Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats

The underlying mechanism of dependence and rewarding effects of morphine is imperative to understand. The primary aim of this study was to investigate whether ropinirole D2/3 agonist affects the rewarding and reinforcing properties of morphine-induced conditioned place preference (CPP) and withdrawa...

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Main Authors: Andleeb Shahzadi, Oruc Yunusoglu, Enes Karabulut, Haktan Sonmez, Zeliha Yazici
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-06-01
Series:Frontiers in Behavioral Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2022.855241/full
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author Andleeb Shahzadi
Oruc Yunusoglu
Oruc Yunusoglu
Enes Karabulut
Enes Karabulut
Haktan Sonmez
Zeliha Yazici
Zeliha Yazici
author_facet Andleeb Shahzadi
Oruc Yunusoglu
Oruc Yunusoglu
Enes Karabulut
Enes Karabulut
Haktan Sonmez
Zeliha Yazici
Zeliha Yazici
author_sort Andleeb Shahzadi
collection DOAJ
description The underlying mechanism of dependence and rewarding effects of morphine is imperative to understand. The primary aim of this study was to investigate whether ropinirole D2/3 agonist affects the rewarding and reinforcing properties of morphine-induced conditioned place preference (CPP) and withdrawal syndromes in rats. On day one, the animals were randomly divided to conduct the pre-test. The morphine (10 mg/kg, i.p.) and/or saline was administered on alternate days in an 8-day CPP session. On day 10, 15 min prior to the post-conditioning test (expression), a single dose of ropinirole (1, 2, and 5 mg/kg, i.p.) was given to rats. In extinction session, ropinirole was injected daily, and CPP was extinguished by repeated testing, with intervals of 3 days. Finally, reinstatement was assessed by administering ropinirole (1, 2, and 5 mg/kg) 15 min before the morphine injection. Morphine dependence was developed by administering increasing doses of morphine (10–50 mg/kg, i.p.). To assess withdrawal symptoms, ropinirole (1, 2, and 5 mg/kg) was injected 15 min before naloxone (2 mg/kg, s.c.) administration. The present study confirms that ropinirole attenuates expression and reinstatement of CPP, while it precipitates the extinction of morphine-induced CPP. Naloxone-precipitated morphine withdrawal symptoms, including wet dog shakes and weight loss, were attenuated although jumping was increased by a single ropinirole injection. Thus, ropinirole was influential in attenuating expression, reducing drug seeking and weakening reinstatement via the dopaminergic system. These findings show that ropinirole might affect neuro-adaptive changes related to dependence.
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spelling doaj.art-9a9e0f09f80e488180a1b3f2f9d6ea002022-12-22T00:31:43ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532022-06-011610.3389/fnbeh.2022.855241855241Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in RatsAndleeb Shahzadi0Oruc Yunusoglu1Oruc Yunusoglu2Enes Karabulut3Enes Karabulut4Haktan Sonmez5Zeliha Yazici6Zeliha Yazici7Department of Medical Pharmacology, Faculty of Medicine-Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine-Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Bolu Abant Izzet Baysal University, Bolu, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine-Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, TurkeyMehmet Akif Ersoy Thoracic and Cardiovascular Surgery Training and Research Hospital, Istanbul, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine-Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine-Cerrahpasa, Istanbul University-Cerrahpasa, Istanbul, TurkeyDepartment of Medical Pharmacology, Faculty of Medicine, Biruni University, Istanbul, TurkeyThe underlying mechanism of dependence and rewarding effects of morphine is imperative to understand. The primary aim of this study was to investigate whether ropinirole D2/3 agonist affects the rewarding and reinforcing properties of morphine-induced conditioned place preference (CPP) and withdrawal syndromes in rats. On day one, the animals were randomly divided to conduct the pre-test. The morphine (10 mg/kg, i.p.) and/or saline was administered on alternate days in an 8-day CPP session. On day 10, 15 min prior to the post-conditioning test (expression), a single dose of ropinirole (1, 2, and 5 mg/kg, i.p.) was given to rats. In extinction session, ropinirole was injected daily, and CPP was extinguished by repeated testing, with intervals of 3 days. Finally, reinstatement was assessed by administering ropinirole (1, 2, and 5 mg/kg) 15 min before the morphine injection. Morphine dependence was developed by administering increasing doses of morphine (10–50 mg/kg, i.p.). To assess withdrawal symptoms, ropinirole (1, 2, and 5 mg/kg) was injected 15 min before naloxone (2 mg/kg, s.c.) administration. The present study confirms that ropinirole attenuates expression and reinstatement of CPP, while it precipitates the extinction of morphine-induced CPP. Naloxone-precipitated morphine withdrawal symptoms, including wet dog shakes and weight loss, were attenuated although jumping was increased by a single ropinirole injection. Thus, ropinirole was influential in attenuating expression, reducing drug seeking and weakening reinstatement via the dopaminergic system. These findings show that ropinirole might affect neuro-adaptive changes related to dependence.https://www.frontiersin.org/articles/10.3389/fnbeh.2022.855241/fullmorphineconditioned place preferenceropinirolewithdrawal syndromeexpressionreinstatement
spellingShingle Andleeb Shahzadi
Oruc Yunusoglu
Oruc Yunusoglu
Enes Karabulut
Enes Karabulut
Haktan Sonmez
Zeliha Yazici
Zeliha Yazici
Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
Frontiers in Behavioral Neuroscience
morphine
conditioned place preference
ropinirole
withdrawal syndrome
expression
reinstatement
title Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
title_full Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
title_fullStr Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
title_full_unstemmed Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
title_short Influence of Selective Dopamine Agonist Ropinirole on Conditioned Place Preference and Somatic Signs of Morphine Withdrawal in Rats
title_sort influence of selective dopamine agonist ropinirole on conditioned place preference and somatic signs of morphine withdrawal in rats
topic morphine
conditioned place preference
ropinirole
withdrawal syndrome
expression
reinstatement
url https://www.frontiersin.org/articles/10.3389/fnbeh.2022.855241/full
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