Cannabinoid CB1 receptor and serotonin 3 receptor subunit A (5‐HT_3A) are co‐expressed in GABA neurons in the rat telencephalon

Abstract

Among all described serotonin (5-HT) receptors in mammals, the type three (5-HT3) is the only ligand-gated ion channel receptor for serotonin. By using double in situ hybridization histochemistry, we found co-expression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor in neurons of the rat telencephalon. Double-labeled 5-HT3A/CB1 neurons were found in the anterior olfactory nucleus, superficial and deep layers of the cortex, hippocampal formation (hippocampus, dentate gyrus, subiculum, and entorhinal cortex) and amygdala. Analysis of the proportion of neurons co-expressing 5-HT3A and CB1 receptors in the cortex and amygdala showed that, depending on the brain region, 37-53% of all neurons expressing the 5-HT3A subunit also expressed CB1 transcripts; 16-72% of the total population of neurons expressing CB1 mRNA co-expressed the 5-HT3A subunit. By using a combination of double in situ hybridization and immunohistochemistry, we demonstrated that 5-HT3A/CB1-expressing neurons contained the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These results imply that in distinct regions of the telencephalon, GABA neurons that react to cannabinoids may also be responsive to serotonin through 5-HT3 receptors. Cellular coexistence of 5-HT3A and CB1 transcripts in interneurons of the cortex, hippocampal formation, and amygdala suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission in brain areas involved in cognition, memory, and emotion.

Hippocampal interneurons co-express transcripts encoding the α7 nicotinic receptor subunit and the cannabinoid receptor 1

“…These neurons in their vast majority co-express CB1 mRNA (Hermann et al, 2002;Morales and Backman, 2002;Morales et al, 2004). Considering that most of the interneurons expressing α7 nACh mRNA co-express CB1 mRNA, we conclude that the majority of these neurons also contain transcripts encoding the 5-HT 3A subunit and the neuropeptide CCK.…”

“…Moreover, these α7 nACh/CB1 expressing neurons constitute the main subpopulation of GABAergic neurons within the detected population of CB1 containing interneurons in the hippocampus and DG. Marsicano and Lutz, 1999;Morales and Backman, 2002;Morales et al, 2004). Thus, we used a combination of in situ hybridization (for detection of α7 nACh mRNA) and immunohistochemistry (for detection of CCK) to investigate the degree of overlapping of the cell populations expressing α7 nACh mRNA or CCK immunoreactivity (Fig.…”

“…These CB1 interneurons contain cholecystokinin (CCK) (Katona et al, 1999;Marsicano and Lutz, 1999;Tsou et al, 1999) and co-express the subunit A of the 5-HT 3 R (Hermann et al, 2002;Morales and Backman, 2002;Morales et al, 2004). The CB1 receptor is a G-protein-coupled receptor that mediates the effects of the major psychoactive constituent of marijuana, delta 9-tetrahydrocannabinol (Δ 9-THC; Howlett, 1995).…”

Endocannabinoid-Mediated Control of Synaptic Transmission

“…(108,133). CB 1 and 5-HT 3A were reported to be coexpressed with CB 1 in CCK-containing GABAergic neurons of the cerebral cortex, hippocampus, and amygdala (360). Since 5-HT 3 activation facilitates GABA release, serotonin and endocannabinoids could interact with each other at the molecular or circuit level for regulation of GABA release.…”

From Phytocannabinoids to Cannabinoid Receptors and Endocannabinoids: Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology

“…⌬ 9 -THC inhibits 5-HT 3 receptors, whose activation appears to play a dominant role in acute emesis (930). CB1 and 5-HT 3 receptors colocalize on GABAergic neurons with opposite effects on GABA release (586). Interestingly, ⌬…”