Rat Cocaine Self-administration Model Of The Establishment And Administration Of The Program On The Desirability,

Currently, drug abuse has overruned all over the world, giving rise to more and more serious social and medical issues, researchers have pay attention to study the mechanism of it. Drug use caused addiction, which generally starts with recreational use and deteriorates into a compulsive and chronically-relapsing drug taking disorder over time. It can and should be understood through a coordinated analysis of brain function and behavior. Drug self-administration, one of reliable methods for evaluating the psychic dependence liability of drug, have recently employed fixed and progressive ratio schedules to examine the neural substrates of drug reinforcement. The great majority of self-administration use simple fixed ratio (FR) schedule of reinforcement, which is useful for exploring patterns of rate of drug intake. The progressive ratio (PR) schedule can quantify the reinforcing effects of drugs through the quantitative estimate of breakpoint and to determine their reinforcing efficacy.Our study aimed at establishing the drug self-administration and discussing the factors which may affect the process of establishmen. Self-administration requires implantation of indwelling jugular catheters through which drugs are injected to blood. On the successful establishment of FR1 cocaine self-administration model in rats, we discussed the impact of pre-sucrose training and observed changes of craving for drugs by increasing FR and the effect of different cocaine dose. After building a stable self-administration behavior in FR1 and FR5, we emplyed Koob program for progressive ratio schedule and the breakpoint was found, while using step 3 and 7 training before, further training Koob program and modified Koob program, the breakpoint didn't appear, then discussing the reasons of these results. After creating a stable model of cocaine self-administration with the emergence of a breakpoint, we discussed the influence of A2-peptide on the cocaine self-administration. The major results were described as follows:1. Implantation of indwelling jugular catheters was essential in establishing the self-administration model. The model was limited only by relatively loss of catheter patency and blood clotting. Infection or inflammation may also result in the relatively quick loss of catheter patency.2. Our study has successfully established FR1 cocaine self-administration model in rats. After 11 days of self-administration training, the number of cocaine (0.75mg/kg/inj.) injection in 2 hours was steady between 18-24 times and there was a significant difference of active nosepokers in cocaine group and the saline group. The unactive nosepokers in cocaine group was drop, while there was no change during the whole experiment in saline group.3. Whether food pre-training or not, it did't not affect the successful building of cocaine self-administration model, but it can speed up the rate and stabilize self-administration model.4. FR and drug dose can influence the self-administration model.when FR increased, there were sharply increasement of the active nospokers and relatively stable of injection, indicating that FR schedule can reflecte to some extent drug craving animals; in a certain dose range, the lower doses of cocaine, the larger number of active nose pokers and drug injection, and vice versa.5. The breakpoint appropriate depended on how the PR schedule was implemented. The results for progressive ratio of Koob program were that the number of drug injection was 20-25 times, but the number of active nosepokers was increased to 500-700, then breakpoint was observed in the third day. However, after early training for program of step 3 and 7 and then Koob program, the breakpoint have not seen; followed by two amendment procedure of Koob training, the results were still, indicating that the breakpoint was not easy to measured in the animals which have been simple trained. The reasons why the breakpoint was not observed maybe that early process of easy training make animals not to produce a sense of disappointment. At the same time, long-term injection of cocaine produced a compulsive drug seeking behavior which drive animal to get the drugs by ceaselessly touching nosepoker.6. A2-peptide had no effect on the cocaine rewarding.