Differential impact of naltrexone on luteinizing hormone release during single versus repetitive exposure to restraint stress

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The objective of the present study was to determine the impact of repeated exposure to the same stressor on opiate receptor-mediated inhibition of basal and stress-related alterations of pituitary LH release. Groups of intact adult male rats were exposed to 8 hr of restraint stress for either 1 or 14 consecutive days. Animals in each group were injected intravenously with the specific opioid receptor antagonist naltrexone (NALT, 2 mg/kg bodyweight) or the vehicle saline (SAL) prior to the final scheduled stress episode. Rats pretreated with SAL prior to the single exposure to stress exhibited an increase in plasma LH over the 1st hr of stress, followed by a decline in hormone levels, which reached significance between 3 and 7 hr after initiation of the stress. NALT pretreatment of rats prior to restraint significantly blunted the suppressive effect of stress on circulating LH. Rats repeatedly exposed to stress did not show any significant alteration in plasma LH levels from prestress values at any time during their final stress episode. Pretreatment of chronically stressed rats with NALT before reexposure to stress resulted in plasma hormone levels that were not different from those in animals pretreated with SAL. When the opioid antagonist was administered to animals 24 hr after termination of single or multiple exposures to restraint, NALT-induced increases in basal plasma LH were significantly attenuated in the chronically stressed rats compared to animals subjected to stress only once or not at all. These results indicate that repeated daily exposure to restraint stress can result in the habituation of the hypothalamo-pituitary LH hormonal axis to the suppressive effects of this stress on hormone release. This study also suggests that multiple stress may promote a decline in the inhibitory tonus mediated by opioid receptors on hormone release during stress reexposure and may diminish opioid influence on basal LH release, at least within a 24-hr period following exposure to stress.