Opioid-like adverse effects of tianeptine in male rats and mice View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-02-24

AUTHORS

T. R. Baird, H. I. Akbarali, W. L. Dewey, H. Elder, M. Kang, S. A. Marsh, M. R. Peace, J. L. Poklis, E. J. Santos, S. S. Negus

ABSTRACT

RationaleTianeptine is a mu-opioid receptor (MOR) agonist with increasing reports of abuse in human populations. Preclinical data regarding the abuse potential and other opioid-like adverse effects of tianeptine at supratherapeutic doses are sparse.ObjectivesThe present study evaluated tianeptine in a rat model of abuse potential assessment and in mouse models of motor, gastrointestinal, and respiratory adverse effects.MethodsAbuse potential was assessed in adult male Sprague–Dawley rats using an intracranial self-stimulation (ICSS) procedure to determine effects of acute and repeated tianeptine on responding for electrical brain stimulation. Male ICR mice were used to determine the effects of tianeptine in assays of locomotor behavior and gastrointestinal motility. Male Swiss-Webster mice were monitored for respiratory changes using whole-body plethysmography.ResultsIn rats, acute tianeptine produced weak and delayed evidence for abuse-related ICSS facilitation at an intermediate dose (10 mg/kg, IP) and pronounced, naltrexone-preventable ICSS depression at a higher dose (32 mg/kg, IP). Repeated 7-day tianeptine (10 and 32 mg/kg/day, IP) produced no increase in abuse-related ICSS facilitation, only modest tolerance to ICSS depression, and no evidence of physical dependence. In mice, tianeptine produced dose-dependent, naltrexone-preventable locomotor activation. Tianeptine (100 mg/kg, SC) also significantly inhibited gastrointestinal motility and produced naloxone-reversible respiratory depression.ConclusionsTianeptine presents as a MOR agonist with resistance to tolerance and dependence in our ICSS assay in rats, and it has lower abuse potential by this metric than many commonly abused opioids. Nonetheless, tianeptine produces MOR agonist-like acute adverse effects that include motor impairment, constipation, and respiratory depression. More... »

PAGES

2187-2199

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00213-022-06093-w

DOI

http://dx.doi.org/10.1007/s00213-022-06093-w

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35211768


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34 ICSS
35 ICSS depression
36 ICSS facilitation
37 MOR agonists
38 ObjectivesThe present study
39 ResultsIn rats
40 Sprague-Dawley rats
41 Swiss Webster mice
42 abuse
43 abuse potential
44 abuse potential assessment
45 abuse-related ICSS facilitation
46 activation
47 acute adverse effects
48 adult male Sprague-Dawley rats
49 adverse effects
50 agonists
51 assays
52 assessment
53 behavior
54 brain stimulation
55 changes
56 constipation
57 data
58 dependence
59 depression
60 dose
61 doses
62 effect
63 effects of tianeptine
64 electrical brain stimulation
65 evidence
66 facilitation
67 gastrointestinal motility
68 high dose
69 human population
70 impairment
71 increase
72 intermediate dose
73 intracranial self-stimulation (ICSS) procedure
74 locomotor activation
75 locomotor behavior
76 low abuse potential
77 male ICR mice
78 male Sprague-Dawley rats
79 male Swiss Webster mice
80 male rats
81 metrics
82 mice
83 model
84 modest tolerance
85 motility
86 motor
87 motor impairment
88 mouse model
89 mu-opioid receptor agonist
90 opioids
91 physical dependence
92 plethysmography
93 population
94 potential
95 potential assessment
96 preclinical data
97 present study
98 procedure
99 rat model
100 rats
101 receptor agonist
102 report
103 reports of abuse
104 resistance
105 respiratory adverse effects
106 respiratory changes
107 respiratory depression
108 self-stimulation procedure
109 stimulation
110 study
111 supratherapeutic doses
112 tianeptine
113 tolerance
114 whole-body plethysmography
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