van den oever Flashcards
aim: van den oever
investigate changes in molecular composition and function of synapses in media prefrontal cortex upon re-exposure to heroin cues after long-term abstinence from self-administration
procedure stage 1: self administration
experimental group - trained to self-administer heroin every time they were presented with an audio-visual cue (light) if they poked their nose into a hole they would receive a dose of heroin
control group* - self administer a sucrose solution to ensure any neurobiological changes were just due to heroin
procedure stage 2: abstinence
after becoming addicted experimental group split into 2
- some rats kept in a separate cage for 21 days = forced abstinence
- other rats were put in a self-administration box for 21 days but didn’t receive heroin when nose poking = extinction
procedure stage 3: re-exposure to drug-associated cues
after 21 days=
- half abstinence rats and half extinction rats re-exposed to drug-associated cues for 60 min in OG self-administration boxes but NO heroin
- other half was placed into self-administration boxes but not exposed to drug-associated cues or heroin= control to confirm any synaptic changes were due to the drug-associated cues
procedure stage 4: analysis of composition and function of synapses in the medial prefrontal cortex
after stage 3 all rats were decapitated and brains were frozen and analysed using mass spec- which allowed the detection of subtle changes in receptor proteins in the synapses of the medial prefrontal cortex
results 1 and conclusions 1
after a period of abstinence/extinction from heroin rats exposed to cues showed a greater amount of drug-seeking behaviour therefore exposure to drug-associated cues can trigger a relapse back into drug-seeking behaviour recovering drug addicts need to be removed or avoided from cues
results 2
mass spec allowed them to look at post synaptic receptor called AMPA receptor in the medial prefrontal cortex which is a target for the neurotransmitter glutamate. after abstinence/extinction rats exposed to drug cues had lower-than-normal levels of AMPA receptors whereas rats self-administering & not exposed to drug cues and sucrose ones had normal AMPA receptors which affected rates of glutamate=lower levels of excitation in dopamine reward systems
conclusions 2
rats re-exposed to drug-associated cues related to heroin after some time of abstinence/extinction is linked to lower numbers of AMPA receptors on post synaptic neurons in medial prefrontal cortex the molecular composition and function of synapses had changed
How do neurons lose receptors?
brain has plasticity and can adapt to drug use in many ways.Neurons can reduce the amount of receptors by endocytosis this is where receptors are engulfed in a membrane and taken into the neurone. endocytosis of receptors results in reduced amount of activity for that neuron
follow up procedure
researchers used a new set of rats who were split into 2 groups the rats went through a similar procedure to the initial study EXCEPT for both self-administered heroin and both were exposed to drug associated cues in the period of abstinence/extinction HOWEVER 1 group was injected with a drug that prevented endocytosis
results 3
rats that hadn’t been injected showed significantly greater amount of drug seeking behaviour compared to those given the drug to prevent endocytosis
conclusion 3
this confirms a reduction in AMPA receptors in the prefrontal cortex as a result of being re-exposed to drug-associated cues is causing relapse back into drug-seeking behaviour therefore for treatment the medial prefrontal cortex could be a target to treat people’s addiction to heroin
generalisability PEEC weakness
Sample consisted of male Winstar rats which is not a representative sample of the target pop. This is a weakness as rat brains is different to human brains so the results of drug addiction in rats is less generalizable to humans. For example, mPFC is much smaller in rats which could influence how synapses change when exposed to heroin. However, the use of rats allows a great deal of control and it would be unethical to do this study on humans so using rats an appropriate sample for this type of experiment. For example, the decapitation of their heads would not be appropriate to do on humans
reliability PEEC strength
one strength is that the study used standardized procedures to ensure all rts had similar experiences. This is a strength as standardized procedures increase the reliability of the study because it makes it more replicable. For example, all rats trained with the same audio-visual cues they all also had 21 days in abstinence/extinction. Therefore the study is high in reliability. Furthermore, he also ensured the rats were all the same type and followed strict
applications PEEC
One strength is that it’s useful as it has practical applications for preventing drug addicts from relapse. This is a strength because heroin has a very high relapse rate with relapse causing serious consequences such as death. In particular, if drug addiction could be reduced then we would probably see a crime reduction associated with it. For example,drug therapy could be more developed to block changes in the synapses of the MPC as a result of being exposed to drug-related cues eg needles and friends. However, it’s unclear whether the same mechanisms are involved in human heroin addiction compared to rat heroin addiction and so a drug to prevent relapse may not work as well for humans as it does for rats
