Week 4 - Addiction Flashcards
What is anhedonia?
Inability of experiencing pleasure
What is hypodopaminergia?
Depletion of monoamine stores in the brain that can cause depressive-like symptoms
Hypodopaminergia is linked to ________ and ____________.
Anhedonia
Hypofrontality
What is hypofrontality?
Decrease in activation of prefrontal cortex, which compromises planning and decision-making
According to Volkow ND et al (2007), what did the brain scans of alcoholics show?
DA decreased and reported reduced reinforcing effects of MP
According to Volcow et al (1997), what id the brain scans of cocaine abusers show?
Decreased DA and reported reduced rewarding effects of MP
What is a challenging problem in the neurobiology of drug addiction?
To understand why some individuals become addicted to drugs while others do not.
What may be one of the keys to determining why some people become addicted to drugs while others do not?
Differences in reward circuits: dopamine levels and receptor levels
What happens when there is an over-expression of D2 receptors in the NAcb in rats addicted to alcohol?
Reduces alcohol preference and alcohol self-administration
What does a form on impulsivity in rats predict?
high rates of intravenous cocaine self-administration
A form of impulsivity in rats predicts high rates of intravenous cocaine self-administration. What is this associated with?
Changes in dopamine (DA) function before drug exposure
What did Dally et al find while using PET on rats and cocaine reinforcement?
D2/3 receptor availability is significantly reduced in the nucleus accumbens of impulsive rates that were never exposed to cocaine
In humans, what were low densities of dopamine D2 receptors associated with?
Decreased metabolism in the orbitofrontal cortex, where metabolism in other regions (basal ganglia) was relatively normal.
What psychological disorder is associated with decreased metabolic activity in the orbitofrontal cortex?
Obsessive-compulsive disorder (OCD)
What neurotransmitter does Ritalin (ADHD drug) bind to?
Dopamine (DA) receptors
Long-term addiction results in ____
Long-term adaptations to the dopamine system
reduced activity of dopamine
reduced experience of pleasure
Low levels of D2 receptors are associated with……
Increased desire for drugs
What are some criticisms for the brain-based view of addiction?
It disregards human decision making and choice
Addiction is not a disease in the classical sense:
- It’s a group of behaviours, not an illness in its own right
- It can’t be explained by the disease process
- There is no infectious disease or common biological degenerative or neuropathological problem
What is tolerance?
The need for increased amounts of the substance to achieve the desired effect
What is addiction a product of?
Environmental and physiological factors
How does the addiction cycle begin?
Positive reinforcement
How does the addiction cycle change over time?
Switches from positive reinforcement to negative reinforcement
What disorders contribute to addiction?
Impulsive and compulsive disorders
What did George Koob suggest about addiction?
An individual transits from an impulse disorder to a compulsive disorder, there is a shift from positive reinforcement to negative reinforcement
What complex connections between brain regions are referred to in relation to reward pathways?
Striatal, midbrain, limbic and prefrontal regions known as the mesocorticolimbic pathways
What pathway is made up of the striatal, midbrain, limbic and prefrontal regions?
Mesocorticolimbic
Why do we need to talk about “reward systems’ with caution?
- Some say the brain have evolved to express dedicated neural systems specifically for encoding reward or pleasure
- It is more likely that it has dedicated systems for motivating behaviour (which is positively reinforced) to survive (eg. feeding etc) and drugs interact and compromise these systems
Which brain area has elevated dopamine transmission when drugs such as amphetamine, cocaine, nicotine and morphine are taken?
Nucleus accumbens (a region of the ventral striatum heavily innervated by dopamine fibres)
What brain region has increased dopamine transmission when eating and having sex?
Nucleus accumbens
What receptors are critically involved in long-term potentiation?
NMDA and AMPA
What did Wise et al (1995) discover about dopamine levels in the nucleus accumbens in rats?
Dopamine levels in the nucleus accumbens increased during self-administered intravenous cocaine administration in rats
How did dopamine antagonists affect lever-pressing behaviour in rats?
Decreased lever-pressing behaviour and lesioning of the nucleus accumbens drastically reduce the rate of drug administration
What is Pargyline?
MAO inhibitor and prolongs the actions of 6-OHDA
How do dopamine antagonists affect the rewarding effects of drugs?
block the rewarding effects of drugs
How is dopamine related to Parkinsons disease?
People with Parkinson’s disease are known to have compromised levels of dopamine in the nucleus accumbens and mesollimbic pathways
What did patients of parkinson’s disease indicate about drugs of abuse?
They report blunted effects of stimulants, which supports the role of dopamine in the rewarding effects of drugs of abuse
What is Anhedonia?
Failure to experience rewarding stimuli
Lazenberge (2010) argued that, in addition to the dopamine system, the __________ _______ plays a critical role in mediating the experience of _________ evidenced by a voluminous body of ________-________ research.
- Serotonergic system
- pleasure
- depression-related
What did Self (2004) report about opiates and GABA?
Reported that opiates increase dopamine in part by removing the inhibitory influence of GABA neurons on dopamine-releasing cells
What is gabapentin?
A GABA agonist that has been found to reduce drinking, cravings, improve sleep and affect in participants with alcohol use disorder
What changes are associated with addiction?
a) synaptic plasticity
b) dendritic size and spines
c) changes in white and gray matter
d) up/down - regulation of receptors
e) changes in intracellular signalling pathways
What is long-term potentiation?
Efficiency of neurotransmission and plays a critical role in learning and memory
How does cocaine exposure effect long-term potentiation?
Has been found to increase LTP in the ventral tegmental area, lasting for days to months after cessation of treatment
How do opioids, cannabis and alcohol effect long-term potentiation?
Been found to elicit LTP in mesolimbic and mesocortical projection areas such as the nucleus accumbens, hippocampus, amygdala and prefrontal cortex
What happens to rats during exposure to psychostimulants?
Leads to sensitised locomotor responding to these drugs when rats are re-exposed to the drug weeks-to-months later
Repeated exposure to psychostimulants facilitates the acquisition of drug ______-________.
Self-administration
What is enhanced by sensitisation in animals?
Subsequent reinstatement of drug-seeking as well as the amount of work animals will produce to self-administer the drug
How does sensitisation affect dopamine neurons?
Enhances the excitability of dopamine neurons
How do amphetamines change dendrites?
Increased size of dendritic arbours
Increased number of spines
Elevates number of glutamatergic synapses
Where did Robinson et al (2001) find structural changes in neurons in rats that self-administered cocaine?
Neurons in the prefrontal cortex
What is gray matter?
Brain tissue containing cell bodies with unmyelinated axons
What has research found about gray matter volume and density in substance use disorders including alcohol, nicotine, meth and cocaine?
Reductions in gray matter volume in prefrontal regions and additional mesocorticolimbic structures
What have studies shown about gray matter and drug craving?
Drug craving was negatively associated with gray-matter in the insula, prefrontal cortex, amygdala, temporal cortex, occipital cortex, cerebellum and thalamus
What is white matter?
Tracks of myelinated axons
What did Rivkin et al (2008) report about children who were exposed to cocaine, tobacco, marijuana or alcohol in utero?
They had smaller head circumference and white and grey matter relative to children not exposed to these substances
What is CREB?
One of the most studied molecules targetted by cAMP
its a protein that plays a key role in learning and memory
What is correlated with an increase in phosphorylated CREB?
Diminished sensitivity to drug-induced reward
What did Eric Nestler postulate about CREB and drugs?
CREB provides a compensatory mechanism that responds to drugs and that could be linked wth tolerance and with symptoms of dysphoria and withdrawal, but could also play a more general role in signalling the response to stimuli with strong emotional salience
What activates CREB?
Morphine treatements in the nucleus accumbens
Stressors such as foot-shock and social stress
