Long-term potentiation (LTP) is an example of activity-dependent plasticity that was discovered in the hippocampal formation. There is growing evidence that LTP not only is a useful model for mnemonic processes, but also may represent the cellular substrate for at least some kinds of learning and memory. The hippocampal slice preparation has proven exceptionally useful in pharmacological studies of possible mechanisms of LTP. A slice remains viable and stable for several hours, and known concentrations of drugs in the bathing medium can be added and then washed out. Drugs can also be applied under visual guidance from micropipettes to discrete neuronal regions, an accomplishment that is aided by the lamellar organization of the hippocampus. Electrical stimulation of the perforant path (PP) in the molecular layer of the dentate gyrus produces a monosynaptic excitatory postsynaptic potential (EPSP) and action potential, which can be recorded extracellularly as a population EPSP and population spike, respectively. Presentation of a high-frequency train (HFT; 100 Hz X 1 s) to the PP results in a long-lasting (greater than 30 min) potentiation of the maximal EPSP slope and of the population spike amplitude. Similarly, exposure of the slice to norepinephrine (e.g. 20 microM for 30 min) results in a long-lasting potentiation (LLP) of both EPSP and population spike (Stanton and Sarvey (1987) Brain Res. Bull., 18: 115). No such LLP was seen in field CA1 following NE application (Stanton and Sarvey (1985) Brain Res., 361: 276). beta-Adrenergic antagonists, such as propranolol, inhibit both LTP and NE-induced LLP in dentate (Stanton and Sarvey, J. Neurosci., 5: 2169 (1985); Stanton and Sarvey (1985) Brain Res., 361: 276). Cyclic AMP levels are increased by either an HFT or NE (Stanton and Sarvey (1985) Brain Res., 358: 343). Thus, NE, acting through a beta-receptor, appears to be both necessary and sufficient to produce long-lasting enhancement of synaptic responses. Finally, inhibitors of protein synthesis, such as emetine, also block both LTP and NE-induced LLP (Stanton and Sarvey, J. Neurosci., (1984) 4: 3080; Stanton and Sarvey (1985) Brain Res., 361: 276). The N-methyl-D-aspartate (NMDA) excitatory amino acid receptor subtype appears to play a role in a number of forms of neuronal plasticity. Bath-application of a 1 microM concentration of the NMDA antagonists D-2-amino-5-phosphonavaleric acid (AVP) or 3-((+/-)2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) blocked both LTP and NE-induced LLP in the dentate gyrus.(ABSTRACT TRUNCATED AT 400 WORDS)