addiction in animals Flashcards
what are models of addiction
non contingent
self administration (contingent) either operant or non operant
what is addiction
a brain disorder characterised by compulsive engagement in rewarding stimuli despite adverse consequences
addiction exacts an “astoundingly high financial and human toll” on individuals and society as a whole through:
adverse effects of drugs and associated healthcare costs
long term complications (e.g lung cancer with smoking tobacco, liver cirrhosis with alcohol, and meth mouth from intravenous meth)
functional consequences of altered brain function and consequent loss of productivity
what characteristics of animal drug studies resemble human behaviour
both humans and labratory animals will voluntarily take drugs by different routes (orally, iv etc)
if unlimited intravenous heroin or cocaine is provided both humans and animals can easily overdose
mice and rats voluntarily drink large quantities of alcohol leading to strong intoxication
what is a main question of validity of animal models of drug addiction
do animals really engage in human like drug taking or are we anthropomorphosising
need a strong scientific definition of drug taking behaviour
what are assumptions of animal models of addiction
it is widely assumed that the neurochemical and neuroanatomical substrates involved in drug taking behaviour are similar in rodents and humans however this is quite an assumption
most research is based on cocaine or amphetamine addiction due to mix of historical and practical reasons
how do cocaine and amphetamine act
they are the most commonly studied drugs
cocaine acutely blocks dopamine reuptake
amphetamine enters presynaptic terminal and causes vesicular monoamine transporter VMAT to release dopamine intracellularly; results in dopamine being reverse transported; acts on endogenous dopamine terminals to increase the level of dopamine
what is non contingent drug exposure
experimenter administered usually via intraperitoneal injection
can measure stimulant induced increase in locomotion, increases with additional injections (sensitisation), conditioned place preference
what are pros and cons of non contingent drug exposure
pros:
easy to perform
results in high volume of data
makes it amenable to complex molecular cellular and circuit integration not possible with more complex models
cons:
it is highly unlikely that someone will give you a surprise injection of cocaine into your stomach
thinking psychologically about it, we are missing key aspects of behaviour; seeking, motivation, working for the reward
all of which are key especially in terms of addictive behaviour as these are the behaviours that become compulsive
what is non operant contingent exposure
in rodents this is restricted to oral self administration
translationally this should only be used with alcohol, MDMA, and cannabinoids as other drugs are rarely taken via this route; however this has not stopped lots of people studying cocaine and heroin etc
despite the fact that this route is very different pharmacokinetically than that used by humans
what are benefits of non operant self administration
rodents typically do not drink alcohol when first exposed to it (much like humans)
they are weaned onto it either through sweetening or by gradually increasing the concentration of alcohol (like humans)
after such training mice and rats can readily and voluntarily drink up to 40% alcohol solutions
will readily drink to intoxication (like humans)
what are cons of non operant self administration
often “sped up” by exposure of highly concentrated alcohol vapour
results in high levels of voluntary drinking but is essentially non contingent
what is operant self administered exposure to drug
rodents work to administer drug eg via nose poke or lever press
usually via and iv catheter
a model of the acquisition of self administration
what are ways of measuring operant self administration of drugs in animal studies
fixed ratio: after a certain number of work (e.g lever presses) the drug will be given, an FR5 would mean the drug would be given every 5 lever presses
measures the motivation to get the drug
progressive ratio:
where each drug delivery the number of lever presses is increased; e.g 1,2,4,8,16
used to measure the breakpoint; maximum drive to get the drug
what are benefits of operant self stimulation
we have now regained some important aspects of behaviour
the rodent has to work for the drug, it has to approach the lever of its own will (goal directed behaviour)
also some consitencies with human behaviour; need to enforce timeout periods or the rodent will overdose
while difficult it is high throughput enough to do complex cellular molecular and circuit investigations
allows the identification of risk factors for acquisition that opposed to epidemiological studies can be causally tested
examples are: sex F>M impulsivity H>L sweet preference: H>L stress H>L exercise L>H
how is impulsivity tested in rats and how does it effect studies
rodents are given a choice:
one lever gets 1 pellet immediately
the other gets 4 pellets after a delay up to 20s later
rats split into 2 groups; impulsive (small immediate reward) or low impulsive (bigger delayed rewards), can be used to test for risk in drug studies
what are cons of operant self administration
very rarely are we given what we want just by pressing a lever
operant self stimulation can be supported by many non addictive substances; food, water, even lights
is it addiction or just reward learning
not as simple as it sounds; requires a lot of training (auto shaping, sucrose fading)
only 20% of individuals that regularly take drugs become addicted
this is a good model of acquisition of drug taking
what is relapse
drug addiction can be conceptualised as a chronic relapsing disorder characterised by recurrent bouts of drug use with intervening periods of withdrawal and abstinence
relapse may in fact represent the single most predictive outcome of a diagnosis of addiction
one of the greatest challenges for treatment
how is relapse modeled in animals
the resumption of a previously reinforced response when the unconditioned reinforcer or reward is presented non contingently after a period of extinction training
what are benefits of animal models of relapse
seems to capture a key aspect of addiction
anthropomophically mimics the human problem
has helped to identify causally specific events or drugs that can induce relapse:
the drug itself
cues associated with drug use (for rat a lever, for humans a lighter/ needle etc)
stress (mild foot shock, food deprivation and social isolation can all induce relapse in rats)
what are cons to animal models of relapse
all animals exposed to cocaine relapse; this is not the case with humans; something is missing
this model requires extinction of the response; rarely happens in humans and so is of limited value
however some treatment centres have started using behavioural extinction as a means to treatment
what are benefits of a multidimensional study for addiction
the animal models examined so far investigate a specific aspect of drug taking, seeking or relapse which are helpful but not necessarily a model of addiction
there is need for a multidimensional model incorporating all of these aspects
e.g addicted individuals not only consume large amounts of drugs but are also unable to repress their drug use regardless of its consequences
also drug seeking is not the same as drug taking, seeking requires many steps such as finding money, implements and tools and purchasing the drug
a “ true model should also take into account the small proportion of individuals who regularly use drugs that transition to addiction”
what is a DSM compatible model of addiction
DSM requires 3 out of 7 criteria to be present in the last 12 months;
most notably;
inability to refrain from drug seeking
high motivation for the drug
maintained drug use despite negative consequences
these can be modelled in rodents:
drug seeking periods when the drug is not available and signalled as such
high break points during progressive ratio schedules of reinforcement
persistence of self administration despite punishment by contingent electric foot shocks
