The Effects Of Neuroactive Peptide Urocortin2 On VTA Neuron’s Spontaneous Discharge And DA-ergic Neurotransmission In Morphine Addiction

Objective The study investigated the mechanism and inhibitory effects of neuro-active peptide, urocortin2(UCN2) on ventral tegmental area(VTA)nervous activity of morphine addiction rats, and provide drug target for drug addiction.Methods Morphine addiction rats and the seven-pipe microiontophoresis method were used to observe the effects of UCN2 on VTA neuron’s spontaneous discharge changing rule. As well as, the inhibitory effects of UCN2 on DA neuron’s cluster spontaneous discharge, identify UCN2 and DA on the same VTA neuron. Morever, the inhibitor of corticotropin-regulating factor’s receptor(CRF-2R) and the blocker of protein kinase A(PKA), AST-2B and H89, were used to investigate the effects of UCN2 on VTA neuron’s of morphine addiction rats.Results We observed 52 VTA neurons. In the experiment we found that UCN2 could inhibit the firing rate 82%(31/38) of the tested VTA neuron(P<0.01), the discharge frequency changed from 20.89±2.86 Hz to 13.66±3.93 Hz(P<0.01).Further, the inhibitor of PKA, AST-2B and H89 could ablolish the inhibitory effects of UCN2. In addition, UCN2 could inhibit the explosive discharge ofDA-ergic in vta, the firing rates were decreased from(25.57±1.64) Hz to(13.42±1.60) Hz(P<0.01). Morever, the excitatory firing of VTA neurons was attenuated by addition of UCN2, while AST application could inhibit the UCN2’s inhibitory effects.Conclusions1. The results proved that UCN2 could inhibit the DA-ergic firng rates in VTA on morphine addiction, UCN and DA on the same VTA neuron.2. The results suggested that UCN2 could regulate the effects of VTA via PKA pathway and might thereby contribute to the improvement of drug addiction.