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Abstract

Efficient repetitive clinical use of morphine is limited by its numerous side effects, whereasanalgesic tolerance necessitates subsequent increases in morphine dose to achieve adequate levelsof analgesia. While many studies focused on analgesic tolerance, the effect of morphine dosing onnon-analgesic effects has been overlooked. This study aimed to characterize morphine-inducedbehavior and the development and progression of morphine-induced behavioral tolerance. Adultmale Sprague–Dawley rats were repetitively treated with subcutaneous morphine for 14 days in twodose groups (A: 5 mg/kg/day (b.i.d.) → 10 mg/kg/day; B: 10 mg/kg/day (b.i.d.) → 20 mg/kg/day).Motor behavior was assessed daily (distance traveled, speed, moving time, rearing, rotation) in anopen-field arena, before and 30 min post-injections. Antinociception was measured using tail-flickand hot-plate assays. All measured parameters were highly suppressed in both dosing groups onthe first treatment day, followed by a gradual manifestation of behavioral tolerance as the treatmentprogressed. Animals in the high-dose group showed increased locomotor activity after 10 days ofmorphine treatment. This excitatory phase converted to an inhibition of behavior when a highermorphine dose was introduced. We suggest that the excitatory locomotor effects of repetitive high dose morphine exposure represent a signature of its behavioral and antinociceptive tolerance.

Item Type:	Article
Authors/Creators:	Paul, AK and Gueven, N and Dietis, N
Keywords:	morphine dosing, behavior, locomotor activity, tolerance
Journal or Publication Title:	Molecules
Publisher:	Molecular Diversity Preservation International
ISSN:	1420-3049
DOI / ID Number:	10.3390/molecules26144355
Copyright Information:	Copyright 2021 by the authors.Licensee MDPI, Basel, Switzerland.This article is an open access articledistributed under the terms andconditions of the Creative CommonsAttribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Related URLs:	Google Scholar: Gueven, N UTAS Profile: Gueven, N
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