Presynaptic adenosine A2A receptors control cannabinoid CB1 receptor mediated inhibition of striatal glutamatergic neurotransmission
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1
Universidade de Coimbra, Centro de Neurociencias e Biologia Celular, Portugal
Changing the strength of synaptic connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. Long-term changes at excitatory corticostriatal synapses are critically involved in e.g. motor control and learning or habit formation. Δ9- tetrahydrocannabinol (a CB1 cannabinoid receptor agonist) and caffeine (an adenosine A2A receptor antagonist) are widely used psychoactive substances affecting striatal synaptic plasticity. These two receptors were recently found to form heteromers in heterologous expression systems but little is known about the functional interaction between CB1 and A2A receptors in the basal ganglia. Since both receptors control striatal glutamatergic transmission we now probed the putative interaction between presynaptic CB1 and A2A receptors in the striatum. In extracellular field potentials recording, A2A receptor activation abrogated the CB1 receptor-mediated long-lasting depression of the field potential amplitude and the increase in paired-pulse facilitation, indicating a presynaptic site of interaction in the striatal circuitry. Immunocytochemical analysis showed that A2A receptors preferentially co-localize with CB1 receptors in a subset of striatal glutamatergic nerve terminals. In isolated striatal nerve terminals, A2A receptor activation inhibited whereas A2A receptor blockade facilitated the CB1R-mediated inhibition of depolarization-induced Ca2+ entry and glutamate release. Hence, this is the first report on presynaptic interaction between the adenosinergic and cannabinergic neuromodulatory systems. This mechanism may prompt testing the putative beneficial synergism that may arise from co-administration of A2A and CB1 receptor ligands in neuropsychiatric disorders affecting the basal ganglia.
Conference:
11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009.
Presentation Type:
Poster Presentation
Topic:
Neuronal Communication
Citation:
Ferreira
SG,
Martire
A,
Teresa-Tebano
M,
Chiodi
V,
Mackie
K,
Cunha
RA,
Popoli
P and
Kofalvi
A
(2009). Presynaptic adenosine A2A receptors control cannabinoid CB1 receptor mediated inhibition of striatal glutamatergic neurotransmission.
Front. Neurosci.
Conference Abstract:
11th Meeting of the Portuguese Society for Neuroscience.
doi: 10.3389/conf.neuro.01.2009.11.130
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Received:
11 Aug 2009;
Published Online:
11 Aug 2009.
*
Correspondence:
Samira G Ferreira, Universidade de Coimbra, Centro de Neurociencias e Biologia Celular, Alicante, Portugal, carsamira@gmail.com