Neuropharmacology

Biography

Biography: Costanza Burattini

Abstract

The nucleus accumbens (NAc), a ventromedial component of the mesocorticolimbic dopamine system, plays a pivotal role in the mediation of motivation and reward, drug addiction, learning, feeding and mood disorders. This brain area receives dopaminergic inputs from the ventral tegmental area, glutamatergic afferents from cortical and sub cortical limbic structures and a dense serotonergic innervation from dorsal raphe nucleus neurons. Glutamatergic synapses within the NAc can express plasticity, including endocannabinoid (eCB)-long-term depression (LTD); eCBs are arachidonic acid-derived lipid signaling molecules acting at CB receptors. Anatomical studies have shown that CB1 receptors are located presynaptically on glutamatergic neurons in the NAc, and that they participate in the regulation of transmitter release. Recent evidences demonstrate an extensive co-localization of CB1 and 5-HT receptors within the NAc suggesting the potential for interplay between them. In the present study, performed in a rat slice preparation containing the NAc, we found that prolonged (20 min) low-frequency (4 Hz) stimulation (LFS-4Hz) of glutamatergic afferences induces a novel form of eCB-LTD in the NAc core, which requires 5-HT2 and CB1 receptors activation and L-type voltage-gated Ca2+ channels (VGCC) opening. Present results suggest that LFS-4Hz induces the release of 5-HT, increases Ca2+ influx through VGCC and e-CB production and release; the eCB travels retrogradely and binds to presynaptic CB1 receptors, causing a long-lasting decrease of glutamate release resulting in LTD. These observations might be helpful to understand the neurophysiological mechanisms underlying drug addiction, major depression and other psychiatric disorders characterized by dysfunction of 5-HT neurotransmission in the NAc.