Lec 1 Flashcards
Define Dependance according to the DSM IV and link this to animal models. How does this link to animal models? How can we model dependance using animal models?
- Tolerance - increased dose of the drug needed to achieve the same high
- Withdrawal - manifested by the following 1. withdrawal syndrome. 2. same or closely related substance is taken to relieve or avoid withdrawal symptoms.
> Withdrawal symptoms associated
Frustration bursting
- Time - time spent drug seeking/ amount of time - Drug seeking behaviour
> Self-administration schedules
2nd order ratio - can use this ratio to test drug seeking and drug taking behaviour.
- Continued use despite knowledge of persistent or recurrent physical or psychological problems that is likely to be exacerbated by the substance e.g depression or continued drinking despite a stomach ulcer.
> Continue use despite harmful consequences - electroshock with administration and continued use of substance despite harmful consequences
> Progressive ratio defines the breaking point and which the animal
> Pathological dependance (addiction) is the compulsive drug use maintained despite adverse consequences for the user - this pathological behaviour appears only in a small proportion of drug users (15-17%)
What is the key neuronal project that underlies all abusive substances
Ventral Tegmental Area Projects to nucleus accumbens.
Describe intravenous self-administration methods and criteria to demonstrate reinforcement
> Intravenous self-administration can be used to measure the positive reinforcement of a drug. Train rodents to lever press for an addictive substance such as cocaine then monitor the maintenance of drug taking of the new substance
> Drug reinforcement is when the event (drug administration) that follows a behaviour (lever press), reinforces the possibility of a future response. Behaviour is strengthened by the event that follows the behaviour. A drug is said to be reinforcing if the response is above the response for saline or other control conditions.
> Form of operant conditioning - considered the most valid experimental model to test the drugs reinforcing effects and used to test drug-seeking and drug-taking behaviour.
> Drug reinforcing effects drive addiction -> if cancel out the reinforcing effects then don’t see addiction. However, not just blocking the pharmacological effects of a drug but also need to consider conditioning factors, learning associated with drug taking. breaking associations is the real challenge.
> drug obtained via intravenous injection via catheter usually inserted into jugular vein. catheter connected to an infusion pump containing drug solution and lever press operates administration. The rats can learn to administer a positively reinforcing drug by pressing the lever.
> lever pressing responses will occur in higher frequency is the drug is reinforcing. If the drug is not reinforcing then will get diminished response.
> administration of drugs positively reinforces the lever-pressing behaviour.
What is the relevance of drug-seeking behaviour to addiction?
> drug seeking is associated with positive reinforcing effects of drug that are responsible for drug-seeking behaviour
> Drug seeking behaviour is controlled by four main processes: Aversive effects of drugs, discriminative effects of drug, positive reinforcing effects of drug and stimuli conditioned to effects of drug.
What is condition place preference? what does conditioned place preference tell us?
> In conditioned place preference a distintive environment is paired repeatedly with the administration of a drug and a different environment is associated with an undrugged state. Typically differ with respect to visual, tactile or odour cues. After several conditioning trails subjects are allowed to access both compartments. Drug seeking behaviour shown by an increased amount of time in the compartment that was previously paired with the drug. Often assumed that distinctive environmental cues take on secondary (conditioned) reinforcing effects due to their association with the drug
> tells us about drug seeking behaviour
What is the benefit of the self administration model?
Many studies have shown many same substances that are addictive in humans also addictive in animals. The parallel results between human and animals drug literature validate the use of the animal model and suggest that the use of this model may lead to a better understanding of human drug taking behaviour.
What is the importance of conditioned stimuli?
> environment associated with a drug by means of classical conditioning.
> environment can serve as a secondary reinforcer.
> Act as a que that significantly influences behaviour.
> example - animal is placed in a test chamber and the stimulus light is turned on this is associated with drug delivery. When turned off lever presses have no consequences. lever-pressing will therefore only occur at a high rate when the light is on. The light is established as a discriminative stimuli/cue that controls behaviour.
> Animal will emit high frequency lever-pressing response when only consequence is the light. Such responding persists over long periods of time without administration of second-order schedule of reinforcement
Then present the stimuli but no drug and monitor behaviour. Persistence of responses without administration of the drug. Provide a model of persistence of drug taking.
What is addiction often co-morbid with?
Depression and anxiety disorders - can produce changes in mood! relief from withdrawal symptoms, improvement in cognition (nicotine), escape of reality.
what are the 3 animal models for studying addictive drugs
- Drug self-administration
- Drug discrimination - identification of characteristic effects of drug
- Neuroadaptation - changes associated with repeated administration - tolerance, withdrawal
What are the criteria for demonstrating drug reinforcement?
- Dose-response relationship - Animals will adjust the rate of drug administration to maintain a stable rewarding blood level of drugs. A dilute dose of the drug is administered faster than a concentrated dose. The higher the dose of the drug then the more reinforcing it is and higher number of responses.
- Vehicle substitution - take drug away and look for disruptions in behaviour. Frustration bursting
- Lever Reversal - monitor how quickly the animal moves to the active lever
- Reinforcing efficacy of the drug - The likelihood a drug will serve as a reinforcer under various experimental conditions e.g progressive ratio
Outline the different schedules for self-administration
- Fixed ratio: more responses the animal makes the more drug it gets. A schedule in which a response is reinforced only after the animal has responsed a fixed number of times.
- Dose response curves: As increase dose then individuals begin to regulate their intake. The peak tells up about the drugs reinforcing ability and usually see inverted U shaped curve.
- Fixed interval - Once the time elapses, first response delivers the drug. Response independent.
- Progressive ratio: Higher-order schedule that requires the animal to emit an increasing number of responses for each successive reinforcement. This defines the breaking point.
- Second-order (or higher) schedule - A schedule requiring the completion of an individual component of the schedule that produces availability of a terminal event. Responses can be maintained for long periods of time by conditioned reinforcers (e.g flash of light) and animals lever press for secondary reinforcement and can be paired with a fixed interval of time (e.g flash every 10s). First interval in the absence of cocaine = drug seeking. Second interval is with cocaine = drug taking. If don’t get cocaine see an extinction in behaviour.
What are the key features indicating dependance (only seen in 15-17% of drug users)?
- See persistance in responding even though drug is no longer available. Fustration bursting.
- High motivation for the drug can be demonstrated by high breaking points in progressive ratio schedules.
- Drug use despite harmful consequences - resistance to punishment. Gives insight into human drug taking behaviour
How is impulsivity linked to addiction?
Studies using the delayed discount task show that if an individual is impulsive then will take immediate smaller reward rather than greater reward in future - linked with addiction. Impulsivity has been shown with cocaine addiction
What is BP897?
anti-craving drug as it only effects the first interval of a second order schedule. In animals, a dose response curve shows the greater dose of BP897 pretreated with then the greater the reduction in craving/drug-seeking. However, BP897 was not translatable into humans but was a good strategy for developing cocaine dependance research
What is baclofen?
GABAb agonist. GABAb agonist inhibits the release of neurotransmitters such as DA, NA, 5-HT and glutamate. Shown that given before cocaine administration that this attenuates cocaine self-administration.
