Alzheimer’s disease (AD) is a common progressive neurodegenerative disorder with still largely unknown etiopathology. Several lines of experimental data support a strong relationship between the disorder and an excessive brain accumulation of β-amyloid peptides (βA) in extracellular senile plaques. In the present study, effects of βA 25-35, which is thought to be the active site of βA, on membrane and action potentials in addition to postsynaptic potentials evoked by stimulating the external capsule were studied in basolateral amygdaloid slices from halothane-anaesthetized Wistar rats’ (80-90 g), using an in vitro intracellular recording technique (Yajeya et al. 2000). All experiments strictly conformed to national guidelines and the rats were humanely killed. Results were compared using Student’s paired t test and all changes found were statistically significant (P < 0.05).

Bath application of βA 25-35 (800 nM, 1.2 µM) resulted in depolarization or hyperpolarization of membrane potential averaging 9.18 ± 4.18 mV and 6.5 mV, respectively. No changes occurred when the experiments were performed on slices previously perfused with the selective Na⁺ channel blocker tetrodotoxin (TTX). On the other hand, application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the selective antagonist for NMDA receptors 2-amino-5-phosphopentanoic acid (APV), followed by βA 25-35 did not affect the membrane potential. The aforementioned results suggest that βA 25-35 actions were not generated through its effect on the postsynaptic membrane. As far as postsynaptic potentials (elicited by stimulating the external capsule) are concerned, we found that perfusion of βA 25-35 (800 nM) induces a significant decrease (75 ± 2% reduction in relation to control) of the amplitude of postsynaptic potentials, especially the excitatory postsynaptic potentials (EPSP), in a time-dependent manner. With the aim of determining the location of all βA 25-35 actions, we used a paired-pulse protocol measured at 60 ms intervals and compared the ratio of the first pulse in relation with the second (S₂/S₁). The fact that βA 25-35 decreased PPF (from 33.24% control to 5.37%) through bath application is concomitant with a presynaptic mode of action. The contribution of α-7 nicotinic receptors was evaluated through application of methyllycaconitine (100 µM) together with β-amyloide (800 nM). β-Amyloide depressed the amplitude of EPSP indicating that α-7 nicotinic receptors are not involved in the action mechanisms of the peptide.

The results obtained so far provide evidence that βA 25-35 actions are fundamentally related to modulatory effects on neurotransmission within amygdala.

This work was supported by grants PBI 2000-11900 (DGICYT), 01/0385 (FIS) and a fellowship from AECI (Agencia Española de Cooperación Internacional).