Abstract
Rationale
The fatty acid amide oleoyl glycine (OlGly) and its more stable methylated form oleoyl alanine (OlAla) reduce naloxone-precipitated morphine withdrawal (MWD)-induced conditioned gaping (nausea) responses in rats. In addition, OlGly has been shown to reduce lithium chloride (LiCl)–induced conditioned gaping in rats and vomiting in Suncus murinus (house musk shrews).
Objectives
Here, we compared the potential of these fatty acid amides to maintain their anti-nausea/anti-emetic effect over a delay. The following experiments examined the potential of a wider dose range of OlGly and OlAla to interfere with (1) LiCl-induced conditioned gaping in rats and (2) LiCl-induced vomiting in shrews, when administered 20 or 70 min prior to illness.
Results
OlAla (1, 5, 20 mg/kg) reduced LiCl-induced conditioned gaping, with OlGly only effective at the high dose (20 mg/kg), with no effect of pretreatment delay time. At the high dose of 20 mg/kg, OlGly increased passive drips during conditioning suggesting a sedative effect. In shrews, both OlGly and OlAla (1, 5 mg/kg) suppressed LiCl-induced vomiting, with no effect of pretreatment delay. OlAla more effectively suppressed vomiting, with OlAla (5 mg/kg) also increasing the latency to the first vomiting reaction.
Conclusions
OlAla was more effective than OlGly in reducing both LiCl-induced gaping in rats and LiCl-induced vomiting in shrews. These findings provide further evidence that these fatty acid amides may be useful treatments for nausea and vomiting, with OlAla demonstrating superior efficacy.
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Abbreviations
- ANOVA:
-
Analysis of variance
- CB1 :
-
Cannabinoid 1
- CPA:
-
Conditioned place aversion
- CPP:
-
Conditioned place preference
- F:
-
Female
- FAAH:
-
Fatty acid amide hydrolase
- ip:
-
Intraperitoneal
- LiCl:
-
Lithium chloride
- M:
-
Male
- MWD:
-
Morphine withdrawal
- OlAla:
-
Oleoyl alanine
- OlGly:
-
Oleoyl glycine
- PPARα:
-
Peroxisome proliferator-activated receptor alpha
- sem:
-
Standard error of the mean
- TR:
-
Taste reactivity
- VEH:
-
Vehicle
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Funding
The research described here was funded by research grants from the Natural Sciences and Engineering Council of Canada (NSERC: 03629) and Canadian Institutes of Health Research (CIHR: 388239).
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Rock, E.M., Limebeer, C.L., Smoum, R. et al. Effect of oleoyl glycine and oleoyl alanine on lithium chloride induced nausea in rats and vomiting in shrews. Psychopharmacology 239, 377–383 (2022). https://doi.org/10.1007/s00213-021-06005-4
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DOI: https://doi.org/10.1007/s00213-021-06005-4