Reinforcing Effects

The reinforcing effects of a drug are determined by demonstrating that self-administration of the drug plus the solution it is dissolved in (vehicle)

occurs in excess of self-administration of the vehicle alone. When drug-reinforced behavior is readily achieved in the animal laboratory, it is usually a good predictor that the drug has considerable abuse liability in the human population. The reinforcing effects of PCP have been studied using two animal models of self-administration, oral and intravenous. The intravenous route of self-administration requires the animal to make a specified number of responses on a lever or other manip-ulandum within a predefined time—then a fixed dose of the drug is delivered by an infusion pump via a catheter that is surgically implanted in a large vein that leads to the heart. Studies from various laboratories have demonstrated that intravenously delivered PCP functions as a reinforcer for rats, dogs, monkeys, and baboons.

Drugs that are chemically similar to PCP are also self-administered intravenously. These include drugs that have similar receptor-binding sites in the brain, such as ketamine, (+ )SKF-10,047, dexoxadrol, and cyclazocine; and phencyclidine-like drugs that function as noncompetitive antagonists at the NMDA receptor, such as dizocilpine. Phencyclidine and dizocilpine self-administration is more reliably obtained when the animal has a history of self-administration of a drug with similar pharmacological or discriminative-stimulus effects. It has also been found that drugs that share discriminative-stimulus effect with PCP, such as ( + )SKF-10,047, ketamine, PCE, TCP, and etha-nol, are readily substituted for PCP in self-administration studies.

Oral PCP self-administration is established by presenting gradually increasing concentrations of PCP after the animal is given its daily food ration. After sufficient quantities of PCP are consumed, food is given after the drug self-administration session, and PCP consumption usually persists. This procedure provides a long-term stable baseline to examine variables that affect PCP-reinforced behavior. For example, alternative nondrug reinforc-ers, such as saccharin, reduce PCP-reinforced responding up to 90 percent of baseline if the FR for PCP is high or if the PCP concentration is very low. Free access to food decreases PCP self-administration, while even small reductions in the daily food allotment markedly increase PCP self-administration. Concurrent availability of ethanol also reduces PCP-reinforced responding.

A limited amount of information is available concerning drug pretreatment and PCP self-administration. Buprenorphine and dizocilpine pretreatment both resulted in dose-dependent decreases in PCP self-administration; however, potential treatment drugs such as fluoxetine and car-bamazepine had no effect. Treatment with other drugs such as AMPHETAMINE or PENTOBARBITAL had a biphasic effect on PCP self-administration. Low doses of the pretreatment drugs increased PCP self-administration, and high doses decreased PCP self-administration.

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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