Drugs as Discriminative Stimuli

discriminative stimulus

stimulus (such as the effects of drugs or of drug withdrawal) that signals the availability of a reinforcer as a consequence of performing an operant

state-dependent learning

information learned during an altered state can be better recalled while in the same altered state than while not in the altered state

drug discrimination

subjects learn to recognize the effects of a drug and report its presence by emitting behavioral responses to either obtain a reward or to avoid an aversive stimuli; in vivo technique with the greatest degree of pharmacological specificity

drug discrimination design

-animal is pretreated with either a training dose of drug or vehicle on different days, each of which is paired with a different lever that, when the subject presses the correct lever, results in reinforcement until the subject can distinguish between which interoceptive state (drug or vehicle) corresponds to which lever

-after training, a test drug is administered and both levers are active for reinforcement to determine if the test drug produces subjective/interoceptive effects similar to the training drug

drug discrimination design (humans)

-participants are given one of two drugs (and are told what it is) and verbally asked to distinguish between them

-after initial training, drug is given and participants answer questionnaires related to subjective effects of the drug and are reinforced with money if they correctly identify the drug

-participants who are most accurate are selected for testing phase where they received either training drug or test drug and are reinforced with money regardless of if answer is correct

dependent measures of drug discrimination

-% drug lever responding

-response rate

-first FR earned

-questionnaires to determine mood/other drug effects (in humans)

% DLR (% drug lever responding)

% of responses on training drug-paired lever; test drugs that produce similar subjective effects to the training drug result in higher values

response rate

measure of behavioral activity; can be used to determine if the test drug is behaviorally disruptive

first FR earned

which lever the subject earned reinforcement from first; used to determine the subject's initial perception of the test drug's effects

tenets of drug discrimination

-model of subjective effects in humans

-discriminative stimulus effects are centrally mediated (drug must act on CNS)

-high degree of pharmacological specificity

-training dose influences substitution levels of test drugs/how quickly subjects acquire ability to discriminate

-generalization across ROAs

-tolerance to discriminative stimulus effects doesn't develop under normal training conditions

DD models subjective drug effects in humans

correspondence between drug-like SD effects in animals and drug-like intoxication/subjective effects in humans (ex: cannabinoids that produce THC-like SD effects in rats are mostly the same cannabinoids that produce cannabis-like effects in humans)

SD effects are centrally mediated

discriminated drug must act on the CNS to exert SD effects; centrally active antagonists can block the SD effects of drugs, but peripherally-restricted antagonists do not

high degree of pharmacological specificity

-drugs usually need to have similar mechanisms of action in order to produce SD effects similar to the training drug (ex: nicotine and arecoline SD effects are mediated by distinct cholinergic receptors in the CNS)

-drugs that produce some similar effects to the training drug won't necessarily substitute for training drug (ex: PCP produces some analgesic and dissociative effects, but opioids and hallucinogens do not substitute for PCP)

-drugs that act on different receptor subtypes do not typically substitute for training drug (ex: can disentangle whether a drug has action at mu or kappa opioid receptors (or mixed action) based on substitution pattern)

substitution levels, how quickly

increases in training drug dose influences _____ of test drugs and also _____ subjects acquire the ability to discriminate SD effects (rightward shift in DEC and fewer sessions, respectively)

generalization across ROAs

the same drug administered via different routes of administration produces substitution (ex: inhaled THC can be discriminated the same as injected THC)

tolerance

______ to SD effects does not develop under normal training conditions

acute dependence

withdrawal can be precipitated by giving an opioid antagonist following an acute administration of an opioid agonist (treatment does not need to be chronic)