The CA1 to perirhinal cortex projection is one of multiple hippocampal-neocortical projections considered to be involved in memory consolidation. This projection has been shown to sustain long-term potentiation (LTP) following stimulation of CA1. Here we examined the pharmacological properties underpinning the plasticity observed in this projection. A stimulating electrode was inserted into the area CA1 and a recording electrode was inserted into the perirhinal cortex of urethane-anaesthetised Wistar rats. Rats (n = 6 in each drug group) were administered with either saline (0.09%), MK-801 (NMDA antagonist; 0.1Â mg/kg) or CNQX (AMPA/kainate antagonist; 1.5Â mg/kg). Baseline recordings were made for 10Â min by stimulating area CA1 (0.05Â Hz stimulation protocol). High-frequency stimulation (HFS; 250Â Hz) was performed and post-HFS fEPSP recordings were made for 1Â h (0.05Â Hz, as above). Baseline and post-HFS paired-pulse facilitation (PPF) recordings were performed across six different interpulse intervals. CA1 and perirhinal cortex tissue samples were taken from the stimulated and unstimulated hemispheres of each rat brain and analysed using a brain-derived neurotrophic factor (BDNF) ELISA. Results indicate that LTP was induced in the saline and MK-801 groups but not in the CNQX group; fEPSPs in the latter group rapidly returned to baseline levels following a short period of post-tetanic potentiation. Drug treatment and HFS had no effect on PPF levels. Drug treatment significantly reduced concentrations of both CA1 and perirhinal BDNF and prevented stimulation-induced increases in BDNF in CA1. This molecular and electrophysiological data suggests that LTP in the CA1-perirhinal cortex projection may require activation of postsynaptic AMPA/kainate receptors in order to sustain LTP. Â© 2009 Elsevier B.V. All rights reserved.