do birds have cannabinoid receptors

Two cannabinoid receptors, CB1 and CB2, are expressed in mammals, birds, reptiles, and fish. The presence of cannabinoid receptors in invertebrates has been controversial, due to conflicting evidence. We conducted a systematic review of the literature, using expanded search parameters. Evidence presented in the literature varied in validity, ranging from crude in vivo behavioural assays to robust in silico ortholog discovery. No research existed for several clades of invertebrates; we therefore tested for cannabinoid receptors in seven representative species, using tritiated ligand binding assays with [3H]CP55,940 displaced by the CB1-selective antagonist SR141716A. Specific binding of [3H]CP55,940 was found in neural membranes of Ciona intestinalis (Deuterstoma, a positive control), Lumbricusterrestris (Lophotrochozoa), and three ecdysozoans: Peripatoides novae-zealandiae (Onychophora), Jasus edwardi (Crustacea) and Panagrellus redivivus (Nematoda); the potency of displacement by SR141716A was comparable to measurements on rat cerebellum. No specific binding was observed in Actinothoe albocincta (Cnidaria) or Tethya aurantium (Porifera). The phylogenetic distribution of cannabinoid receptors may address taxonomic questions; previous studies suggested that the loss of CB1 was a synapomorphy shared by ecdysozoans. Our discovery of cannabinoid receptors in some nematodes, onychophorans, and crustaceans does not contradict the Ecdysozoa hypothesis, but gives it no support. We hypothesize that cannabinoid receptors evolved in the last common ancestor of bilaterians, with secondary loss occurring in insects and other clades. Conflicting data regarding Cnidarians precludes hypotheses regarding the last common ancestor of eumetazoans. No cannabinoid receptors are expressed in sponges, which probably diverged before the origin of the eumetazoan ancestor.

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To verify these transcriptomic patterns indicating functional effects of CNR2 loss on neuroimmune functioning in parrots, we followed the CNR1/2, IL1B and IL6 expression on messenger RNA (mRNA) level across the two taxa using RT-qPCR. In the budgerigar (E1), relative IL1B and IL6 expression increased in the brain following the LPS stimulation (p < 0.001 for both markers; electronic supplementary material, S1, tables S11–S13). By contrast, the expression of CNR1 was independent of the LPS treatment (p > 0.05; electronic supplementary material, S1, tables S11 and S14). Considering the putative interspecific differences, we next compared changes in IL1B and CNR1 gene expression on the mRNA levels following LPS stimulation in the six parrot species (E2). The results confirmed that the expression of IL1B in the brain changes in response to LPS stimulation, regardless of species (p = 0.005; electronic supplementary material, S1, tables S11 and S15). Again, we found no effect of the LPS stimulation on CNR1 mRNA expression (p > 0.050; electronic supplementary material, S1, tables S11 and S16). By contrast, in the zebra finch, a species with a functional CNR2 receptor, there was no significant effect of the LPS treatment on expression changes of any of these genes (p > 0.050; electronic supplementary material, S1, tables S11, S17–S20). There was no correlation between CNR1 and IL1B (p > 0.050) or IL6 (p > 0.050) expression in brain in any of the compared taxa (electronic supplementary material, S1, figures S3–S7). However, expression of CNR2 in zebra finch was significantly positively correlated with expression of IL1B (p = 0.009; r = 0.711; electronic supplementary material, S1, figure S8), but not IL6 (p = 0.753, r = 0.315, electronic supplementary material, S1, figure S9). Taken altogether, these results confirm no overall increase in expression of neuroinflammatory markers in the CNR2-intact passerines following LPS stimulation, but a contrasting significant upregulation of these markers in the brains of LPS-stimulated CNR2-deficient parrots (figure 4a,b). Figure 4.

Figure 4. Expression of (a) IL1B and (b) IL6 following peripheral stimulation with LPS in the brains of budgerigars and zebra finches. Gene expression assessed based on RT-qPCR is shown as centred standardized relative expression (logQst) values, i.e. species population average is equal to 0. C = controls, LPS = LPS-stimulated treatments. Statistically significant differences (p ≪ 0.001; electronic supplementary material, table S11 in SM1) are marked with asterisks. (Online version in colour.)

The statistical analysis was performed in Rstudio v. 2021. 09. 0 [71]. Using a Wilcoxon paired test, the first transcriptomic cytokine expression data were examined for variations in the expression of inflammatory genes between budgerigars and zebra finches. The results were then plotted in a heatmap created with the pheatmap package. Next, the RT-qPCR verification of these results was performed. Using decadic logarithms (logQst), the Qst values were normalized due to their non-Gaussian distribution. Gene expression (continuous) was used as the response variable in the linear models (LMs) in the “Ime4” package to evaluate the effects of experimental treatment on changes in gene expression. The complete model included treatment, sex, and time as explanatory variables for the Budgerigar (E1) dataset. Treatment, sex, and species were all included in the full model as explanatory variables for the comparative parrot (E2) dataset. The only explanatory variable included in the full model for the zebra finch (E3) dataset, based on the E1 results, was treatment. Models deemed minimum adequate are those in which every term is significant at p ≤ 0. 05) were chosen by removing non-significant terms from the complete models in reverse order. Using F-statistics, changes in deviance with corresponding changes in degrees of freedom (ANOVA) and the Akaike information criterion validated each step of the models’ backward elimination process. The association between the expression of the CNR genes and IL1B and IL6 was examined using the Pearson correlation test.

Based on our comparative genomic search, which revealed that parrots only consistently overlook the CNR2 gene among negative regulators of inflammation, here we map the putative CNR2 loss events across vertebrate phylogeny using genomic and transcriptomic data. We then reconstruct the CNR2 loss events in parrots using examples from the genomes of kakapo (Strigops habroptila) and budgerigar (Melopsittacus undulatus). We look for compensatory adaptations in CNR1 in species lacking CNR2 using positive selection analysis. Lastly, we evaluate the effects of CNR2 loss on neuroimmune regulation in parrots by contrasting the expression patterns of neuroinflammation markers in the brain during an immune response in parrots and passerines.

Therefore, our findings imply that CNR2 loss in parrots may affect regulation that reduces systemic proinflammatory signaling (such as that mediated by IL1B and IL6). Our interpretation is supported by evidence from CNR2-knock-out mice that exhibit pronounced immunopathology [88]. Therefore, our findings support the notion that the absence of CNR2 has regulatory significance in sensitivity to neuroinflammation and raise the possibility that parrots may be more susceptible to neurological syndromes.

Globally, the incidence of neurodegenerative and psychiatric disorders in people has increased [1,2]. Remarkably, comparable psychological disorders—also known as behavioral disorders in animals—have been identified on a regular basis in certain animals with advanced cognitive abilities, such as parrots [3-5]. Veterinarians see and diagnose symptoms such as anxiety, apathy, overeating, indifference, and self-damage (plucking feathers) in parrots, just as they do in humans [6–8]. Although the exact causes of behavioral disorders in parrots are currently unknown, neural inflammation has recently been connected to them in humans [9]. Signals from the periphery, where pathogens and tissue damage stimulate pattern recognition receptors to trigger immune responses, can cause brain neuroinflammation [10]. The activation of brain microglia and astrocytes [11] and subsequent cytokine signaling may modify central nervous system functioning by interfering with normal brain neuronal regulation [12,13]. Key indicators of neuroinflammation, proinflammatory cytokines like interleukin 1 beta (IL1B) or 6 (IL6) [14,15] become overexpressed in the brain [16, 17]. A well-balanced regulation of the neuroimmune interaction is necessary for mental health. It has been demonstrated that cannabinoids recognizable by cannabinoid receptors (CNRs) are among the neuronal modulators connecting the immune and nervous systems and have significant anti-neuroinflammatory effects in humans [18–21]. Animal immunological factors influencing behavioral disorders are far less understood than in humans, and interspecific variation in the neuroimmune regulatory networks is still unclear. Given their advanced cognitive capacities [22], extensive neural networks [23], and prevalence of psychopathologies [6, 7], parrots may be able to shed light on the general principles underlying how neuroinflammation affects behavior.

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Do animals have cannabinoid receptors?

This suggests that they serve an important and basic function in animal physiology. In general, cannabinoid receptor molecules are similar among different species. Thus, cannabinoid receptors likely fill many similar functions in a broad range of animals, including humans.

Do ducks have cannabinoid receptors?

Two cannabinoid receptors, CB1 and CB2, are expressed in mammals, birds, reptiles, and fish.

Do any insects have cannabinoid receptors?

Cannabinoid receptors are absent in insects.

Where are cannabinoids found in nature?

Cannabinoids (/kəˈnæbənɔɪdzˌ ˈkænəbənɔɪdz/) are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds.