Single Cocaine Injection Area Vta Da Neurons Of Rat Excitatory Synaptic Transmission And The Influence Of Inner Excitability

The mesocorticolimbic dopamine system has a very close relationship with reward and drug addiction. This system includes two main projection pathways of dopamine neurons in ventral tegmental area (VTA):one is projected from VTA to the nucleus of accumbens (Nac) and striatum, known as mesolimbic dopamine system, and the other is from VTA to the prefrontal cortex, known as mesocortical dopamine system. The two pathways are collectively known as mesocorticolimbic dopamine systems. Ample evidence support that the functional adaption of the mesolimbic dopamine system contributes to craving and relapseinduced by addictive drugs.Today cocaine is one of the world’s major addictive drugs and it can cause and maintain a series of addictive effects with very complex mechanisms. The study from Ungless et al. showed that a single injection of cocaine can make glutamate synaptic transmission on VTA dopamine (DA) present a long-term potentiation (LTP). However, whether injection of cocaine affects another key factor, DA neuron’s cell body excitability which determines the neuron output, remains unclear.To further study the impact of a single cocaine injection on rat VTA DA neurons excitatory synaptic transmission and intrinsic excitability, this work adopts vitro patch-clamp technique to study changes of spontaneous slow inward currents (SICs), the intrinsic excitability and EPSCs from VTA DA neurons24hours after a single cocaine injection. The main results are as follows:1. Excitatory synaptic transmission on DA neurons was enhanced24hours after a single cocaine injectionThrough blocking NMDAR by AP-5perfusion, AMPAR/NMDAR current ratio and NMDAR current decay time constant were calculated.,24hours after a single cocaine injection enhanced the AMPAR/NMDAR current ratio and prolonged NMDAR current decay time.2.24hours after a single cocaine injection enhanced intrinsic excitability of DA neuronsUnder the conditions that perfusing slices with PTX, AP-5and CNQX to block DA neuron’s excitatory and inhibitory synaptic inputs, respectively, DA neuron of cocaine group showed a lower rheobase current, mean firing rate, an increased discharge numbers and an enhanced average discharge frequency, compared with saline group.3.24hours after a single cocaine injection, extrasynaptic NMDA receptor currents of DA neuron were enhanced.Bathing slices with normal artificial cerebrospinal fluid,0Mg2+, Mg2+plus Ca2+artificial cerebrospinal fluid (ACSF), SIC frequency, amplitude and wave area of DA neuron from cocaine group was significantly greater than those from saline group.In conclusion,24hours after a single cocaine injection,, the VTA DA neuron’s excitatory synaptic transmission, the intrinsic excitability and extra synaptic NMDA receptor currents were significantly enhanced. Our study indicates synaptic transmission strength and intrinsic excitability after a single injection of cocaine can bring a synergistic effect, and extrasynaptic NMDA receptor activation may be one of key ways to mediate such synergies.