Glutamate-dependent regulation of cholinergic phenotype in hypothalamic neurons.

Glutamate NMDA receptor antagonists are used clinically. However, they have serious side effects, some of which are presumably due to an increase in acetylcholine transmission. Our previous experiments revealed acetylcholine-dependent excitation in rat hypothalamic cultures after a chronic glutamate receptor blockade. Dextromethorphan, amantadine, and eliprodil are NMDA receptor antagonists. Lamotrigine inhibits synaptic glutamate release. These drugs are used clinically. Here, using calcium imaging and immunocytochemistry, we demonstrate that a chronic treatment with each of these drugs induced acetylcholine activity and choline acetyltransferase immunoreactivity in rat hypothalamic (but not cortical) cultures. These data support the possibility that some side effects of anti-glutamate drugs in vivo may be due to the increase in cholinergic properties in certain regions of the CNS.