Anatomical evidence indicates that medial prefrontal cortex (mPFC) neurons project to the dorsal raphe nucleus (DR). In this study, we functionally characterized this descending pathway in rat brain. Projection neurons in the mPFC were identified by antidromic stimulation from the DR. Electrical stimulation of the mPFC mainly inhibited the activity of DR 5-HT neurons (55 of 66). Peristimulus time histograms showed a silence of 150 +/- 9 msec poststimulus (latency, 36 +/- 1 msec). The administration of WAY-100635 and picrotoxinin partly reversed this inhibition, indicating the involvement of 5-HT(1A) and GABA(A) receptors. In rats depleted of 5-HT with p-chlorophenylalanine, the electrical stimulation of mPFC mainly activated 5-HT neurons (31 of 40). The excitations (latency, 17 +/- 1 msec) were antagonized by MK-801 and NBQX. Likewise, MK-801 prevented the rise in DR 5-HT release induced by electrical stimulation of mPFC. The application of 8-OH-DPAT in mPFC significantly inhibited the firing rate of DR 5-HT neurons and, in dual-probe microdialysis experiments, reduced the 5-HT output in mPFC and DR. Furthermore, the application of WAY-100635 in mPFC significantly antagonized the reduction of 5-HT release produced by systemic 8-OH-DPAT administration in both areas. These results indicate the existence of a complex regulation of DR 5-HT neurons by mPFC afferents. The stimulus-induced excitation of some 5-HT neurons by descending excitatory fibers releases 5-HT, which inhibits the same or other DR neurons by acting on 5-HT(1A) autoreceptors. Afferents from the mPFC also inhibit 5-HT neurons through the activation of GABAergic interneurons. Ascending serotonergic pathways may control the activity of this descending pathway by acting on postsynaptic 5-HT(1A) receptors.

Theoretical models and ab initio Hartree-Fock wave functions are used to investigate the N 1s core level binding energies of N-containing calcined carbonaceous materials. Comparison of calculated and experimental values for a series of test molecules reveals that the N 1s core level shift from one compound to another is mainly originated by initial state effects. This permits a systematic study of different situations and allows establishment that three different types of nonoxidized N atoms can be present in these materials. These are "pyridinic", "pyrrolic", and "graphitic" nitrogen with binding energies of ≈399.0, ≈400.3, and ≈401-403 eV, respectively. This assignment is in very good agreement with a recent experimental X-ray photoelectron spectra on petroleum cokes and demonstrates, for the first time, that it is possible for N to exhibit rather large core level 1s energies without requiring the presence of any charge transfer from N-oxide groups. Theoretical reasons for such a behavior are also given.

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