Respiratory depression and analgesia by opioid drugs in freely behaving larval zebrafish
- Keenan Research Centre for Biomedical Sciences. St. Michael’s Hospital Unity Health Toronto, Canada
- Department of Medicine, Faculty of Medicine, University of Toronto, Canada
Figures
Figure 1
Respiratory network activity quantified using mandible movements in freely-moving larval zebrafish.
(A) The brainstem respiratory network of the larval zebrafish produces respiratory mandible movements. (B) Respiratory mandible movements are used as an index of respiratory network activity. (C) …
Figure 2
Respiratory rate depression by the opioid analgesic fentanyl in larval zebrafish.
(A) Representative mandible movements in larvae exposed to embryo medium or a solution of fentanyl (1 µM). The rate of mandible movements was significantly decreased by fentanyl. (B) Larvae were …
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Figure 2—source data 1
Respiratory rate depression by the opioid analgesic fentanyl.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig2-data1-v2.xlsx
Figure 3
Opioid receptor pharmacology regulating respiratory depression in larval zebrafish.
(A) Representative tracings of mandible movements in larval zebrafish showing fentanyl (1 µM) reducing respiratory rate and reversal by the MOR antagonist naloxone (20 µM). (B) Fentanyl (1 µM) …
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Figure 3—source data 1
Opioid receptor pharmacology regulating respiratory depression.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig3-data1-v2.xlsx
Figure 4
Respiratory depression and respiratory stimulants in larval zebrafish.
(A) The respiratory stimulant BIMU8 (10 µM), a 5-HT4A serotonin receptor agonist, in combination with fentanyl (n = 20) was compared to fentanyl alone (n = 4) or BIMU8 alone (n = 21). BIMU8 was not …
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Figure 4—source data 1
Respiratory depression and respiratory stimulants.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig4-data1-v2.xlsx
Figure 5 with 1 supplement
Nociception by formalin and analgesia by fentanyl in larval zebrafish.
(A) As an index of nociception in larval zebrafish, we measured behavioral responses to the nociceptive stimulus formalin. We quantified swimming velocity in freely-moving larvae. Swimming velocity …
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Figure 5—source data 1
Nociception by formalin and analgesia by fentanyl.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig5-data1-v2.xlsx
Figure 5—figure supplement 1
Angular velocity in response to formalin and opioid drugs.
(A) Angular velocity is calculated as the number of degrees by unit of time. (B) Formalin reduced angular velocity (n = 21, p=0.011) compared to controls (n = 22), an effect not reversed by fentanyl …
Figure 6 with 1 supplement
Nociception by AITC and analgesia by fentanyl in larval zebrafish.
(A) As an index of nociception in larval zebrafish, we measured behavioral responses to the nociceptive stimulus AITC. We quantified swimming in freely-moving larvae. Swimming velocity was higher in …
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Figure 6—source data 1
Nociception by AITC and analgesia by fentanyl.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig6-data1-v2.xlsx
Figure 6—figure supplement 1
Angular velocity in response to AITC and opioid drugs.
AITC fish (n = 26) presented a lower angular velocity compared to controls (n = 25, p=0.002), an effect reversed in fentanyl/AITC group (n = 16, p=0.001). This effect was blocked by naloxone at 20 …
Figure 7 with 1 supplement
Analgesic profiles of larval zebrafish.
(A) To determine whether the analgesia assay can be replicated with non-opioid analgesics, we used lidocaine, an analgesic widely used in the clinic. Lidocaine with formalin (n = 19) only moderately …
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Figure 7—source data 1
Analgesic profiles of larval zebrafish.
- https://cdn.elifesciences.org/articles/63407/elife-63407-fig7-data1-v2.xlsx
Figure 7—figure supplement 1
Angular velocity in response to formalin, lidocaine, and stimulants.
(A) Formalin reduced angular velocity when compared to DMSO (n = 16, all p>0.05), an effect not reversed by lidocaine. (B) BIMU8 (n = 17) and CX614 (n = 12) had no effects on fentanyl/formalin …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers | Additional information |
|---|---|---|---|---|
| Strain, strain background (Danio rerio) | AB Zebrafish | Hospital for Sick Children and the University of Toronto Mississauga (ON, Canada) | ||
| Strain, strain background (Danio rerio) | Tübingen (TU) Zebrafish | Hospital for Sick Children and the University of Toronto Mississauga (ON, Canada) | ||
| Strain, strain background | AB, TU cross zebrafish | Crossed at St. Michael’s Hospital (ON, Canada) | ||
| Chemical compound, drug | Fentanyl citrate | Sandoz (QC, Canada) | Cat. No. 2520 | |
| Chemical compound, drug | Morphine sulfate | Sandoz (QC, Canada) | Cat. No. 5642 | |
| Chemical compound, drug | Naloxone hydrochloride | Omega (QC, Canada) | Cat. No. L0010224 | |
| Chemical compound, drug | CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) | Tocris (ON, Canada) | Cat. No. 1560/1 | |
| Chemical compound, drug | Lidocaine | Tocris (ON, Canada) | Cat. No. 3057 | |
| Chemical compound, drug | CX 614 | Tocris (ON, Canada) | Cat. No. 5149 | |
| Chemical compound, drug | BIMU 8 | Tocris (ON, Canada) | Cat. No. 4374/5 | |
| Chemical compound, drug | Allyl isothiocyanate (AITC) | Sigma-Aldrich (ON, Canada) | Cat. No. 36682 | |
| Chemical compound, drug | Formalin | VWR | Cat. No. 89370/094 | |
| Chemical compound, drug | Dimethyl sulfoxide (DMSO) | Sigma-Aldrich (ON, Canada) | Cat. No. 472301 | |
| Software, algorithm | Sigmaplot | Version 14, SAS | ||
| Software, algorithm | Adobe Illustrator | Creative Suite 5, Adobe | ||
| Software, algorithm | EthoVision XT | v15, Noldus Information Technology, Netherlands | ||
| Software, algorithm | Matlab | Mathworks, US |
