Norepinephrine promotes long-term potentiation in the adult rat hippocampus in vitro

We previously found a reduction in the ability of a single 100 Hz x 1 sec tetanus to induce long-term potentiation (LTP) in the CA1 region of hippocampal slices prepared from adult animals. To determine whether this reduction in LTP generation results from changes in neuromodulator function, we examined the ability of several neuromodulators to promote LTP in slices prepared from mature rats. Although acetylcholine, N-methyl-D-aspartate, and an agonist at metabotropic glutamate receptors failed to promote LTP, administration of norepinephrine allowed robust LTP. The effects of norepinephrine were mimicked by an alpha1-adrenergic agonist and were blocked by an alpha1-receptor antagonist. Beta-adrenergic agonists and antagonists were ineffective. These results suggest that norepinephrine acting via alpha1-adrenoceptors may be an important cofactor in promoting lasting synaptic plasticity in the adult central nervous system and that changes in adrenergic function may contribute to maturation- or aging-associated changes in memory function.