Pathophysiology of Substance Abuse Flashcards
Define Abuse
self-administration of any drug in a culturally disapproved manner that causes adverse consequences
Define Addiction
a behavioral pattern of drug abuse characterized by compulsive use of the drug and strong tendency to relapse after discontinuation
Define Tolerance
state of physiologic adaptation to a drug such that higher than usual dosages are required to achieve the usual effect
Define Sensitization
increased response arising from chronic use of initial withdrawal
Define Physical Dependence
state of physiologic adaptation to chronic use of a drug such that abrupt reduction or cessation results in a characteristics abstinence or “withdrawal” syndrome
Define Psychological Dependence
Syndrome where one feels a strong urge or “craving” for the drug to achieve or maintain the altered mood or feeling state
Variables that influence the likelihood of a person becoming a drug abuser:
Cost and availability Purity Route of administration Speed of entry into brain Host and environment
Host variables that influence likelihood of becoming an abuser:
Hereditary (40-60%)
Teenagers/young adults
Early exposure
Mental Illness
Environment variables that influence likelihood of becoming an abuser:
Social setting and availability of reinforcers (peer pressure)
Community attitudes
Parental support
What is the major neuronal reward pathway?
Mesolimbic Dopaminergic Pathway
Mesolimbic Dopaminergic Pathway is constituted by
dopaminergic neurons linking the VTA (ventral tegmentum area) to the NA (nucleus accumbens) and the frontal cortex
What does the Mesolimbic Dopaminergic Pathway do?
Mediates the psychopharmacology of reward, whether for a natural high or a drug-induced high
“Pleasure center of the brain” with dopamine as the pleasure neurotransmitter
-Modulated by many natural substances to deliver normal reinforcement to adaptive behaviors and to produce “natural highs”, such as feelings of joy or accomplishments
Animal Model + Self-Stimulation
When an electrode is place in the NA, the rats press the bar repeatedly to receive the reward
Animal Model + Self-Administration
Rats will press the lever to inject a dose of cocaine to the NA but not other drugs
Addictive drugs + Reward Pathway
Drugs are positive reinforcers and increase the level of dopamine released in the mesolimbic dopaminergic pathway of the brain
Drugs of Abuse MOA
Stimulate mesolimbic dopaminergic fibers AND increased DA release in the NA or otherwise modulate the circuit to enhance reward and reinforcements
Brain’s Morphine/Heroin:
Endorphins
Brain’s Nicotine:
ACh
Drugs of Abuse in the Mesolimbic Pathway
Bypass the brain’s own neurotransmitters and directly stimulate the brain’s receptors in the reward system, causing dopamine release and a consequent “artificial high”
- No longer get a high from eating or drinking
***Reactive Reward Pathway
“Little devil that pushes you to do something bad”
- VTA to amygdala cause it to develop adaptive changes to remember the reward of drug abuse by the release of DA/NA from VTA to amygdala
- Signals the immediate prospect of either pleasure or pain and provides motivation and behavioral drive to achieve that pleasure or to avoid that pain
So what actually happens in the reactive reward pathway?
Memory of pleasure and memory of the environment cues associated with pleasurable experiences
Once reward learning occurs, connections go back to the VTA communicating whether anything relevant to a previous experienced pleasure has been detected
***Reflective Reward Pathway
“Willpower to resist”
Built over time based upon neurodevelopment, genetics and experiences
Projections from orbitofrontal cortex, ventromedial PFC, dorsolateral PFC
Projections from the orbitofrontal cortex (OFC) are involved in
regulating impulses
Projections from ventromedial PFC are involved in
regulating emotions
Projections from dorsolateral PFC are involved in
analyzing situations and regulating whether action should happen
First Time Abuser
Release of DA in the NA caused by VTA → euphoria (reflective)
VTA also sends DA to amygdala and it will learn to like it and want to repeat it
When cues are encountered, what happened?
the amygdala signals DA neurons in the VTA that something is good coming and this leads to DA release in the NA
What happens after DA release in the NA?
Triggers GABA-ergic input to the thalamus
Thalamus input to the PFC and unless the reflective reward system is activated leads to action such as drug seeking behavior
Will Power =
Reflective Reward System (PFC circuits)
- If this is low, the indiviudal may succumb to temptation
Acute Addiction:
Drug causes release of DA in the NA and positive reinforcement of drug-seeking behavior
Chronic Addiction
Continued drug use leads to adaptions of receptors and biochemical pathways
- Pharmacodynamics adaptions: receptor down-regulation
- Pharmacokinetics: stimulated metabolism and excretion
Short-Term Abstinence
Withdrawal symptoms begin (mainly physical)
Long-Term Abstinence
Physical addiction is gone, cravings still occur
Exposure to previous context of drug use can reactivate old memories
Treatment becomes life-long process to prevent relapse
