Presynaptic α2-adrenoceptor modulates glutamatergic synaptic transmission in rat nucleus accumbens in vitro.

The nucleus accumbens (NAc), integrating information from the prefrontal cortex and limbic structures, plays a critical role in reward and emotion regulation. Previous studies have reported that the NAc shell receives direct noradrenergic projections, and activation of α2-adrenoceptor (α2-AR) in the NAc shell decreases the fear or anxiety level of rats. However, the underlying mechanism is still little known. Intriguingly, glutamatergic neurotransmission in the NAc shell is closely related to reward and emotion. Here, using brain slice preparations and whole-cell patch clamp recordings, we examined the effect of activation of α2-AR on glutamatergic neurotransmission in the NAc shell. Perfusing slice with α2-AR selective agonist clonidine (CLON) reduced the evoked excitatory postsynaptic currents (EPSCs) on the NAc shell neurons. This inhibitory effect on AMPA-mediated glutamatergic EPSCs was blocked by the α2-AR selective antagonist yohimbine (YOH). Notably, CLON reduced the frequency but not the amplitude of miniature EPSCs. Furthermore, CLON decreased the first EPSC amplitude but increased the paired-pulse facilitation on the NAc shell neurons, and it did not affect postsynaptic AMPA/NMDA ratio, revealing a presynaptic mechanism of α2-AR-mediated inhibition on glutamatergic transmission. In addition, the modulation on glutamatergic transmission by α2-AR was independent of presynaptic NMDA receptor. These results suggest that noradrenergic afferent inputs may suppress glutamatergic synaptic transmission via presynaptic α2-AR in the NAc shell, and actively participate in rewarding and emotional processes via the NAc.