Volume transmission of beta-endorphin via the cerebrospinal fluid; a review

There is increasing evidence that non-synaptic communication by volume transmission in the flowing CSF plays an important role in neural mechanisms, especially for extending the duration of behavioral effects [1-4]. Beta-Endorphin (β-END) is a neuropeptide, produced by pro-opio-melanocortin (POMC) neurons as well as by pituitary cells mainly located in the intermediate lobe [5,6], by cleavage from a larger precursor molecule, beta-lipotropin. β-END is its C-fragment (containing the amino acids 61–91) and was characterized by Guillemin et al, in 1977 [7,8], in combination with its sister peptides, α-melanocyte-stimulating hormone (α-MSH), adrenocorticotropic hormone, (ACTH) and other substances [9-13]. The molecular weight of β-END is 3465 g/mol.The behavioral effects of β-END were soon recognized and vary from prolonged muscular rigidity [14] to general arousal [15]. More specifically, β-END was shown to play a role in several kinds of behavior, like feeding [16-18], sexual behavior [19,20], learning processes [21,22], reward [23,24], pain-regulating mechanisms [25-31], as well as in a variety of physiological functions such as cardiovascular regulation [32,33] and stress responses [12,34-37].Interestingly, β-END is produced in the pituitary for release into the peripheral systemic circulation, and by hypothalamic POMC neurons for release inside the central nervous system (CNS). Since it has been observed that peripheral administration of β-END does not necessarily induce the same effects as intracerebroventricular (icv) administration, this suggests the existence of two functionally different β-END systems, one for the central effects and one for the peripheral effects. The present review explores the existence of a special central and brain-directed β-END system and the possibility that the cerebrospinal fluid (CSF) plays a special role in the propagation of these brain-directed β-END messages.The evidence discussed in the present review has led to the conclusion