Previously, our studies in freely-moving rats demonstrate that the probability, magnitude and longevity of LTP at the medial perforant path-dentate gyrus (DG) synapse are increased when LTP is induced in a novel environment (Davis Hart, SFN,1997). Our studies also indicate this facilitation effect elicited by novelty is independent from beta-adrenergic and muscarinic receptor mediation (Davis Hart, SFN, 2000). However, exposure to novel stimuli activates other neuromodulatory systems, including the serotonergic system (Wilkson, Everitt, 1996). We therefore examined whether the serotonergic system , specifically 5-HT1A receptors, are involved in novelty-induced facilitation of LTP. Perforant path-DG responses were collected daily for 1 week in the home cage until stable baseline responses were established. Following a 15 min collection of baseline responses in the home cage, a selective 5-HT1A receptor antagonist, WAY-100635 (0.5mg/kg, 0.01mg/kg or 0.005mg/kg) or equal volumes of water were administered i.p...