Interactions between mGluRs and NMDA receptors underlie LTD in the nucleus accumbens

FERNANDO KASANETZ; PV PIAZZA; OLIVIER MANZONI

Amsterdam

Congreso; 7th FENS Forum of Neuroscience; 2010

FENS

The nucleusaccumbens (NAC) is a central component of the meso-cortico-limbic system thatplays a prominent role in motivation and reward. Synaptic plasticity in the NAC,by remodeling neural circuits, is believed to be important for the processing ofstimulus-reward associations. Alterations ofsynaptic transmission and plasticity in the NAC have been related to severalpsychiatric diseases, including drug addiction. Although it is largely knownthat drugs of abuse induce numerous modifications in brain function, a directassociation between the loose of control over drug intake that characterizeaddiction and synaptic plasticity was only recently reported. Thus, we observedthat cocaine addiction was associated with a persistent impairment in aspecific form of long term depression (LTD) in the NAC. A clear understandingof the molecular substrates mediating this metaplasticity could unravel newtargets for the development of efficient therapies of drug abuse. To gaininsight into this, we studied the molecular mechanisms involved in theexpression of LTD in the NAC by means of whole cell patch clamp recording inbrain slices obtained from adult rats. LTD was induced by pairing presynapticstimulation and postsynaptic depolarization (p-LTD). We addressed the synapticreceptors required and observed that p-LTD was blocked by antagonist of NMDA(AP5: 0.1mM) and metabotropic glutamate receptors group 1/5 (MPEP: 10 microM;CPCCOet: 50 microM). We ruled out the involvement CB1 receptors, as theantagonist AM-251 (4 microM) did not interfere with p-LTD.Our data showsthat the interaction between NMDA and metabotropic glutamate receptors plays arole in p-LTD. Understanding the nature of this may be important for the studyof drug addiction.