Coexpression of the cannabinoid receptor type 1 with dopamine and serotonin receptors in distinct neuronal subpopulations of the adult mouse forebrain.

The cannabinoid receptor type 1 (CB1) displays unusual properties, including the dual capacity to inhibit or stimulate adenylate cyclase and a brain density considerably higher than the majority of G protein-coupled receptors. Together with overlapping expression patterns of dopamine and serotonin receptors this suggests a potential of CB1 to modulate the function of the dopamine and serotonin system. Indeed, pharmacological studies provide evidence for cross-talks between CB1 and receptors of these neurotransmitter systems. In trying to obtain further insights into possible functional and/or structural interactions between CB1 and the dopamine receptors and the serotonin receptors, we performed double-label in situ hybridization at the cellular level on mouse forebrain sections by combining a digoxigenin-labelled riboprobe for CB1 with 35S-labelled riboprobes for dopamine receptors D1 and D2, and for serotonin receptors 5-HT1B and 5-HT3, respectively. As a general rule, we found that CB1 colocalizes with D1, D2 and 5-HT1B only in low-CB1-expressing cells which are principal projecting neurons, whereas CB1 coexpression with 5-HT3 was also observed in high-CB1-expressing cells which are considered to be mostly GABAergic. In striatum and olfactory tubercle, CB1 is coexpressed to a high extent with D1, D2 and 5-HT1B. Throughout the hippocampal formation, CB1 is coexpressed with D2, 5-HT1B and 5-HT3. In the neocortex, coexpression was detected only with 5-HT1B and 5-HT3. In summary a distinct pattern is emerging for the cannabinoid system with regard to its colocalization with dopamine and serotonin receptors and, therefore, it is likely that different mechanisms underlie its cross-talk with these neurotransmitter systems.