The effects of peripheral D-amphetamine, 4-OH amphetamine, and epinephrine on maintained discharge in the locus coeruleus with reference to the modulation of learning and memory by these substances.

D-Amphetamine, 4-OH amphetamine, and epinephrine have been shown in many behavioral studies to facilitate memory when given post-training. The effect of these drugs on the maintained discharge of cells in the locus coeruleus (LC) was investigated using a route of administration (intraperitoneal) and a log-dose range of these drugs comparable to those used in the behavioral experiments. D-Amphetamine profoundly suppressed maintained discharge: an inhibitory effect was observed at every dose (0.1, 1.0, 10.0 mg/kg). In contrast, only the highest dose of 4-OH amphetamine (8.2 mg/kg) inhibited activity in the LC, and this effect was a modest one. Unlike the amphetamines, epinephrine (500 micrograms/kg) elevated maintained discharge. These results are discussed in the context of the hypothesized involvement of the LC in the enhancement of memory by these drugs.