ACTH and enkephalin axonal input to paraventricular neurons containing c-fos-like immunoreactivity.

The presence of c-fos like protein in neuronal nuclei has been observed in several areas of the central nervous system. It is associated with activation of these neurons by specific stimuli, in particular stressful stimuli. The present study investigated the expression of c-fos-like immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus following stimulation of small diameter, nociceptive afferents in the hindfoot of the rat. The afferent innervation to these c-fos containing PVN neurons was examined in order to identify putative neurotransmitters which might modulate the activity of stress responsive, i.e. c-fos containing neurons in the PVN. Adrenocorticotropic releasing hormone (ACTH), enkephalin (ENK), and corticotropin releasing factor (CRF), peptides whose functions have been related to the regulation of stress behavior, were selected to investigate their potential innervation of c-fos immunolabeled neurons. Analysis of immunocytochemically double-labeled vibratome and semi-thin plastic-embedded sections revealed that ACTH and ENK immunoreactive axonal varicosities were present in close anatomical proximity to a substantial number of parvocellular PVN neurons that contained c-fos in response to noxious stimulation. Few c-fos containing PVN neurons were apposed by CRF axonal varicosities. The resulting data show that a large number of c-fos immunoreactive PVN neurons, though not the majority, is innervated by ACTH and ENK. This suggests that the activity of stress responsive, c-fos expressing neurons can substantially be modulated and regulated by ACTH and ENK and to a lesser degree by CRF.