Pre-synaptic adenosine A2A receptors control cannabinoid CB1 receptor-mediated inhibition of striatal glutamatergic neurotransmission.
An interaction between adenosine A(2A) receptors (A(2A) Rs) and cannabinoid CB(1) receptors (CB(1) Rs) has been consistently reported to occur in the striatum, although the precise mechanisms are not completely understood. As both receptors control striatal glutamatergic transmission, we now probed the putative interaction between pre-synaptic CB(1) R and A(2A) R in the striatum. In extracellular field potentials recordings in corticostriatal slices from Wistar rats, A(2A) R activation by CGS21680 inhibited CB(1) R-mediated effects (depression of synaptic response and increase in paired-pulse facilitation). Moreover, in superfused rat striatal nerve terminals, A(2A) R activation prevented, while A(2A) R inhibition facilitated, the CB(1) R-mediated inhibition of 4-aminopyridine-evoked glutamate release. In summary, the present study provides converging neurochemical and electrophysiological support for the occurrence of a tight control of CB(1) R function by A(2A) Rs in glutamatergic terminals of the striatum. In view of the key role of glutamate to trigger the recruitment of striatal circuits, this pre-synaptic interaction between CB(1) R and A(2A) R may be of relevance for the pathogenesis and the treatment of neuropsychiatric disorders affecting the basal ganglia.
Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Alberto
A
Martire
Maria Teresa
MT
Tebano
Valentina
V
Chiodi
Samira G
SG
Ferreira
Rodrigo A
RA
Cunha
Attila
A
Köfalvi
Patrizia
P
Popoli
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D043705:Receptor, Adenosine A2A; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid