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25 Cards in this Set
- Front
- Back
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Tachyphylaxis
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Acute rapid tolerance built to a substance.
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Tolerance
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A given dose produces less of an effect.
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Physical dependence
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Altered phys state produced by repeated admin of a drug which necessitates the continued use of the drug to prevent withdrawal or abstinence syndrome.
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Is addiction the same as physical dependence?
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No
Addiction is a chronic relapsing brain disease characterized by compulsive drug seeking and use. |
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Cross-dependence/Cross-tolerance
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Abil of one drug to supp withdrawal produced by another and maintain physically dependent state.
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Mechanisms of physical dependence and tolerance
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Glial cells have a role (hyperalgesia-means increased sensitivity to pain)
Adaptive changes in intracellular second messengers also play a role. Change in receptor number or affinity - not really the case |
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Key NTs in substance abuse
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Dopamine, glutamate, endogenous opioids.
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Probably the most addictive drug...
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Cocaine.
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Main projection areas of drug addiction
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VTA, nucleus accumbens, prefrontal cortex. (cocaine specifically localizes to VTA and NA)
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Cocaine mech of action
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Blocks recycling/reuptake of DA in cleft so more is in the synapse to work on the receptors.
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Endogenous opioids
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Stimulate DA release
e.g. endorphins (released from anterior pituitary and hypothalamus). At low alcohol doses, their levels go up, but at higher doses, they go back down (graph looks like an arc) |
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Opioid antagonists -
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Naltrexone and nalmefene
(I think naloxone too) |
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Buprenorphine
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Potent and long-acting partial mu agonist and kappa antagonist. It dissociates very slowly from opioid receptors, so an overdose is difficult to tx.
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Subutex and suboxone tablets
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Subutex - buprenorphine hydrochloride
Suboxone - buprenoprhine hydrochloride and naloxone hydrochloride) "if injected, naloxone will block the effect of buprenorphine and can cause withdrawal." |
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Relapse due to...
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Stressors activate the mesocorticolimbic DA system and re-instate drug self-admin.
Vulnerability has genetic and env bases |
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3 stages of addiction in terms of gene txpn
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1 - acute drug effects
2 - transition to addiction 3 - end-stage addiction |
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More specific drug states combined with abstinence in terms of gene txpn
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Acute drug state - pt gets reinforcement and reward
(increase in mesolimbic dopaminergic and maybe serotoninergic) Chronic drug state - pt gets tolerance, sensitization, dependence (due to more cAMP) If pt does short term abstinence - withdrawal (increase in glutaminergic, noradrenergic, dopaminergic, serotoninergic, and increase in CRF [corticotropin releasing factor]) Long-term abstinence - pt gets cravings and stress-induced relapse (due to synaptic remodeling - after continuous glutamate and DA signals) |
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Main NT in nucleus accumbens
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glutamate
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Main NT in prefrontal cortex and VTA
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DA
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Why does stress trigger drug-seeking?
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Amygdala projects to VTA which projects to prefrontal cortex.
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Final common pathway in drug seeking
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Prefrontal cortex to NA to ventral pallidum
due to stress, drug-associated cue or the drug itself. |
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Acamprosate
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Inhibits glutamate signaling by competitive inhibition of NMDA receptors.
(similar efficacy as naltrexone in treating alcoholism) |
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Addiction shares mechanisms of neural plasticity along with...
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reward, learning, memory. (through dopamine and glutamate)
causes changes in dendritic spines. |
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Molecular mechanism of addiction
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Upreg of cAMP via CREB txpn factor. This leads to a change in gene exp and true synaptic changes (including post-synaptic density proteins)
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Neural circuitry
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Slide 25
Amydala (stress) or VTA to prefrontal cortex to NA to VP |
