neurobiology and neuropharmacology of substance use disorders Flashcards

1
Q

positive reinforcement vs negative reinforcement

A

positive reinforcement –> they feel good after, is “rewarding”; gives a “rush”

negative reinforcement –> the drug alleviates anxiety or depression or alleviates withdrawal syndrome

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2
Q

major opiates and their actions on a timeline

A

morphine, heroin, oxycodone, and fentanyl

initial N/V, rush(few minutes),

euphoria (1-2 hrs),

sedation/dissociation (2-4 hrs) and analgesia (2-4 hrs)

higher doses can cause respiratory depression, sedation, immune disturbances and constipation

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3
Q

5 target pathways of the drugs of abuse

  • 3 mediated by DA
  • 1 mediated by NE
  • 1 mediated by 5HT
A
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4
Q

dopamine pathway

increased DA leads to…

A

fibers project from the VTA to the nuc. accumbens and prefrontal cortex

(midbrain to forebrain)

**feedback control is provided by GABA neuron regulation

increased DA in the nuc accumbens leads to euphoria

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5
Q

enkephalins effect in the dopamine pathways

what do they inhbiit?

A

enkephalins elevate DA in the nucleus accumbens

Enkephalins, released from enkephalin neurons, enhance dopamine release from VTA dopamine neurons in the N. Accumbens by inhibiting GABA release. Also, enkephalins directly inhibit GABA neurons in N. Accumbens.

GABA turns off dopamine firing

**they inhibit activity of GABA neurons in the VTA and nuc accumbens so that dopamine neurons can remain active

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6
Q

target for opiates (morphine) in the dopamine pathway is on the

A

GABA neurons

inhibits gaba release so that dopamine release is enhanced

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7
Q

during opiate withdrawal,

A

DA pathways become less active; less DA release in Nuc. accumbens, PFC (loss of euphoria/reward feedback)

• NE release from locus ceruleus pathways to forebrain and spinal cord, normally reduced by acute opiate action, is increased; locus ceruleus neurons firing rate increased (anxiety)

NE pathway (lovus ceruleus) is activated

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8
Q

opiates effect on DA pathway vs NE pathways

A

activates DA pathways and reduces NE pathways

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9
Q

features of an opiate dependent state

A

reduced effect of all opiates (cross tolerance)

little cross tolerance to other centrally acting drugs

physical dependence - withdrawal syndrome after both discontinuation or administration of an antagonist (naloxone = trtmt drug)

**but it IS possible to be dependent on opioids and maintain normal life (fentanyl) = anesthesiologist occupational hazard!!!

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10
Q

opiate withdrawal timeline (morphine/heroin)

A

6-12 hrs: lacrimation, rhinorrhea, yawning, gooseflesh,

12-24 hrs: restless sleep

16-96 hrs: dilated pupils, gooseflesh, tremor, weakness, anorexia, nausea, vomiting, intestinal spasms (cramps), diarrhea, muscle and back pain, muscle spasms / jerks, CNS stimulation (ejaculation, orgasm), depression, weight loss, acid-base balance changes, dehydration and ketosis

Maximum symptoms at 48-72 hrs after last dose

Symptoms abate within 7 - 10 days

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11
Q

opiate withdrawal time course is more rapid/intense in _______ and slower, less intense in ______

A

more rapid/intense in meperidine dependence

slower, less intense in methadone dependence

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12
Q

opiate withdrawal in the newborn

A

Babies born to opiate-addicted mothers suffer withdrawal on delivery.

Symptoms include:

  • irritability,
  • excessive high pitched crying,
  • tremors,
  • violent sucking on fists,
  • hyperactive reflexes,
  • increased bowel activity,
  • vomiting, and fever.

treatment is small doses of opiates to wean baby off of it.

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13
Q

after initial detox, ______ is common, _____ continues for months or years, and ________ syndrome occurs

A

relapse is common

craving

conditioned withdrawal syndrome - induced by a return to an environment in which drugs have previously been used; shows all the features of opiate withdrawal

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14
Q

two opiate antagonists?

they can cause….

A

naloxone

naltrexone

withdrawal symptoms

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15
Q

compensatory changes that occur with opiate tolerance

A
  • µ opioid receptor are desensitized
  • little down regulation (little reduction in # of receptors)
  • neurons become less sensitive to drug

Compensatory changes:

  • signal transduction pathways modified
  • patterns of gene expression altered

***withdrawal effects are opposite to acute effects of the drug!!

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16
Q

what site in brain is related to the behavioral reinforcement “the high”?

A

DA pathway (VTA –> nuc accumbens)

17
Q

what area of brain is related to the cognitive aspects of dependence (drug seeking behaviors)?

A

pre-frontal cortex

18
Q

what area of brain is related to the pain and the autonomic symptoms of withdrawal?

A

peri-aqueductal gray region (PAG) and

locus coeruleus

19
Q

what area of brain is related to the anxiety, fear and dysphoria of opiate withdrawal?

A

VTA - nuc accumbens and amygdala

20
Q

which is not a characteristic feature of withdrawal from chronic opiate use?

back spasms

ejaculation/orgasm

intestinal cramps

tonic-clonic convulsions

weightloss, dehydration and ketosis

A

t-c convulsions

21
Q

prescribed opiates like oxycodone, hydrocodone, and methadone all act through the ___

A

µ-type opioid receptors.

just like morphine

22
Q

which prescribed opiate has highest rate of rise in deaths?

A

methadone

23
Q

ethanol mechanism in neuronal pathways

A

inhibition of glutamate (NMDA)-activated cation currents –>reduces neuronal excitability

potentiation of GABAA receptor activated chloride currents –> facilitates GABA-induced hyperpolarization, reduces excitability

24
Q

cocaine inhibits _______

A

DA transporter, and NET and SERT

25
Q

amphetamines releases which transmitters?

A

DA, NE, 5HT

26
Q

amphetamines mechanism at DAT

A

Amphetamine:

enters via DAT

displaces DA from vesicles

inhibits MAO

inhibits VMAT

(in nuc accumbens)

27
Q

When circuits are balanced (A) there is appropriate inhibitory control and decision making. During addiction (B), enhanced expectation value of the drug in the reward, motivation and memory circuits overcomes the control circuit, favoring a positive feed-back loop initiated by the consumption of drug.

A
28
Q

raphe nucleus pathway uses which transmitter?

locus ceruleus uses which transmitter?

A

RN –> 5HT

LC –> NE

29
Q

nucleus accumbens, and ventral striatum are all part of a network of structures called the _______ that is involved in -____________ behaviors

A

extended amygdala

reward and addictive