Novel GPR18 Ligands in Rodent Pharmacological Tests: Effects on Mood, Pain, and Eating Disorders.
Małgorzata Frankowska, Karolina Wydra, Agata Suder, Magdalena Zaniewska, Dawid Gawliński, Joanna Miszkiel, Anna Furgała-Wojas, Kinga Sałat, Malgorzata Filip, Christa E. Müller, Katarzyna Kieć-Kononowicz, Magdalena Kotańska
International Journal of Molecular Sciences May 20, 2023 DOI: 10.3390/ijms24109046 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Male mice and rats |
| Interventions | PSB-KK-1415 PSB-CB-5 PSB-CB-27 Δ9-tetrahydrocannabinol (THC) |
| Topics | Anxiety Depression |
| Keywords | Gpr18 ligands Food intake Locomotor activity Pain Rodents Temperature δ9-THC-Vehicle Discrimination |
| Key points | The authors report that activating GPR18 with the agonist PSB-KK-1415 produced effects partly similar to cannabinoid receptor activation, affecting emotional behavior, food intake, and pain. They propose that GPR18 may be a therapeutic target for mood, pain, and/or eating disorders, while noting that further investigation is needed to clarify its function. |
Abstract
The lack of selective pharmacological tools has limited the full unraveling of G protein-coupled receptor 18 (GPR18) functions. The present study was aimed at discovering the activities of three novel preferential or selective GPR18 ligands, one agonist (PSB-KK-1415) and two antagonists (PSB-CB-5 and PSB-CB-27). We investigated these ligands in several screening tests, considering the relationship between GPR18 and the cannabinoid (CB) receptor system, and the control of endoCB signaling over emotions, food intake, pain sensation, and thermoregulation. We also assessed whether the novel compounds could modulate the subjective effects evoked by Δ9-tetrahydrocannabinol (THC). Male mice or rats were pretreated with the GPR18 ligands, and locomotor activity, depression- and anxiety-like symptoms, pain threshold, core temperature, food intake, and THC-vehicle discrimination were measured. Our screening analyses indicated that GPR18 activation partly results in effects that are similar to those of CB receptor activation, considering the impact on emotional behavior, food intake, and pain activity. Thus, the orphan GPR18 may provide a novel therapeutic target for mood, pain, and/or eating disorders, and further investigation is warranted to better discern its function.
Comparable studies
Other preclinical and animal studies on anxiety, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Chronic, Intermittent Microdoses of the Psychedelic N , N -Dimethyltryptamine (DMT) Produce Positive Effects on Mood and Anxiety in Rodents Male rats | 2019 | Animal study | |
| 3,4-Methylenedioxymethamphetamine facilitates fear extinction learning Mice | 2015 | Preclinical experimental study | |
| Repeated lysergic acid diethylamide (LSD) reverses stress-induced anxiety-like behavior, cortical synaptogenesis deficits and serotonergic neurotransmission decline Male mice exposed to chronic restraint stress | 2022 | Preclinical experimental study |
Citations in the library
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- Antidepressant-like effect of delta9-tetrahydrocannabinol and other cannabinoids isolated from Cannabis sativa L. Pharmacology, Biochemistry, and Behavior June 2010
- Cannabis: discrimination of "internal bliss"? Pharmacology, Biochemistry, and Behavior October 1999