AT LEAST 3 NEUROTRANSMITTER SYSTEMS MEDIATE A STRESS-INDUCED INCREASEIN C-FOS MESSENGER-RNA IN DIFFERENT RAT-BRAIN AREAS

1. Protooncogene c-fos mRNA levels were determined in the rat cerebral cortex, hippocampus, and cerebellum after exposure to a combined forc ed swimming and confinement stress. The stress resulted in an increase in c-fos mRNA levels in all three brain areas. 2. In an effort to elu cidate the neurotransmitter systems involved in this stress-induced in crease, animals were injected, prior to exposure to the stress, with e ither diazepam, MK-801, or propranolol. 3. In both the cerebral cortex and the hippocampus the stress-induced increase in c-fos mRNA was inh ibited by MK-801, suggesting that it is mediated via NMDA receptors. I n the hippocampus, propranolol had a similar effect, indicating that b eta-adrenergic receptors are also involved in the stress-induced incre ase in c-fos mRNA. 4. On the other hand, the increase in c-fos mRNA pr oduced by the stress of the injection was inhibited in the cerebral co rtex by diazepam or propranolol and in the hippocampus only by diazepa m. Furthermore, administration of MK-801 resulted in an increase in c- fos mRNA in the hippocampus of the nonstressed animals. In the cerebel lum no one of the three drugs employed affected c-fos mRNA levels in e ither stressed or nonstressed animals. 5. Our results thus show that v arious forms of stress activate, in different brain areas, neurons wit h either NMDA, beta-adrenergic, and/or GABA-A receptors.