Using in situ hybridization histochemistry, a high degree of co-expression 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). Semiquantitative analysis demonstrated that, depending on the hippocampal layer, 72% to 88% of CB1 expressing interneurons co-express 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 g-amino butyric 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000449-01
Application #
6680294
Study Section
(CNRB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2002
Total Cost
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code