Differential effects of MK-801 on brain-derived neurotrophic factor mRNA levels in different regions of the rat brain.

We have studied the effects of MK-801, a noncompetitive antagonist of N-methyl-D-aspartate-type glutamate receptors, on brain-derived neurotrophic factor (BDNF) mRNA levels in the rat brain. MK-801 decreased BDNF mRNA in the hippocampus and in the superficial layers of the cerebral cortex. However, in single cells of the middle layer of the cerebral cortex and the midline thalamic nuclei BDNF mRNA levels were markedly increased by MK-801. The highest density of these cells was found in the limbic cortex, especially in the retrosplenial and medial entorhinal cortex. Pentobarbital (an enhancer of gabaergic functions) and scopolamine (a muscarinic receptor antagonist) blocked the effects of MK-801 on BDNF mRNA levels in the retrosplenial cortex, but the nicotinic and dopaminergic receptor antagonists mecamylamine and haloperidol, respectively, were ineffective. Pilocarpine, a muscarinic cholinergic agonist increased BDNF mRNA in some, but not all, cortical areas, where MK-801 had elicited an increase in BDNF mRNA. Thus, the observations made with MK-801 demonstrate that depending on the neuronal connections and the transmitter systems involved, a given compound can elicit either a decrease or an increase in BDNF mRNA levels. This may open up pharmacological possibilities to a regionally more refined regulation of the neurotrophin synthesis.