Elsevier

Neuroscience

Volume 109, Issue 3, 14 February 2002, Pages 451-460
Neuroscience

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

https://doi.org/10.1016/S0306-4522(01)00509-7Get rights and content

Abstract

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.

Section snippets

Animals and tissue preparation

Animals were housed in a temperature- and humidity-controlled room with a 12 h light-dark cycle (light from 07:00–19:00) and with access to food and water ad libitum. The experimental protocols were approved by the Ethical Committee on Animal Care and Use of the Government of Bavaria, Germany.

Adult mice (3–5 months old; C57BL/6) were killed by cervical dislocation. Brains were removed, snap-frozen on dry-ice and stored at -80°C prior to sectioning. Brains were mounted on Tissue Tek

CB1 and D1 receptors

The highest levels of D1 transcripts are observed in the basal ganglia (Mansour et al., 1991, Weiner et al., 1991), including caudate putamen, nucleus accumbens, and olfactory tubercle. High levels of low-CB1-expressing cells are detected in the dorsolateral caudate putamen, while the nucleus accumbens contains only few low-CB1-expressing cells. The olfactory tubercle shows an intense staining due to a high density of low-CB1-expressing cells. Coexpressing cells were counted at a single-cell

Discussion

Increasing evidence indicates that a single receptor subtype may be linked to the formation of multiple, intracellular signals. However, it is unlikely that all signals driven by a single receptor subtype are equally operative under all circumstances, but it seems that the functional weight of one pathway relative to another can be altered by interactions with other receptors. The first indication for possible interactions between different receptors is given, when both receptors are expressed

Acknowledgements

We would like to thank Christine Schleicher for technical assistance, Dr. Thomas Lemberger (DKFZ, Heidelberg, Germany) for the D1 probe used for in situ hybridization experiments, Drs. Walter Sierralta and Gregor Eichele (MPI of Experimental Endocrinology, Hannover, Germany) for the experimental in situ hybridization protocol and Dr. Daniela Vogt-Weisenhorn for critical reading of the manuscript and valuable comments. This work was in part supported by a Grant from Deutsche

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