Septohippocampal cholinergic neurons are regulated trans-synaptically by endorphin and corticotropin neuropeptides.

The content of acetylcholine (ACh) in nerve terminals or the dorsal hippocampus was examined after intraventricular, intraseptal, or intrahippocampal administration of a variety of endorphin/corticotropin neuropeptides. beta-Lipotropin, alpha-endorphin, gamma-endorphin, alpha-melanotropin, beta-melanotropin, adrenocorticotropin-1-39 (ACTH1-39), and ACTH4-10 (1, 3, 10, or 30 micrograms each) did not affect levels of ACh in the hippocampus 30 min after injection into the lateral ventricle. beta-Endorphin, administered intraventricularly (1, 3, 10, or 30 micrograms) or intraseptally (1 microgram), increased levels of ACh, while ACTH1-24, injected similarly, decreased levels of the neurotransmitter. ACh concentrations remained unchanged after direct application of beta-endorphin or ACTH1-24 (1, 3, 10, of 30 micrograms each) into Ammon's horn. Acute unilateral transection of the fimbria/superior fornix resulted in a time-related decrease in hippocampal ACh concentrations. Levels of ACh did not change 1 hr after transection; however, concentrations of hippocampal ACh decreased significantly 1 d or 1 week after deafferentation. ACh levels in the contralateral hippocampus remained unaffected at all times tested. Fimbrial transection blocked fully both endorphin- and corticotropin-induced changes in hippocampal ACh after the neuropeptides were injected into the lateral ventricle or the septal region. Naloxone, which, after subcutaneous (1 mg/kg) or intraventricular (100 micrograms) injection alone, failed to change levels of hippocampal ACh, antagonized the effects of intraventricular or intraseptal beta-endorphin or ACTH1-24 or hippocampal ACh levels. The results suggest a site of endorphin/corticotropin receptor interaction at the level of cholinergic cell bodies in the septal region for regulating the activity of septohippocampal cholinergic neurons.

Immunoreactive dynorphin in mammalian spinal cord and dorsal root ganglia.

The distribution of immunoreactive dynorphin (ir-dynorphin) has been determined in dorsal and ventral aspects of spinal cord and in dorsal root ganglia of rabbit and rat. Concentrations are highest in dorsal root, with intermediate levels in ventral cord and low levels in dorsal root ganglia of both species. Levels of ir-dynorphin are relatively uniform over examined segments (vertebrae C2-S3) of rabbit spinal cord and dorsal root ganglia. Gel permeation chromatography of extracts from rabbit dorsal and ventral spinal cord and dorsal root ganglia revealed at least three immunoreactive components of differing molecular size in all three structures. Multiple unilateral or bilateral dorsal rhizotomy (vertebrae C5-T1) in rat did not affect levels of ir-dynorphin in spinal cord. As reported [Goldstein, A. & Ghazarossian, V. E. (1980) Proc. Natl. Acad. Sci. USA 77, 6207-6210], midthoracic spinal transection was without effect. Within the spinal cord, the neuropeptide appears, most probably, to be contained in short-axoned neurons. We surmise that this potent opioid peptide may participate in the processing of sensory information in spinal cord.

Corticotropin regulates transsynaptically the activity of septo-hippocampal cholinergic neurones.

The activity of septo-hippocampal neurones is affected by the action on cholinergic perikarya in the septum of a variety of putative neurotransmitters, including substance P and beta-endorphin. (The latter is released in the septal region from neurones which originate in the medial basal hypothalamus.) It has also been reported that two other neuropeptides, corticotropin (ACTH1-24) and alpha-melanotropin (alpha-MSH), affect acetylcholine turnover in septo-hippocampal neurones in a manner that is not blocked by transection of the afferents to the hippocampus, from which it has been inferred that the neurotransmitters act directly on the hippocampus. We now describe experiments with corticotropin which show that the effect is rather the influence on septo-hippocampal cholinergic neurones of peptidergic neurones within the septum.