Glutamate transporters are important in preventing glutamate oxidative neurotoxicity. In the present study, the effects of ceftriaxone, selegiline and co-administration of these drugs on scopolamine induced learning and memory impairments in mice were studied. Using Rectangular maze test, Morris water maze test, Locomotor activity, Pole climbing tests and Various biochemical parameters such as acetylcholinesterase, TBARS assay, catalase activity and DPPH assay, we discovered that co-administration of ceftriaxone ( -lactam antibiotics which are potent stimulators of GLT1 expression) and selegiline (antioxidant) in mice exerts synergistic potent cognitive-enhancing activity than individually through both anti- acetylcholinesterase and antioxidant mechanisms. The memory enhancing capacity of the drugs were very significant when compared to negative control (p<0.001). Donepezil was used as standard drug.