Long-term Ceftriaxone exposure modulates neuroplasticity in hippocampus.

The glial glutamate transporters play a crucial role in clearing glutamate from the synaptic space, thereby regulating its concentration and maintaining synaptic homeostasis. As the main glutamate transporter in astrocytes, GLT-1 ensures efficient neurotransmitter clearance, contributing to the excitatory-inhibitory balance in neural circuits. Given its essential role in synaptic function, modulation of GLT-1 has been explored as a potential approach to altering synaptic transmission and plasticity. The objective of this study was to examine hippocampal synaptic plasticity in juvenile rats following the administration of Ceftriaxone (CTX), a compound widely reported to influence GLT-1 function and glutamate homeostasis. Our study primarily focused on functional electrophysiological outcomes rather than direct molecular measurements. A 0.5 μl intracerebroventricular (ICV) microinjection of 0.5 mM Ceftriaxone, a compound widely reported to influence GLT-1 function and glutamate homeostasis, was administered to male Wistar rats. Field excitatory postsynaptic potentials (fEPSP) were recorded from the CA1 region following Schaffer-collateral stimulation. The study found that 29 days of CTX treatment significantly weakened long-term potentiation (LTP) in CA3-CA1 synapses. A significant decrease in the paired-pulse index was observed following ceftriaxone injection at inter-pulse intervals (IPI) of 20 and 80 milliseconds. Compared to the control group, the Ceftriaxone-treated group showed a significantly higher maximum current intensity required to elicit the maximal synaptic response. This study suggests that, beyond its antimicrobial properties, Ceftriaxone can significantly influence electrophysiological properties in the hippocampus. Such findings highlight the significant impact of ceftriaxone on synaptic function and suggest its potential to modulate neural network activity.