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Self-Administration of Drugs. Fig. 3. A cumulative record illustrating the response pattern of a rat self-administering cocaine on a progressive ratio schedule. Upward movements of the record represent responses; downward angle ticks indicate a drug injection. The first response resulted in an injection. The response requirements for subsequent injections escalated through an exponential series. In this case, the animal self-administered 16 injections. The final ratio was 145.

Self-Administration of Drugs. Fig. 4. Graph shows the dose-response relationship in rats for a variety of drugs self-administered on a PR schedule. Groups of rats were first trained to self-administer cocaine. Various doses of test drug were then evaluated. The dependent measure was the final ratio (or breakpoint). HD24 is an experimental tropane compound synthesized by Dr. H. M. L. Davies. Note that the selected drugs have a range of reinforcing efficacies and potencies.

Figure 4 shows the dose-response curves for several different stimulant drugs. Higher unit doses are associated with higher breakpoints. The large range of breakpoints across various drugs suggests a wide spectrum of reinforcing efficacies.

Whether responding is measured while drug is on board is a critical theoretical issue. In some cases, it is imperative that drug seeking be measured in a drug-free state. However, it has become clear that blood levels of drug can greatly affect responding and in fact may be one of the most important factors which drives further drug taking once it has started. In this context, it is important to emphasize that the breakpoint on a PR schedule measures the motivation to continue a binge and not necessarily the motivation to start a binge.

In the past decade there has been a pronounced increase in the number of studies examining ''relapse'' to drug taking. In relapse experiments, animals are tested either in a drug-free state or under the influence of an experimenter delivered drug. Typically rats are trained to self-administer (e.g., cocaine or heroin) and in many cases, responding is then extinguished. The effect of a ► priming drug injection or ► conditioned stimuli are then assessed on lever responding. The term relapse is perhaps a misnomer, since animals do not self-administer during these test sessions; however, the procedure has provided a robust model to examine important influences on drug seeking. It has been shown that conditioned stimuli, ► stress, or a priming injection of drug can reinstate responding (Shaham et al. 2003).

Another important trend in the self-administration literature has been the application of behavioral economic principles. The theoretical constructs of supply, demand, consumption, and price have been usefully applied to the analysis of drug intake. Price can be manipulated by changing the response requirement for a fixed unit dose of drug. Alternatively, the response ratio can be fixed (e.g., FR1) and the unit injection dose reduced as might occur in an assessment of threshold (illustrated in Fig. 1). Either way the theoretical issues are the same. A behavioral economic analysis of the relationship between consumption and price offers a relatively new way of assessing reinforcing strength (Hursh 2000).

As stated previously, the majority of self-administration studies have used the intravenous route of administration. Studies of alcohol intake have quite naturally used the oral route. Rodents are generally reluctant to drink alcohol without some encouragement. ► Schedule-induced polydipsia has been used to induce higher levels of alcohol intake. Similarly, intake can be increased by sweetening the alcohol solutions. After a reasonable intake level has been established then the sweetener is faded out over days. The neurobiology of both appetitive and consum-matory aspects of alcohol intake is currently being assessed in rodent studies through analysis of different strains, knockout mice, and through ► selective breeding programs for alcohol preferring animals.

Intragastric, inhalation, intraventricular, and intrace-rebral routes have all been used in self-administration experiments. The ► pharmacokinetics of each route is different; the rate of drug delivery to the brain necessarily affects the reinforcing efficacy.

Self-administration by the intracrerebral route is a special case which offers a unique perspective on brain circuitry involved in drug reinforcement. Since the first report by Olds et al. (1964) there have been about 50 papers describing self-administration of drugs into various brain regions. Interestingly, nondrugs of abuse have been reported to support operant responding. Because drugs are introduced directly into circumscribed brain regions, they can have a purely local effect which is quite different from a systemic injection. For example, Liu and Ikemoto (2007) have shown that muscimol (a GABAa agonist which would produce local inhibition) is self-administered into the median raphe nucleus. By contrast, picrotoxin (a GABAA antagonist which would produce neuronal

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Defeat Drugs and Live Free

Defeat Drugs and Live Free

Being addicted to drugs is a complicated matter condition that's been specified as a disorder that evidences in the obsessional thinking about and utilization of drugs. It's a matter that might continue to get worse and become disastrous and deadly if left untreated.

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