Preclinical evidence for the use of the atypical antipsychotic, brexpiprazole, for opioid use disorder

被引:5
作者
Nickols, Julia E. R. [1 ]
Dursun, Serdar M. [2 ,3 ]
Taylor, Anna M. W. [1 ,3 ,4 ]
机构
[1] Univ Alberta, Dept Pharmacol, 8613 114 Street NW, MSB 9-47, Edmonton, AB T6G 2R3, Canada
[2] Univ Alberta, Dept Psychiat, Edmonton, AB, Canada
[3] Univ Alberta, Neurosci & Mental Hlth Inst, Edmonton, AB, Canada
[4] Univ Alberta, Dept Anesthesiol & Pain Med, Edmonton, AB, Canada
关键词
DRUG-INDUCED REINSTATEMENT; INCENTIVE-SENSITIZATION; LOCOMOTOR SENSITIZATION; INDUCED HYPERALGESIA; MORPHINE; ARIPIPRAZOLE; EXPRESSION; RECEPTOR; SYSTEM; OPIATE;
D O I
10.1016/j.neuropharm.2023.109546
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Opioid addiction is characterized by adaptations in the mesolimbic dopamine system that occur during chronic opioid use. Alterations in dopaminergic transmission contribute to pathological drug-seeking behavior and other symptoms associated with opioid withdrawal following drug discontinuation, making drug abstinence challenging and contributing to high rates of relapse among those suffering from substance use disorder. Recently, the use of dopamine partial agonists has been proposed as a potential strategy to restore dopaminergic signalling during drug withdrawal, while avoiding the adverse side effects associated with stronger modulators of dopaminergic transmission. We investigated the effects of the atypical antipsychotic brexpiprazole, which is a partial agonist at dopamine D2 and D3 receptors, in a mouse model of opioid dependence. The development of opioid dependence in mice is characterized by locomotor sensitization, analgesic tolerance, opioid-induced hyperalgesia, and drug-seeking behavior. We set up four paradigms to model the effects of brexpiprazole on each of these adaptations that occur during chronic opioid use in male and female C57BL/6J mice. Concomitant treatment of brexpiprazole during chronic morphine administration attenuated the development of locomotor sensitization. Brexpiprazole treatment abolished morphine place preference and blocked reinstatement of this behavior following extinction. Brexpiprazole treatment did not alter morphine analgesia, nor did it impact the development of morphine tolerance. However, brexpiprazole treatment did prevent the expression of opioid-induced hyperalgesia in a tail-withdrawal assay, while failing to improve somatic withdrawal symptoms. Altogether, these results provide preclinical evidence for the efficacy of brexpiprazole as a modulator of dopamine-dependent behaviors during opioid use and withdrawal.
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页数:9
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共 54 条
[1]   The antipsychotic aripiprazole selectively prevents the stimulant and rewarding effects of morphine in mice [J].
Almeida-Santos, Ana F. ;
Gobira, Pedro H. ;
Souza, Diego P. ;
Ferreira, Renata C. M. ;
Romero, Thiago R. ;
Duarte, Igor D. ;
Aguiar, Daniele C. ;
Moreira, Fabricio A. .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2014, 742 :139-144
[2]  
Amada Naoki, 2019, Neuropsychopharmacology Reports, V39, P279, DOI 10.1002/npr2.12076
[3]   The debate over dopamine's role in reward: the case for incentive salience [J].
Berridge, Kent C. .
PSYCHOPHARMACOLOGY, 2007, 191 (03) :391-431
[4]   Divergent behavioral responses in protracted opioid withdrawal in male and female C57BL/6J mice [J].
Bravo, Isabel M. ;
Luster, Brennon R. ;
Flanigan, Meghan E. ;
Perez, Patric J. ;
Cogan, Elizabeth S. ;
Schmidt, Karl T. ;
McElligott, Zoe A. .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2020, 51 (03) :742-754
[5]   Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation [J].
Cahill, Catherine M. ;
Walwyn, Wendy ;
Taylor, Anna M. W. ;
Pradhan, Amynah A. A. ;
Evans, Christopher J. .
TRENDS IN PHARMACOLOGICAL SCIENCES, 2016, 37 (11) :963-976
[6]   Opioid-induced hyperalgesia in humans - Molecular mechanisms and clinical considerations [J].
Chu, Larry F. ;
Angst, Martin S. ;
Clark, David .
CLINICAL JOURNAL OF PAIN, 2008, 24 (06) :479-496
[7]   Long-Acting Injectable Antipsychotic Treatment in Schizophrenia and Co-occurring Substance Use Disorders: A Systematic Review [J].
Coles, Alexandria S. ;
Knezevic, Dunja ;
George, Tony P. ;
Correll, Christoph U. ;
Kane, John M. ;
Castle, David .
FRONTIERS IN PSYCHIATRY, 2021, 12
[8]   Morphine-induced analgesic tolerance, locomotor sensitization and physical dependence do not require modification of mu opioid receptor, cdk5 and adenylate cyclase activity [J].
Contet, Candice ;
Filliol, Dorninique ;
Matifas, Audrey ;
Kieffer, Brigitte L. .
NEUROPHARMACOLOGY, 2008, 54 (03) :475-486
[9]   Brexpiprazole: so far so good [J].
Das, Saibal ;
Barnwal, Preeti ;
Winston, Blessed A. ;
Mondal, Somnath ;
Saha, Indranil .
THERAPEUTIC ADVANCES IN PSYCHOPHARMACOLOGY, 2016, 6 (01) :39-54
[10]   Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization [J].
De Vries, TJ ;
Schoffelmeer, ANM ;
Binnekade, R ;
Murder, AH ;
Vanderschuren, LJMJ .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1998, 10 (11) :3565-3571