Cholecystokinin in the Medial Parvocellular Subdivision of the Paraventricular Nucleus: Co‐existence with Corticotropin‐releasing Hormone

Discovered in extracts of gut, cholecystokinin (CCK) has also been found in the central nervous system.’-‘ The major form of brain CCK is the octapeptide (CCK-8),5 which seems to be involved in a variety of brain functions because it is present in many regions of the rat Among these regions is the hypothalamus, where CCK is in the hypothalamo-neurohypopyseal system. CCK co-exists with oxytocin in magnocellular cells of the hypothalamic paraventricular (PVN) and supraoptic (NSO) CCK-immunoreactive fibers and terminals have been visualized in the median eminence (ME) and n e u r o h y p o p h y s i ~ . ~ ~ ~ ~ ~ ~ ’~ Lesioning the PVN results in the disappearance of immunoreactive CCK in the M E and pituitary.’~’’ It has been suggested that this “magnocellular” CCK is involved in the release of oxytocin and probably vasopressin from the posterior pit~itary.‘~’,’’.’’ Recently. a population of CCK-immunoreactive neurons has been described in the medial parvocellular subdivision of the paraventricular nucleus.” The neurons of this subdivision are known to project to the external layer of the ME and to be involved in neuroendocrine reg~1ation.I~ The high levels of CCK in the hypothalamus as well as its presence in the median eminence suggested a possible role for CCK as a releasing factor. I t was shown to stimulate prolactin and growth hormone release under certain conditions. However, due to the high concentrations needed for these effects, it seems unlikely that CCK-8 had a physiological role as a releasing f a ~ t o r . ~ / ~ * ” . ’ ~ Some evidence suggests that it may regulate the activity of corticotrophs, but this is also c o n t r o ~ e r s i a l . ’ ~ ~ ~ The neurons containing the corticotropin-releasing factor” were described in the medial parvocellular region of the paraventricular n u c l e u ~ . ~ ~ ~ ~ ~ Cholecystokinin-immunopositive neurons were described in the same subdivision.” Adrenalectomy results in changes of the CCK-like immunoreactivity in the external zone of the median e m i n e n ~ e . ’ ~ . ~ ~ To study the possible involvement of CCK in regulating adrenocorticotropic hormone (ACTH) release, we decided to see if there was a co-existence of CCK with corticotropin-releasing factor (CRF) in the paraventricular nucleus. Immunocytochemical studies using the avidin-biotin (ABC) techniq~e~’*’~ revealed a large popula-