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Role of Vagus Nerve Stimulation on Heroin-seeking Behavior Induced by Condition Cues in Rats

Author: YuJing
Tutor: LiuHuiFen
School: Ningbo University
Course: Biochemistry and Molecular Biology
Keywords: Vagus nerve stimulation Self-administration Drug-seeking behavior Locus coeruleus Alpha - 2A receptor
CLC: R749.6
Type: Master's thesis
Year: 2011
Downloads: 14
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Abstract


Purpose of vagus nerve stimulation (vagus nerve stimulation, VNS) has been widely used in the treatment of many neurological and psychiatric disorders, including epilepsy, depression, anxiety, obesity, Alzheimer's disease and other, but not much about vagus nerve stimulation in the treatment of drug addiction research reports. Our previous studies have found that VNS inhibits of heroin ignited and clues induced rats the recovery of self-administration, the purpose of the research projects in order to further clarify the acute and chronic VNS recovery rats administered heroin drug-seeking behavior impact, as well as the central sites and possible molecular biology mechanisms provide a theoretical basis for clinical heroin relapse prevention. Experiment, of acute VNS clues induced rat heroin drug-seeking behavior in Methods Rats surgery recovery 7 days after daily self-administration training 4h consecutive 14 days, to establish the FR1 procedures rat heroin self-administration model, 15d embedded VNS electrode postoperative recovery 3d, environment extinction training 10d clues induced drug-seeking behavior tests. The rats were randomly divided into a single vagus nerve stimulation group (acute VNS group) and sham-operated group (sham group) (n = 10). The acute VNS group in last subsided training given before stimulation (stimulation parameters: frequency 30Hz, pulse width 0.5ms, current 1mA, 30s on, 5min off consecutive 2h), and then immediately after the end of extinction training given after 24 hours of drug-seeking behavioral tests. Sham-operated group stimulation current of 0 mA, with the VNS group. Immediately after the results of self-administration of acute VNS stimulation in rats given drug-seeking behavior test, compared with the sham, the effective number of nose touch was significantly reduced (P = 0.001), no significant change (P = 0.696) number of invalid nose touch. Self-administration of acute VNS stimulation after 24 hours to give drug-seeking behavior test, compared to sham-operated the effective nose touch and invalid nose touch number had no significant difference (P = 0.188, P = 0.875). The second experiment, repeated VNS drug-seeking behavior the clues in rats induced by heroin and the Alpha-2AR expression of Methods Rats heroin self-administration model and VNS electrode embedded in the same experiment. The rats were randomly divided into chronic vagus nerve stimulation group (Chronic VNS group) and sham-operated control group (sham group) (n = 10). The chronic VNS group given once a day before the extinction training stimulation (stimulation parameters: frequency 30Hz, pulse width 0.5ms, current 1mA, 30s on, 5min off consecutive hours) of continuous stimulation to 10 days, and then the last subsided the end of the training immediately after or 24 hours after induction of clues heroin drug-seeking behavior tests. Sham-operated group stimulation current of 0 mA, with the VNS group. Behavioral tests immediately after the cerebral locus coeruleus (Locus coeruleus, LC) and prefrontal cortex (prefrontal cortex, PFC) area, Western-blot detection of norepinephrine Alpha-2A receptor expression. The results self-administration in rats after chronic VNS stimulation given to drug-seeking behavior immediately or 24 hours after the test, compared with the sham group, the effective number of nose touch were significantly reduced (P = 0.000, P = 0.000). Western-blot test results found that chronic VNS rats LC and PFC within the alpha-2A receptor expression than in the control group was significantly increased (P = 0.007, P = 0.002). Experiment three, cut off the left side of fans walking nerve VNS suppression clue-induced of heroin look for drug behavior affect the method of experimental processes with the experimental one, the animals were randomly divided into four groups (n = 5): sham surgery group (SHAM), cut does not stimulate group (cut ), the upper end of the stimulation group (Ascend) and the lower end of the stimulation group (descend). Heroin self-administration training is completed, the line of the left vagus nerve transection. Ascend group and descend group in extinction training every day give fans nerves upper or lower stimulation, stimulate 5d clues induced drug-seeking behavior test. Results Compared with the cut group, the the Ascend group and descend group can significantly reduce the effective number of nose touch (P = 0.000, P = 0.000), and Ascend group inhibition of drug seeking reaction was significantly stronger descend group (P = 0.012) ; and the effective number of nose contact between the cut group and the sham group was no significant difference (P = 0.293). Experiment, LC norepinephrine neuronal damage VNS suppression clue heroin-induced drug-seeking behavior intervention effect. The method of experimental processes with the experimental animals were randomly divided into four groups (n = 5): sham operation group (sham), DSP Group, VNS group, DSP VNS group. DSP group and DSP the VNS group of rats the VNS surgery 5 days before the intraperitoneal injection of toxin DSP-4 selective injury LC norepinephrine neurons. VNS group and DSP VNS group is also given once a day before the extinction training vagus nerve stimulation, continuous stimulation 10d clues heroin-induced drug-seeking behavior test. VNS group, compared with the DSP group, the number of effective nose touch a significant reduction (P = 0.000); DSP VNS group and the VNS group, a significant increase in the number of effective nose touch (P = 0.000); DSP VNS group and DSP group phase than, the effective number of nose touch no significant change (P = 0.124) Conclusion: This study found that acute or chronic VNS significantly inhibited conditions clues in rats induced by heroin drug-seeking behavior, and chronic VNS suppression seek clues heroin-induced The medicine acts of at least is sustainable 24h. 2 DSP injury LC noradrenergic systems significantly blocked the inhibitory effect of VNS drug-seeking behavior in rats, and heroin relapse after the treatment of rats with chronic VNS LC and PFC brain regions Alpha-2A receptor expression was significantly increased, suggesting that The LC noradrenergic systems involved in the VNS to suppress heroin relapse, and further found that alpha-2A receptor may mediate the role. 3 vagus nerve upstream and downstream loop are involved in the VNS suppression conditions clues induced rat the role of drug-seeking behavior, but mainly by the upstream solitary tract nucleus - locus coeruleus pathway play a role.

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