Addiction Flashcards
(35 cards)
What is a drug?
A drug is any substance that can have an effect on a biological system.
What is addiction?
Have to have the drug, and cannot function without it. Once we have developed a dependency, it is a chronic condition - can never be cured, and becomes a constant battle to remain off the drug.
What are substance use disorders in DSM 5?
Impaired control, social impairment, risky use, and pharmacological criteria.
What is impaired control?
The individual may take the substance in larger amounts/over a longer period of time that was originally intended. May express a persistent desire to cut down/regulate use, but be unsuccessful. May spend a great deal of time obtaining the substance. Craving is most likely when in an environment when the drug was previously obtained/used.
What is social impairment?
Recurrent substance use may result in a failure to fulfil major role obligations at work, school or home. Continue substance use despite having persistent social/interpersonal problems. Activities may be given up and the individual may withdraw from activities to use the substance.
What is risky use of the substance?
Recurrent substance use in situations in which it is physically hazardous. May continue substance use despite recurrent physical or psychological problems.
What is tolerance?
Signaled by requiring a markedly increased dose of the substance to achieve the desired effect. Degree to which tolerance develops varies greatly across different individuals. Tolerance is not necessary for the person to be considered as having a substance use disorder.
What is withdrawal?
A syndrome that occurs when blood or tissue concentrations of a substance decline in an individual who had maintained prolonged heavy use of the substance. Our body attempts to adapt & get used to the substance - because of this adaption, it creates withdrawal symptoms. This is the opposite symptoms of the effect the drug has. This is not necessary for a diagnosis of a substance use disorder.
Why have substance use disorders been placed on a continuum?
Substance use disorders occur in a broad range of severity, from mild to severe, with severity based on the number of symptom criteria endorsed. Mild disorder is suggested by the presence of 2-3 symptoms, moderate by 4-5 symptoms, severe by 6+ symptoms.
What is the mesocorticolimbic dopamine system?
Dopamine neurons projecting from ventral segmental area (VTA) to nucleus accumbens (NAc) and prefrontal cortex (PFC). Natural reinforcers (e.g. food & sex) increase extracellular dopamine in the nucleus accumbens. All known addictive drugs also activate this system. Have large release of dopamine (10x the amount released for a natural pleasure) - the reinforcing aspect is a need for it again, due to the magnitude of reinforcement. Therefore very easy for us to get addicted.
What are direct mechanisms by which addictive drugs increase dopamine availability/release in Nucleus Accumbens (NAc)?
Cocaine/amphetamine - increase availability at synapse by blocking or reversing dopamine transporters. If block dopamine transporter you don’t do the reuptake, and therefore have more dopamine in the synapse to act on the postsynaptic cell.
Nicotine - direct excitation of VTA neurones by action at nicotinic receptors.
What are indirect mechanisms by which addictive drugs increase dopamine availability/release in Nucleus Accumbens (NAc)?
Opioids/Cannabinoids - action at opioid or cannabinoid receptors indirectly leads to modulation of VTA activity. e.g. inhibition of GABAergic projections onto VTA neurons allows them o fire resulting in increase in DA release.
What is associative learning?
“Cells that fire together wire together” (D.O.Hebb). Sensory information: people, places, emotions etc present at the time when DA release occurs will become associated with reward (salience). Coincident firing in NAc will induce LTP & strengthening of synaptic connections. Reward associated cues will trigger reward seeking behaviour & pause problems associated with relapse.
How does dopamine enhance LTP?
Synaptic re-modelling - increases spines & dendritic branching. Long-term molecular & cellular changes. Memories in these pathways may trigger relapse years later.
How is the frontal system dysfunctional in chronic substance abuse?
PET study showing reduced glucose metabolism in brain of a cocaine addict. Hypoactivity in these brain areas may underlie some of the behaviours associated with addiction - loss of motivational control and compulsive drug taking, loss of inhibitory control & inability to restrain when exposed to drugs.
What are binding sites of cocaine following acute administration?
Striatum contains the nucleus accumbent. The brain quickly uptakes the substance, and subsequently feels pleasure quickly afterwards.
How do we know this pathway is involved in reward?
Damage to the nucleus accumbens decreases self-administration of heroin. Mesocorticolimbic pathway needed for drug to have a rewarding effect.
What are psychomotor stimulants?
Cocaine and amphetamines. Potentiate monoaminergic transmission by inhibition of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) transporters. Cocaine blocks & inhibits transporter to prolong pool of extracellular DA. Amphetamine reverses transporter to increase extracellular DA levels. Action at dopamine transporter (DAT) most directly related to reinforcing effects.
What have animal studies found about psychomotor stimulants?
Subjective effects such as feelings of euphoria are probably mediated by action of drugs at other sites. In animal studies: DAT transporter knockouts still show some behavioural response to cocaine. Only triple knockout (DAT, SERT and NET) show no drug action.
What are opitates?
e.g. morphine & heroin. Act as endogenous opioid receptors. Inhibitory - decrease adenylyl cyclase activity, lead to open K+ channels and close Na+ channels. Subjective effects: Euphoria and intense rush with heroin compared to morphine due to route of administration and entry to brain (seconds vs minutes). Relaxing effects: inhibition of Noradrenergic pathways.
How do opiates impact on the function of the Dopaminergic reward pathways?
Reward & reinforcement by: Disinhibition of DA neurons in VTA (DA neurons fire tonically but are inhibited by GABA interneurons - μ receptor activation on GABA neurons inhibits them from firing - relieving inhibition of DA neurons.
AND
Action at opiate receptors in the NAc - independent of DA release.
What is the effect of alcohol?
Effects depend on ability to metabolise alcohol, & how much you have on board. Is a GABA a agonist (inhibitory) and NMDA antagonist (blocks excitation). Has effect on the cerebellum - so we lose coordination & may become sedated.
What are subject effects of alcohol?
Low doses of alcohol lead to mild euphoria & anxiolytic effects. Higher doses lead to poor coordination, amnesia, and sedation. Chronic alcoholism leads to Korsakoff’s Amnesia (inability to form new memories (anterograde amnesia). Not due to specific affect of alcohol, but the malnutrition caused by the consumption of alcohol (e.g. lack of nutrients)).
What effects does alcohol have on reward circuitry?
Alcohol leads to increased dopamine release in NAc - NMDA antagonism of cortical inputs to VTA may lead to increased dopamine release in NAc.
Suppression of cortical output leads to no activation of GABA interneuron, which leads to DA neurons being disinhibited in VTA and become able to fire.
