TITLE:
Low-dose morphine elicits ventilatory excitant and depressant responses in conscious rats: Role of peripheral µ-opioid receptors
AUTHORS:
Fraser Henderson Jr., Walter J. May, Ryan B. Gruber, Alex P. Young, Lisa A. Palmer, Benjamin Gaston, Stephen J. Lewis
KEYWORDS:
Morphine; Minute Ventilation; Tolerance; Peripheral and Central Opioid Receptors; Conscious Rats
JOURNAL NAME:
Open Journal of Molecular and Integrative Physiology,
Vol.3 No.3,
August
28,
2013
ABSTRACT: The
systemic administration of morphine affects ventilation via a mixture of
central and peripheral actions. The aims of this study were to characterize
the ventilatory responses elicited by a low dose of morphine in conscious
rats; to determine whether tolerance develops to these responses; and to determine
the potential roles of peripheral μ-opioid
receptors (μ-ORs) in these responses.
Ventilatory parameters were monitored via unrestrained whole-body plethysmography.
Conscious male Sprague-Dawley rats received an intravenous injection of
vehicle or the peripherally-restricted μ-OR
antagonist, naloxone methiodide (NLXmi), and then three successive injections
of morphine (1 mg/kg) given 30 min apart. The first injection of morphine in
vehicle-treated rats elicited an array of ventilatory excitant (i.e., increases in frequency of breathing,
minute volume, respiratory drive, peak inspiratory and expiratory flows, accompanied by decreases in inspiratory time and end inspiratory pause) and
inhibitory (i.e., a decrease in tidal
volume and an increase in expiratory time) responses. Subsequent injections
of morphine elicited progressively and substantially smaller responses. The
pattern of ventilatory responses elicited by the first injection of morphine
was substantially affected by pretreatment with NLXmi whereas NLXmi minimally
affected the development of tolerance to these responses. Low-dose morphine
elicits an array of ventilatory excitant and depressant effects in conscious
rats that are subject to the development of tolerance. Many of these initial actions of morphine appear to
involve activation of peripheral μ-ORs
whereas the development of tolerance to these responses does not.