Norepinephrine (NE)-induced, long-lasting facilitation of the perforant path evoked population spike amplitude in the dentate gyrus (DG) has been reported to occur following iontophoresis of norepinephrine in the DG in vivo and following application of 10 or 20 microM NE to the hippocampal slice in vitro. The present study employs glutamatergic activation of the locus coeruleus (LC) to induce NE release in the DG. Thirty-three female rats served as subjects. The perforant path-evoked potential was elicited once every 10 s and monitored in the DG cell body layer. Following appropriate control periods, 100-150 nL of 0.5 M l-glutamate were pressure ejected in the vicinity of the LC. All placements in or within 300 microM of the LC produced significant facilitation (140%) of the population spike amplitude. Facilitation lasted more than 20 min in 37% of the animals tested. The facilitation effects on population spike amplitude were replicated with up to four ejections of glutamate at the same site. Propranolol (30 mg/kg i.p.) blocked this facilitation of population spike amplitude. Changes in EPSP slope were variable. Glutamate-activation of LC was not accompanied by blood pressure increases. These data suggest that physiological NE release via LC activation induces a beta receptor mediated facilitation of the perforant path-evoked population spike which parallels that obtained with direct application of NE to the DG in vivo or in vitro. LC-NE may provide one mechanism in the mammalian brain for long-lasting heterosynaptic modulation of neural inputs.