title: Adenosine-cannabinoid receptor interactions. Implications for striatal function.
abstract: Adenosine and endocannabinoids are very ubiquitous non-classical neurotransmitters that exert a modulatory role on the transmission of other more 'classical' neurotransmitters. In this review we will focus on their common role as modulators of dopamine and glutamate neurotransmission in the striatum, the main input structure of the basal ganglia. We will pay particular attention to the role of adenosine A(2A) receptors and cannabinoid CB(1) receptors. Experimental results suggest that presynaptic CB(1) receptors interacting with A(2A) receptors in cortico-striatal glutamatergic terminals that make synaptic contact with dynorphinergic medium-sized spiny neurons (MSNs) are involved in the motor-depressant and addictive effects of cannabinoids. On the other hand, postsynaptic CB(1) receptors interacting with A(2A) and D(2) receptors in the dendritic spines of enkephalinergic MSNs and postsynaptic CB(1) receptors in the dendritic spines of dynorphinergic MSN are probably involved in the cataleptogenic effects of cannabinoids. These receptor interactions most probably depend on the existence of a variety of heteromers of A(2A), CB(1) and D(2) receptors in different elements of striatal spine modules. Drugs selective for the different striatal A(2A) and CB(1) receptor heteromers could be used for the treatment of neuropsychiatric disorders and drug addiction and they could provide effective drugs with fewer side effects than currently used drugs.
authors.affiliation: National Institute on Drug Abuse, IRP, NIH, DHHS, Baltimore, MD 21224, USA. sferre@intra.nida.nih.gov
authors.forename: Sergi
authors.initials: S
authors.lastname: Ferré
authors.forename: Carme
authors.initials: C
authors.lastname: Lluís
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Justinova
authors.forename: César
authors.initials: C
authors.lastname: Quiroz
authors.forename: Marco
authors.initials: M
authors.lastname: Orru
authors.forename: Gemma
authors.initials: G
authors.lastname: Navarro
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
authors.forename: Steven R
authors.initials: SR
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D002375:Catalepsy / Q000503:physiopathology; D003342:Corpus Striatum / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D055503:Protein Multimerization; D020239:Receptor Cross-Talk / Q000502:physiology*; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D019966:Substance-Related Disorders / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D043705:Receptor, Adenosine A2A; D043884:Receptor, Cannabinoid, CB1