Functional interactions between mu opioid and cannabinoid CB1 receptors in the nucleus accumbens.

OLIVIER LASALLE; MARJA SEPPERS; FERNANDO KASANETZ; MARSICANO G, MANZONI O, KIEFFER BL

Amsterdam

Congreso; 7th FENS Forum of Neuroscience; 2010

FENS

Interactionsbetween the opioid and cannabinoid systems have been suggested bymorphology, biochemistry and behaviour. Agonists at both the µopioid receptor and the CB1 receptor inhibit excitatory synaptictransmission in the nucleus accumbens. Our study examined theirinteraction using electrophysiological methods in rat brain slices.Since both receptor types are subject to desensitisation afterrepeated exposure to agonist, homologous and heterologousdesensitisation were tested. We found that chronic in vivo exposureto a CB agonist, WIN 55, 212-2, desensitises both CB1 and µreceptors. Chronic in vivo exposure to morphine, however, has notbeen tested in relation to CB1. This interaction was alsoinvestigated at the level of endocannabinoid dependent synapticplasticity. In brain slices prepared from rats chronically treatedwith the CB agonist, there was a marked reduction ofendocannabinoid-mediated long-term depression (LTD). We thereforetested the impact of chronic morphine on LTD. Finally, the inhibitoryeffects of sequentially applied µ agonist DAMGO and CP on evoked andminiature excitatory postsynaptic currents (EPSC) were measured. Wealso evaluated cross-talk between the two receptors usingpharmacological and genetic (CB1R and µ receptor null mice) tools.The complex interactions between cannabinoids and opioids that werediscovered, are not only relevant to the pathological state ofaddiction, but underline receptor cooperation in normal synapticphysiology.