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Published on: April 28, 2016
Behavioral and neuroendocrine actions of the Met-enkephalin-related peptide MERF
E Bujdosó1, M Jászberényi, J Farkas
1Department of Pathophysiology, University of Szeged, Neurohumoral Research Group, Hungarian Academy of Sciences, Szeged, Hungary.
Abstract:
The effects and the mediation of the action of the proenkephalin derivative Met(5)-enkephalin-Arg(6)-Phe(7) (MERF) on the hypothalamo-pituitary-adrenal (HPA) system and open-field behavior were investigated in mice. Intracerebroventricular injection of the heptapeptide increased square crossing, rearing, and plasma corticosterone level. To characterize the receptors involved in these neuroendocrine processes, animals were pretreated either with the nonselective opioid antagonist naloxone or the kappa-antagonist nor-binaltorphimine (nor-BNI). Both antagonists dose-dependently attenuated the HPA activation elicited by MERF. Naloxone also blocked the behavioral responses, but nor-binaltorphimine did not elicit a significant inhibition. The dopamine antagonist haloperidol and a corticotropin-releasing hormone (CRH) antagonist were also preadministered to shed light on the transmission of the actions of MERF. Both the motor responses and the HPA activation were diminished by the preadministration of the CRH antagonist, while haloperidol attenuated only square crossing and rearing. To investigate the direct effect of MERF on the dopaminergic system, dopamine release of striatal slices was measured in a superfusion system. Neither the basal nor the electric impulse-evoked dopamine release was modified by MERF. The results suggest that opioid-mediation predominate in the neuroendocrine actions of MERF, and the effect of the heptapeptide on the HPA system seems to be mediated by kappa-receptors. In the behavioral responses evoked by MERF, both CRH release and the action of the dopaminergic neurons of the subcortical motor system might be involved. MERF also appears to activate the paraventricular CRH neurons, but dopaminergic transmission does not seem to play a significant role in its hypothalamic action.
Insights
Met(5)-enkephalin-Arg(6)-Phe(7) (MERF) activates the hypothalamo-pituitary-adrenal (HPA) system and influences behavior in mice. Opioid and kappa-receptors mediate these neuroendocrine and behavioral effects, with corticotropin-releasing hormone (CRH) involvement.
Area of Science:
- Neuroendocrinology
- Behavioral Neuroscience
- Opioid Peptides
Background:
- Proenkephalin derivatives like Met(5)-enkephalin-Arg(6)-Phe(7) (MERF) are implicated in regulating physiological and behavioral processes.
- The hypothalamo-pituitary-adrenal (HPA) axis is a key neuroendocrine system involved in stress response and behavior.
- Understanding the receptor mechanisms underlying MERF's actions is crucial for elucidating its neurobiological roles.
Purpose of the Study:
- To investigate the effects of MERF on the HPA system and open-field behavior in mice.
- To identify the specific opioid and other receptor systems mediating MERF's neuroendocrine and behavioral actions.
- To explore the role of corticotropin-releasing hormone (CRH) and dopaminergic pathways in MERF's effects.
Main Methods:
- Intracerebroventricular (ICV) injection of MERF in mice.
- Administration of opioid antagonists (naloxone, nor-binaltorphimine) and dopamine/CRH antagonists prior to MERF.
- Measurement of plasma corticosterone levels.
- Assessment of open-field behavior (square crossing, rearing).
- In vitro superfusion of striatal slices to measure dopamine release.
Main Results:
- ICV injection of MERF increased locomotor activity, rearing, and plasma corticosterone levels.
- Both naloxone and nor-binaltorphimine dose-dependently attenuated MERF-induced HPA activation.
- Naloxone blocked MERF's behavioral effects, while nor-binaltorphimine showed no significant inhibition.
- CRH antagonist diminished both HPA activation and motor responses; haloperidol only affected motor activity.
- MERF did not alter basal or evoked dopamine release from striatal slices.
Conclusions:
- Opioid receptor mediation is predominant in MERF's neuroendocrine effects.
- MERF's action on the HPA system appears to be mediated by kappa-receptors.
- MERF-evoked behavioral responses involve CRH release and dopaminergic neurons.
- MERF activates paraventricular CRH neurons, but dopaminergic transmission is not critical for its hypothalamic action.
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