Corticotropin-releasing factor stimulates the release of methionine-enkephalin and dynorphin from the neostriatum and globus pallidus of the rat: in vitro and in vivo studies

Abstract

This study examined the changes in the in vitro and in vivo release of methionine-enkephalin (Met-enkephalin) and dynorphin from the rat neostriatum in response to corticotropin-releasing factor (CRF). The levels of each opioid peptide were measured in the same sample collected at each time interval by specific radioimmunoassay methods. The in vitro release experiments were conducted using neostriatal slices (250 μm) obtained from adult male Wistar rats whereas in the in vivo studies, the release of both Met-enkephalin and dynorphin were assessed in push-pull perfusates of the caudate nucleus (containing both Met-enkephalin and dynorphin cell bodies/fibres) and the globus pallidus (containing Met-enkephalin and dynorphin terminals) of chloral hydrate-anaesthetised adult male Wistar rats. In the in vitro studies, CRF (10 −12, 10 −10 and 10 −8 M) (applied in pulses of 75 min) stimulated both Met-enkephalin and dynorphin release from the neostriatal slices in a dose-related manner; in the presence of the CRF receptor antagonist, α-helical CRF 9–14 (10 −16 M) release of both Met-enkephalin and dynorphin in response to CRF (10 −8 M) were completely blocked. Push-pull perfusion experiments conducted in both the caudate nucleus and the globus pallidus, also demonstrated a dose-related increase in the release of both Met-enkephalin and dynorphin in response to CRF (10 −12, 10 −10 and 10 −8 M) applied in 60-min pulses. In addition, in each of the two brain sites, the release of both Met-enkephalin and dynorphin in response to CRF (10 −8 M) was completely blocked by α-helical CRF 9–41 (10 −6 M). Both the in vitro and in vivo studies thus demonstrate that CRF can exert potent effects on Met-enkephalin and dynorphin release within the neostriatum-pallidum of the rat and that such effects are mediated via receptors specific for CRF, probably located on both the cell bodies and terminals of these opioid-containing neurones. The data obtained in this study thus substantiate the view that CRF, in addition to its regulation of pituitary opioid peptides, can communicate to opioid-containing neurones within the central nervous system and that many of the effects elicited by CRF may be ascribed to the opioid peptide released by CRF. The effects of CRF on the activity of Met-enkephalin and dynorphin neurones within the rat neostriatum, two distinct populations of chemically identified striatal projection neurones, suggest that CRF may play an integral role in the regulation of somatic motor processes with relevance to disorders of movement that originate from the basal ganglia.