neurobiology 1 Flashcards
Describe the dopamine reward system
The mesolimbic pathway involves the transportation of dopamine from the ventral tegmental area, which is located in the midbrain, to the nucleus accumbens, where it affects motivation for rewarding stimuli, the perception of pleasure, and reward-related motor function learning. It is the most significant neural pathway in the brain in which changes occur in all known forms of addiction. The mesocortical pathway involves projections of dopamine from the VTA to the frontal cortex. Together these pathways are referred to as the mesocorticolimbic pathway.
What is dopamine
• Dopamine is a neurotransmitter: a chemical released by neurons to send signals to other neurons.
D (or any neurotransmitter) is released from one neuron at the presynaptic nerve terminal. Neurotransmitters then cross the synapse where they may be accepted by the next neuron via a (dopamine) receptor. The action that follows activation of a receptor site may be either depolarization (excitatory) or hyperpolarization (inhibitory). A depolarization makes it more likely that an action potential will fire; a hyperpolarization makes it less likely that an action potential will fire.
Briefly describe the role of dopamine in cocaine addiction
Cocaine binds to the dopamine uptake transporters, especially in areas that are rich in dopamine receptors such as in the VTA and the nucleas accumbens.
As the uptake transporters are occupied, this then prevents the reuptake of dopamine from these areas and dopamine builds up. Thus more dopamine is available in system for a long period of time, leading to enhanced dopamine reward.
Addiction to cocaine may therefore be driven by the very strong dopamine reward.
Breifly describe the role of dopamine in heroin addiction
The effects of heroin occur very rapidly when injected
Enzymes convert heroin into morphine, which binds to opiate receptors including in the reward pathway (VTA and nucleas accumbens) and in the pain pathway (thalamus, brainstem, and spinal cord) which leads to analgesia (inability to feel pain).
When morphine binds to the opiate receptors on a neuron, it causes it to reduce its release of GABA (Gamma-Amino Butyric acid), which normally inhibits the release of dopamine from other neurons.
As dopamine release is no longer inhibited, this means that more dopamine is released and binds to DA receptors than usual, thus dopamine reward is enhanced.
Heroin addiction may therefore also be driven by the strong dopamine reward.
What is GABA
Gamma-Amino Butyric acid
• GABA is an inhibitory neurotransmitter that is important in a whole range of functions related to memory, mood etc.
• Secretion of GABA usually inhibits the release of dopamine from other neurons.
Breifly describe the opponent process model
Solomin 1980
The drug reward process from repetitive drug use is upset by opponent processes that have homeostatic function following drug euphoria to restore baseline levels. • The first component he called the A reaction, In the context of drug addiction this would be the euphoria experienced after drug administration. It is short-lived and intense. For example, while receiving an award, you may feel great joy at the moment when you are handed your medal or certificate. This response probably correlates with neural activity in the brain; it is quick and almost simultaneous with experience of the emotion-causing stimulus.
• The B reaction is opposite from the A component in hedonic value. In other words, if the A reaction is a happy emotion, the B reaction is sad, and vice versa. In the context of drug addiction this would be withdrawal. The B response is slower to build and slower to decay. An hour after getting an award, you may feel a bit let down, but the feeling gradually disappears toward the end of the day.
What is the key aspect of the opponent processes model
They key to Solomon’s theory of addiction is that as an event is repeated the B component becomes larger while the A component becomes smaller. The result, sometimes, is a complete reversal of emotion. An event that was initially fun becomes boring, or an event that was initially terrifying becomes fun.
Very brief summary of koob and lemoals allostatic model of drug addiction
- An opponent processes model
- Allostasis in drug use refers to alterations to the reward pathways due to repetitive substance use. These changes lead to the development of addiction.
- Begins with administration whereby the a process occurs, followed by a minor b process. With repetitive admnistration the b process, which is withdrawal symptoms, becomes larger. These constitute the changes in reward pathways that lead to addiction.
- This increasing b process is known as the allostatic load.
- As the allostatic load increases, the individual seeks to escape it by further drug administration. Thus a spiral of addiction ensues, which is proposed to have three stages.
- There are three stages to the cycle: Bing/intoxication, withdrawal/negative affect and preoccupation/anticipation
Describe the binge/intoxication stage of koob and lemoals model
Can be explained in terms of the a-process in the opponent processes model
Initial positive reinforcing effects of drugs, mediated by dopaminergic pathways in the medial forebrain i.e. ‘ brain reward pathways.’
With initial use, reward thresholds are temporarily reduced and a second use can produce an increased euphoric effect, thus increasing the likelihood of further repetitions. Impulsivity and positive reinforcement often dominate the first stages, driving the motivation for drug seeking. (It is not until there are further repeated uses that reward thresholds begin to increase, making the a process smaller.)
Describe the withdrawal/ negative affect stage of koob and lemoals model
Can be explained as a b-process
Chronic use leading to down-regulation of dopaminergic and hypoactivity in brain reward regions- this is where they develop the allostatic state.
Defined by chronic irritability, anxiety, depression, anhedonia, low motivation for natural rewards; termed the dark side of addiction
This is the stage in which allostasis occurs via two processes:
1) Reward system becomes compromised
2) Stress systems become recruited
There is a lot of neurobiology behind this, but mainly this involves in stage 1) the increasing of dopamine reward thresholds, and in stage 2) the activation of the HPA axis
Describe the anticipation/preoccupation stage of koob and lemoals model
Craving- key element of relapse
Due to activation of anti-reward systems, individual experiences protracted abstinence: refers to stage where patients continue to experience difficulties in affective processing (i.e. almost like an extended withdrawal period in terms of low mood and irritability) even after ceasing drug taking behaviour.
This may compromise recovery during protracted abstinence by causing stress-induced relapse
Heightens sensitivity to acute and chronic stressors in the environment that can trigger relapse
Neuro-adaptational changes can be relatively long-lasting, meaning relapse can occur over long intervals.
Evidence for binge/intoxication stage
Supported by the firmly established role of mesocorticolimbic dopamine pathways in response to almost every kind of addictive substance- shows that the initial stage of developing an addiction is due to reward, or ‘a process.’
Evidence for bingeintoxication and part 1) (increased dopamine threshold) withdrawal negative affect stages
Hernandez et al 2006
Dopamine levels were measured in the rat nucleus accumbens by means of in vivo microdialysis. Delivery of rewarding medial forebrain bundle stimulation at a low rate (5 trains/min) produced a sustained elevation of dopamine levels, regardless of whether train onset was predictable. When the rate of train delivery was increased to 40 trains/min, dopamine levels rose rapidly during the first 40 min but then declined toward the baseline range. The rewarding impact of the stimulation was reduced following prior delivery of stimulation at the high, but not the low, rate. Further demonstrates the involvement of nucleas accumbens in dopamine reward, thus supporting Koob and LeMoals proposed anatomical basis for the bing/intoxication stage. Also supports that as a behaviour is repeated, the dopamine reward, or a process becomes smaller, thus supporting Koob and LeMoals theory of within-systems adaptations that occur in the withdrawal stage that contribute to allostasis.
Evaluation of koob and lemoals model
- There are some issues not addressed by opponent processes models
- For example, animal studies suggest that priming doses of drugs are more effective at drug reinstatement than antagonist drugs which mimic withdrawal symptoms. Contradicts the idea the addiction is due an attempt to escape withdrawal.
- Also, relapse can occur well after withdrawal, whereas koobs model suggests that the individual transition into addiction as a result of escaping withdrawal symptoms.
- Some drugs, such as nicotine, produce minimal withdrawal symptoms in comparison to drugs like heroin, and yet they are highly addictive.
Describe the neurobiology of the binge/intoxication stage
Involves largely the most sensitive sites defined by the lowest reward thresholds i.e. the trajectory of the medial forebrain bundle that connects the ventral tegmental area (VTA) to basal forebrain areas such as the nucleas accumbens (i.e. the mesolimbic/reward pathway), and also the central nucleas of the amygdala which projects onto the nucleas accumbens.
