ABSTRACT
Epilepsy is a neurological disorder associated with excitatory and inhibitory imbalance within the underlying neural network. This study evaluated inhibitory γ-amino-butyric acid (GABA)ergic modulation in the CA1 region of the hippocampus of male Wistar rats and Wistar audiogenic rats (aged 90 ± 3 days), a strain of inbred animals susceptible to audiogenic seizures. Field excitatory postsynaptic potentials and population spike complexes in response to Schaffer collateral fiber stimulation were recorded in hippocampal slices before and during application of picrotoxin (50 µM, 60 min), a GABA A antagonist, and the size of the population spike was quantified by measuring its amplitude and slope. In control audiogenic-resistant Wistar rats (N = 9), picrotoxin significantly increased both the amplitude of the population spike by 51 ± 19 percent and its maximum slope by 73 ± 21 percent. In contrast, in slices from Wistar audiogenic rats (N = 6), picrotoxin caused no statistically significant change in population spike amplitude (33 ± 46 percent) or slope (11 ± 29 percent). Data are reported as means ± SEM. This result indicates a functional reduction of GABAergic neurotransmission in hippocampal slices from Wistar audiogenic rats.
Subject(s)
Animals , Male , Rats , CA1 Region, Hippocampal/drug effects , Epilepsy/metabolism , GABA Antagonists/pharmacology , Picrotoxin/pharmacology , Synaptic Transmission/drug effects , gamma-Aminobutyric Acid/metabolism , CA1 Region, Hippocampal/metabolism , Neural Inhibition/drug effects , Neural Inhibition/physiology , Rats, Wistar , Synapses/drug effects , Synapses/physiologyABSTRACT
Background & objectives: Acetylcholinesterase inhibitors (AChE-Is) are used for the treatment of Alzheimer’s disease (AD). These drugs including galanthamine have been shown to modulate synaptic activity in hippocampus and improve memory processes. Although Tabernaemontana divaricata extract (TDE) has been used as traditional medicine for various pharmacological effects, its effect in enhancing cholinergic activity provides additional benefit to its known effects. We investigated whether TDE can modulate the synaptic function in hippocampus and compared its effects to those of galanthamine. Methods: Hippocampal slices were prepared from male wWistar rats, functional effects of TDE were characterized by using pharmacological tools and extracellular recordings of field excitatory postsynaptic potentials (fEPSPs). Results: TDE significantly reduced fEPSPs. The fEPSPs reduction was prevented by atropine, but not pancuronium. These TDE effects were similar to those of galanthamine. Interpretation & conclusions: Our findings indicate that TDE can effectively modulate synaptic responses in the hippocampus similar to galanthamine, suggesting that this traditional medicine could be beneficial in ageing with ACh deprivation in the brain.