Substance use disorders Flashcards
What does striatum consist of?
Dorsal striatum?
Ventral striatum?
Striatum = caudate, putamen, and NA
Dorsal striatum = corpus striatum = caudate + putamen
Ventral striatum = NA
BG –> thalamus –> ???
Cortex involved in action, such as motor cortex and premotor association cortex
What parts of cortex project to NA?
PFC, amygdala, and hippocampus
What type of cell makes up the striatum?
Medium spiny neuron. 1 cell has 10,000 inputs. Integrates glutamatergic cortical info and DA info from midbrain. GABAergic.
Reinforcement
Outcome of a behavior increases likelihood that behavior will be repeated. Negative reinforcement ex: rat presses lever to avoid shock
Reward
Subjective emotional experience (pleasure, euphoria, hedonia) that accompanies positive reinforcement
Impulsive behavior
What is a chemical sign of impulsivity?
Tendency to consistently choose immediate reinforcement, and impairment in ability to inhibit a course of action once initiated.
•Inheritance of impulsivity is marked by low levels of serotonin metabolites.
Compulsive behavior
Perseveration in behavioral strategy even in face of unsuccessful or adverse outcomes.
Mesolimbic DA system
Highly involved in reward. VTA → NA mediates motor effort to obtaining wanted goals. Blocking DA receptors w/ drugs blunts the brain-stimulation reward in rats. More stimulation is required.
Reward error prediction hypothesis
DA is important for learning about rewards. Firing of DA neurons occurs:
•The 1st time the organisms experiences a new primary reward
•When observing stimuli that reliably predict expected reward
•When a previously experienced reward is better than predicted
•DA neurons fire in response to reward early in training. Once trained, DA neurons fire in response to reward-predicting stimulus, but not the reward itself.
•DA released if reward comes earlier or later than expected. Learning. No release if reward comes at the expected time.
Incentive-sensitization hypothesis
Drug use causes long-lasting SENSITIZATION of DA’s ability to produce drug WANTING, even while drug liking may be decreasing.
Reward-error prediction hypothesis
Enhanced DA release during drug taking produces a condition in which all stimuli are experienced as BETTER THAN EXPECTED. This theory does not require drug to produce state of euphoria.
Impulsivity occurs w/ impairment of what?
PFC
What part of brain controls compulsive behavior?
Compulsivity occurs due to shift from PFC-NA motor circuits to an emphasis on dorsal striatal control. Dorsal striatum controls habits.
Cycle of addiction
Preoccupation / anticipation → binge / intoxication → withdrawal / negative effects
Repeat
Wernicke-Korsakoff Syndrome
Encephalopathy due to thiamine deficiency; early onset dementia w/ inability to form new memories. Px may be acutely confused. Macrosidic anemia due to low vit B12 and folate
•Tx – Give thiamine before giving glucose.
What reverses opioid intoxication?
Naloxone
Withdrawal from which 2 drugs can be lethal?
Alcohol and benzos
Common alcohol withdrawal sxs
Danger sxs
Time course
Common (same as benzos) - anxiety, nausea, tremors, sleeplessness, restlessness, sweating, headaches, rapid pulse, HTN
Dangerous sxs - psychosis, delirium, seizures
Time - common sxs stop after 3-4 days. DT’s may last 10+ days.
Common benzo withdrawal sxs
Dangerous sx
Common (same as alcohol) - anxiety, nausea, tremors, sleeplessness, restlessness, sweating, headaches, rapid pulse, HTN
Dangerous sx - seizures
Common opioid withdrawal sxs
Dangerous sxs
Common - Nausea, vomiting, craving, rhinorrhea, diarrhea, tearing, muscle aches / cramps, goosebumps, dilated pupils
Dangerous - dehydration from diarrhea / vomiting
Common stimulant withdrawal sxs
Tired, prolonged sleeping, amotivational, depressed, overeating, and craving
Treating alcohol withdrawal
Make pxs comfortable and avoid seizures, HTN, and delirium. Use of benzos help offset the unopposed opponent process of decreased GABA and increased glutamate function. Anticonvulsants such as gabapentin also modulates glutamate function.
Treating benzo withdrawal
Switch to long-acting benzo and taper
Treating opioid withdrawal
Buprenorphine, methodone, clonidine / benzo combo, intense psychosocial support
Treating stimulant withdrawal
abstinence and social support
Treating alcoholism
- Abstinence is most risk-free approach
- CBT – learn to avoid stimuli that remind them of drugs / alcohol and deal w/ anger / neg affective states that lead to relapse. Choose positive habits to replace negative habits.
- Relapse prevention therapy, motivational enhancement, and 12 step therapy all reduce drinking by 80% one year after therapy.
- Naltrexone blocks release of opioids, meaning a slip to use alcohol is less likely to lead to full blown relapse and craving are lessened. Interferes w/ positive reinforcement of alcohol.
- Acamprosate – has effects on both GABA and glutamate. May decrease DA release in NA in response to alcohol, decreasing reinforcing effects.
- Disulfiram – antagonizes aldehyde dehydrogenase → toxic build up of aldehyde after alcohol consumption → severe nausea and pain. Risk of cardiorespiratory collapse, so only use in very motivated pxs.
How does naltrexone aid in treating alcoholism?
Naltrexone blocks release of opioids, meaning a slip to use alcohol is less likely to lead to full blown relapse and craving are lessened. Interferes w/ positive reinforcement of alcohol.
How does acamprosite aid in treating alcoholism?
Acamprosate has effects on both GABA and glutamate. May decrease DA release in NA in response to alcohol, decreasing reinforcing effects.
