Single Injection Of Artificial Synthetic Cannabinoids Reduce The Rat Vta Dopaminergic Neuronal Excitability

Cannabinoids are used for relieving pain, sedation and reducing diarrhea has been a long time, but continued use of such drugs makes addiction which difficult to withdrawal. From now on, there is no effective treatment, mainly because the specific mechanism of this addiction do not yet know. Sensitization of reward system is one of the mechanisms of drug addiction. As a key part of reward system the Ventral tegmental area is the origin of mesocorticolimbic dopamine system and have extensive contact whith the prefrontal cortex, nucleus accumbens, amygdala, hippocampus. The experiment shows that the effect of sensitization produced at VTA. Now the opion that drug addiction is accompanied by changes in synaptic plasticity has been widely recognized. Ungless et al found that a single injection of cocaine induced behavioral sensitization and the generation of LTP effect in the VTA dopaminergic neurons, while NMDA receptor antagonist can block the LTP effect and behavioral sensitization, suggesting that the synaptic plasticity of VTA dopaminergic neurons plays an important role in drug addiction. Five kinds of addictive drugs, amphetamines, cocaine, morphine, alcohol and nicotine can induced LTP effect in the VTA dopaminergic neurons. Recently, experiments showed that chronic cannabinoid injection facilitated the LTD effect in the VTA dopaminergic neurons induced by low frequency stimulation. The neuron circle is constitute by neurons and the synaptic connections between neurons, and the changes in synaptic plasticity and neuronal excitability will affect the properties of the entire circle. In cultured hippocampal neurons, correlated pre- and postsynaptic activity that induces long-term potentiation/long-term depression can aslo induce a presistent enhancement/reduction in the excitability of the presynaptic neuron. This is evident by a change of threshole forspike initiation and the mean ISI of presynaptic firing in response to a depolarizing input. The experiment aslo find that the expression of LTD was unaffected by treatments whith PKA inhibitors that had eliminated the reduction of presynaptic excitability.Similar separation of the enhancement of presynaptic excitability and LTP was also observed in another test. The bidirectional changes in the neuronal excitability and synaptic efficacy exhibit two distinct aspects of activity-induced modification of neural circuit. Previous studies of the role VTA dopaminergic neurons play in drug addiction focused on synaptic plasticity, while much less attention has been given to the changes of intrinsic excitability of neurons. With the purpose of observe the changes of excitability in dopaminergic neurons under the cannabinoid, the present study recorded the activity of VTA dopaminergic neurons in the appearance of picrotoxin, CNQX, AP-5 in rat brain slices using patch clamp technique. The study provides a new idea for the latter studies of the mechanisms of cannabinoid addiction.The results are as followings:l.when given step stimulation(0-300pA,1000ms) to VTA dopaminergic neurons, the firing threshold of dopamine cell after cannabinoid increased.The threshold is defined as the minimal injection current intensity of the first spike.2.The mean firing frequency of dopaminergic neuron decreased after cannabinoid when analysed spike numbers on ever step stimulation.3.The rest potential of dopaminergic neurons increased after the cannabinoid. The results indicated that single HU210 exposure decreases the intrinsic excitability in ventral tegmental area dopaminergic neurons.