4.1. Psychopharmacology methods: Animal models

Unconditioned animal behavior (no learning required)

- Simple behavioral observation

- Motor activity

- Analgesia

- Anxiety

Locomotor activity chamber

measures horizontal and vertical movement

Analgesia

Tail flick and hot plate tests measure analgesia (reduced pain

sensation)

Elevated plus maze

measures anxiety

light-dark box and open field

measure anxiety

Conditioned animal behavior

Classical conditioning (Pavlov)

1. Fear conditioning

2. Conditioned place preference

Instrumental conditioning (Skinner)

2. Operant chamber learning

Fear conditioning

a test of learning and remembering emotional (aversive) events.

Drug properties: Stimulus properties

Informal definition: What does the drug feel like?

Paradigm used: Drug discrimination

Drug properties: Rewarding properties

Informal definition: Do you 'like' the drug?

Paradigm used: Conditioned place preference

Drug properties: Reinforcing/incentive

properties

Informal definition: Do you 'want' the drug?

Will you work for the drug?

Paradigm used: Self-administration

Drug discrimination

is used to assess the stimulus properties

Drug discrimination (2)

animals classify drugs just like humans.

highly sensitive and accurate predictions

Conditioned place preference

is used to assess rewarding properties

Conditioned place preference (2)

conditioned place preference (CPP).

conditioned place aversion (CPA).

Drug self-administration (1)

"Will you work for the drug?"

"Do you 'want' the drug?

Drug self-administration (2)

Animals will self-administer most drugs that people abuse.

Some drugs that maintain self-administration:

Some drugs that do not:

(most hallucinogens are not self-administered by animals)

Reward vs. reinforcement

CPP measures reward.

Self-administration measures reward and reinforcement

Fixed ratio (FR) schedule

reinforced after every nth response

Variable ratio (VR) schedule

reinforced on average after every nth response

Progressive ratio (PR) schedule

each reinforcement requires more responses

Drug self-administration (fixed ratio schedule) (1)

Rats adjust rate of cocaine self-administration according to dose.

The dose-response curve for a fixed-ratio (FR) schedule

has an inverted U shape

progressive ratio (PR) schedule

is the highest ratio attained before the animal "gives up."

The breakpoint is often used as a measure of drug motivation.

"How hard are you willing to work for the drug?"

Comparison of FR and PR schedules

Rate of responding on FR schedules can be an ambiguous

measure.

Progressive ratio schedule

Dose-response curve just increases for PR

(not inverted U like FR)

Comparison of FR and PR dose-response functions

FR dose-response curve inverted U shape

PR dose-response curve only increases

How do you tell if a rat is "addicted"?

- controlled and uncontrolled drug use

- Addiction is not just the taking of drugs but compulsive drug use maintained despite adverse consequences

Newer animal models of addiction

animal models that focus on addiction

The aim is behavior that more closely aligns with DSM criteria for substance use disorders:

Escalation of use

Difficulty stopping

Continued use despite negative consequences (resistance to punishment)

Use to the exclusion of other behaviors