Elsevier

Life Sciences

Volume 62, Issue 2, 5 December 1997, Pages 103-114
Life Sciences

ARE BOMBESIN-LIKE PEPTIDES INVOLVED IN THE MEDIATION OF STRESS RESPONSE?

https://doi.org/10.1016/S0024-3205(97)01057-6Get rights and content

Abstract

The neurochemical mechanisms underlying the coincident activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system in response to stress remain unclear. Central injection of the neuropeptide bombesin (BN) potently stimulates the release of epinephrine from the adrenal medulla, adrenocorticotropic hormone (ACTH) from the pituitary gland, and elicits behaviors typically associated with increased emotionality and arousal. The current studies assessed whether stress is associated with 1) fluctuations in the endogenous regional levels of BN-like peptides and/or 2) changes in BN receptor density. Male Sprague-Dawley rats received either no treatment or were subjected to acute immobilization stress for 10, 30 or 120 min. Plasma ACTH levels increased in response to stress, peaking at 30 min. BN-like immunoreactivity increased significantly at the hypothalamus and medulla, within 30 min; however with more sustained immobilization (120 min) BN-like immunoreactivity declined to control levels. Levels of BN-like peptides remained unchanged in several other regions, including the hippocampus, striatum, midbrain, pituitary, and pons. Autoradiographic analysis revealed that the density of BN receptor varied in a regionally specific manner. Significant stress related increases in binding were found at the nucleus of the solitary tract (at 30 and 120 min), and at the paraventricular (at 120 min) and arcuate nuclei (at 120 min) of the hypothalamus. These data indicate the BN-like peptides may play a role in the mediation and/or modulation of response to stress.

Section snippets

Material and Methods

Animals. Male Sprague Dawley rats (weighing between 300 and 350 g), obtained from Charles River (St-Constant, Quebec) were used in both experiments. All rats were individually housed and maintained on a 12 h light/dark cycle (with lights on at 6:00 a.m.), with ambient temperature of 23°C and a relative humidity of about 60%. All animals had free access to food (Purina rat chow) and water. Experiments were run in a separate room between 09:00 and 11:00 a.m.

Experiment 1. Rats were randomly

Results

Experiment 1. The ANOVA revealed that BN-like immunoreactivity varied as a function of the interaction between Brain region and Stress duration (F18,165 =2.15; P<0.0069). Tukey's post hoc comparisons revealed that the interaction was attributable to a differential regional responsiveness to the stressor application. In accordance with previously published data, individual brain regions differed significantly in their bombesin-like immunoreactivity, with the highest concentration being detected

Discussion

The objective of the present study was to determine whether the endogenous BN/GRP peptidergic system was involved in the mediation of some of the effects of acute stress. These results demonstrated that acute immobilization stress induced site-specific changes in the endogenous levels of BN-like peptide as well as in BN/GRP receptor density. To our knowledge this is the first account of stress-induced alterations in the BN/GRP system in the brain, and provides evidence supporting the role of

Acknowledgements

This work was supported by a grant from the Natural Sciences and Engineering Research Council of Canada (NSERC) to Z.M. and an MRC studentship to P.K.

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