Single Cocaine Injection On Rat Vta Dopaminergic Neurons In Cell Excitability

Cocaine is a common addictive drug and it can induce and maintain a series of complex addictive effects. Mesolimbic dopamine system has a very close relationship with reward and drug addiction, and activation of the mesolimbic dopamine system is an important neurobiology foundation of drug addiction. Ventral tegmental area dopaminergic neurons project to the prefrontal cortex and nucleus accumbens, and then activating a large number of related brain areas, so that animals receive intense euphoria, then there is a strong desire for drug seeking. And with using addictive drugs, mesolimbic dopamine system can make adaptive changes accordingly, so that addiction is a very unusual learning and memory activity.Nervous system is a large and complex neural network interconnected by a large number of neurons. Over the years, people were most interested in studying synaptic transmission in long-term potentiation to explain the mechanism of drug addiction. It is the common cytological mechanism in learning and memory. Having given mice single cocaine exposure, Ungless found in vivo the VTA dopamine neurons appeared long-term potentiation. However, after single cocaine exposure, whether intrinsic plasticity in VTA dopaminergic neurons changed has not been reported.This experiment used whole-cell patch-clamping in midbrain slices, bathing with antagonist PTX, CNQX, AP-5, giving dopaminergic neurons a series of step current, to explore the intrinsic plasticity in VTA dopaminergic neurons after cocaine exposure.Main observed measures:1 Rate of spontaneous firing and resting membrane potential:Statistics in the ventral tegmental area dopaminergic neurons of the basic electrophysiological properties, compared with the saline group, cocaine group increased proportion of spontaneous, decreased resting membrane potential, statistics showed that the rate of spontaneous firing resting membrane potential had no significant difference between cocaine and saline groups.2 Input resistance:Compared input resistance, there were no significant difference between cocaine and saline groups.3 Rate of excitatory typeâ…¢:In the experiment there were typeâ…¢of excitatory neurons both in cocaine and saline groups, and the rate of typeâ…¢in cocaine groups less than the saline group, the statistics showed that the two groups was not significant differences.4 Firing range:By firing range in dopaminergic neurons to see the effect of single cocaine exposure on intrinsic plasticity. Cocaine group of dopaminergic neurons had low input current to evoked the action potential, and found that after single cocaine exposure the number of spiking in dopaminergic neurons increased.5 Rheobase:The results showed that rheobase of dopaminergic neurons in cocaine group was significant lower than the saline group, indicating that dopaminergic neurons in cocaine group was more exciting, more sensitive to external stimuli.6 Mean firing rate:Mean firing rate in cocaine group can reach lOHz, while the saline group only 7Hz. compared with saline group, after single cocaine exposure, dopaminergic neurons generated more action potentials.7 Instant frequency:Comparing instant frequency between the first spike and second spike of dopaminergic neurons in cocaine-treated animals and saline-treated ones, the results showed that cocaine group and the saline group of dopaminergic neurons in instant frequency increase with the injection current increases, and the instant frequency of cocaine group were higher than saline group.8 Spike latency:Giving dopaminergic neurons injected current, statistic the latency of the first action potential. The results showed that the latency of the first action potential was higher than saline group and there were no significant difference between the two groups. At 7 injected current the mean firing rate had significant difference, compared the latency at these injected current, showed no significant difference in cocaine and saline groups.The above results show that after single cocaine exposure increases the intrinsic excitability in ventral tegmental area dopaminergic neurons, suggesting that dopaminergic neurons excitability changes may also play a role in the process of addiction.