Chapter 3: How we Adapt to Drugs - Tolerance, Sensitization, and Expectation

Nocebo effects are _____ to the drug the participant believes he or she is taking. E.g., participants taking placebos in a tricyclics drug trial are more likely to report adverse effects typically associated with tricyclics than are placebo-group participants in SSRI drug trials, as such adverse effects do not typically occur in SSRI treatments.

specific

Combined placebo effects, resulting from the learned associations between particular stimuli and pain relief, involve changes in activity in the _____ - a region of the brain that processes reward.

striatum

Like tolerance, sensitization may also be conditioned to a particular environment. It can be demonstrated in two ways:

1. As with tolerance, if sensitization develops in response to repeated administration of a drug in a specific environment, then sensitization will be greatly diminished or will not appear at all when the drug is given in a different environment. 2. If sensitization results from repeated injections in a specific environment, then that environment will act as a CS of a drug-like CR. If you place an animal in the environment after a placebo injection, it will show increased activity.

Opponent Process Theory:

Abused drugs stimulate an A process that creates a euphoric a state, but that soon after, a compensatory B process is evoked that creates a dysphoric b state. At first the A process dominates, but once the B process kicks in, it very quickly cancels out some of the a effect. As the drug wears off, so too does the A process, but the B process ensures for a while. This means that the dysphoric state b occurs at the end of the process before the effect normalizes.

Pharmacodynamic tolerance:

Arises from adjustments made by the body to compensate for an effect caused by the continued presence of a drug - it is believed that these adjustments are a result of homeostasis.

Pharmacokinetic tolerance:

Arises from an increase in the rate or ability of the body to metabolize a drug, resulting in fewer drug molecules reaching their sites of action.

Novel Environments:

Drug effects are different when the drug is administered in a novel environment. If the drug is administered in a novel environment, the amount of locomotor stimulation is considerably more than would be seen if the drug had been administered in a familiar setting.

Tolerance:

Drug tolerance is defined either as the decreased effectiveness of a drug that results with repeated administrations, or as the necessity of increasing the dose of a drug in order to maintain its effectiveness after repeated administrations.

Self-Administration

It has been shown that drugs may have different effects when they are self-administered compared to when the person or laboratory animal has no control over drug administration.

Sensitization:

Most of what we know about sensitization comes from studies of the behavioral activating effects of variety of drugs, including cocaine, amphetamine, nicotine, alcohol, phencyclidine, and opioids. At low doses, all of these drugs produce an activating effect when first given to laboratory animals. Sensitization can occur after only a single low dose of the drug. With repeated low doses, there is a rapid and progressive increase in behavioral activation with each administration.

Classical Conditioning of Compensatory Responses

Sometimes, the stimulus paired with a drug, when presented in the absence of the drug, produces a physiological response (a CR) opposite to the UR produced by the drug. This can occur if what is being conditioned is not the effect of the drug itself, but the body's attempt to resist the effect of the drug - the compensatory effect.

The Placebo Effect

The expectation of being influenced by a drug is largely what drives the placebo effect. It is thought to be responsible for a considerable degree of the therapeutic effect of many medications.

The Nocebo Effect

The nocebo effect means that a placebo can generate adverse effects in participants.

Dependence

The terms dependence, physical dependence, and physiological dependence can be used interchangeably to indicate a state in which withdrawal symptoms will occur when drug use stops. These terms do not imply anything about compulsive drug use, abuse, or addiction.

Behavioral tolerance:

This type of tolerance can involve both operant and classical conditioning processes.

Operant Conditioning of Drug Tolerance

Tolerance can develop due to operant conditioning, for example, in the research by Vogel-Sprott. The effect of alcohol on the pursuit rotor task had no significance of the control group, who were not informed that the alcohol was having an effect on them. The participants in the experimental group, however, found that the disruptive effect of the alcohol had significance for them, and so tolerance developed.

Cross-tolerance:

Tolerance to one drug may well diminish the effect of another drug. Is usually seen between members of the same class of drugs (e.g., all opioid drugs show cross-tolerance).

Withdrawal:

Withdrawal symptoms are physiological changes that occur when the use of a drug is stopped or the dosage is decreased.

Cross sensitization:

e.g., laboratory animals with a sensitization to morphine will also show an increased behavioral activation to cocaine and amphetamine. Even stress will sensitize a rat to the activating effect of many of these drugs. Stress-induced cross sensitization of drug effects appears to result from the impact of the hormone corticotropin-releasing factor on the development and functioning of the meso-limbic and meso-cortical dopamine pathway.

Tolerance can be influenced by learning - through _____ with a drug, an organism can learn to decrease the effect that the drug is having.

experience

Brain Mechanisms Involved in the Placebo Effect:

fMRI imaging has found increased activity in the orbitofrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, insular cortex, and midbrain periaqueductal gray during the anticipation of pain. Decreases in these same regions appear during placebos.

Tolerance will develop (or will develop much more quickly) only in circumstances where a drug places a demand on an organism's _____ mechanisms. Tolerance to drug effects and are not detected or that do not disrupt functioning does not develop.

homeostatic

One way sensitization differs from tolerance is its _____. Even a single dose of a drug can create long-lasting sensitization. Both conditioned and unconditioned sensitization can last as long as a year after drug exposure in rats, and there are no reports of it dissipating over time. In fact, there is evidence that sensitization might increase with time.

persistence

When _____ tolerance takes place, all effects of the drug will be diminished because of the diminished concentration of the drug at the site of action.

pharmacokinetic

Sensitization appears to be a mirror image of _____, except that the conditioned response is a drug-like response rather than a drug-opposite response.

tolerance