Coexistence of serotonin 3 (5‐HT₃) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus

Abstract

Using in situ hybridization histochemistry, a high degree of coexpression of the functional 5-HT3A subunit of the 5-HT3 receptor and the central CB1 cannabinoid receptor was detected in all subfields of the hippocampus and subgranular layer of the dentate gyrus (DG). Semi-quantitative analysis demonstrated that, depending on the hippocampal layer, 72-88% of CB1-expressing interneurons coexpress the 5-HT3A subunit. Within the DG, 5-HT3A/CB1 double-labeled neurons were confined to the subgranular layer, where close to 80% of all CB1-expressing basket neurons were found to contain 5-HT3A subunit transcripts. These results provide the first evidence indicating that the only ion channel receptor for serotonin and central CB1 cannabinoid receptor coexist in neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These findings suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission. However, activation of 5-HT3- or CB1-receptors are likely to have opposing regulatory effects on GABA neurotransmission, as 5-HT3 receptor activation by serotonin results in the release of GABA, while CB1 activation by cannabinoids results in inhibition of GABA release.

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.…”

“…In situ hybridization was performed as previously described (Morales and Backman, 2002). Cryosections were rinsed 3×10 min in diethyl pyrocarbonate (DEPC) -treated PB, incubated for 10 min in PB containing 0.5% Triton X-100, rinsed 3×10 min with DEPC-PB, treated with 0.2 M HCl for 15 min, rinsed 3×10 min with DEPC-PB, and then acetylated with 0.25% acetic anhydride in 0.1 M triethanolamine (pH 8.0) for 10 min.…”

“…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).…”

Serotonin as a Modulator of Glutamate- and GABA-Mediated Neurotransmission: Implications in Physiological Functions and in Pathology

“…Similarly to the hippocampus, modulation of GABA release from interneurons (mainly inhibition by 5-HT 1A receptors and stimulation by 5-HT 2 and/or 5-HT 3 receptors) has also been observed in other areas, among which dentate gyrus [132,152], enthorinal cortex [40,165], piriform cortex [115], frontal and anterior cingulate cortex [192].…”