drug addiction exam 2 Study Guide Questions

why can different drugs produce similar effects even when the drug action is different?

the drugs are working on the same neural circuit

why can different drugs produce similar effects even when the drug action is the same?

the drugs are working on different neural circuits

Using the pharmacology method for grouping psychoactive drugs recall the drug effects and the site of action of psychstimulants, hallucinogens (i.e., psychedelics), and cannabinoid.

Cocaine- passes through cell membranes in the brain and acts by binding to dopamine transporter on presynaptic membrane. Blocks the normal reuptake of dopamine from the synaptic gap, resulting in prolonged dopamine activity on postsynaptic receptors. This causes a psycho-stimulating and reinforcing effect

What adaptations (changes in physiology) occur AT THE SITE OF ACTION of a drug with repeated drug use. What is the consequence of each adaptation on the drug effect?

The first is the downregulation of receptors. Repeated drug use may cause the body to produce fewer receptors or make the existing receptors less sensitive. The consequence of downregulation is that the drug becomes less effective at producing its desired effects because there are fewer or less sensitive receptors for it to bind to. Note that if the drug blocks a transporter, the body would produce more transporters in response to clearing out the toxic neurotransmitter to the neuron (upregulation of transporters), which produces less of an effect due to the faster clearing of neurotransmitters from the synaptic cleft.

The second is upregulation of enzymes. If a drug is repeatedly used, the body may produce more of the enzymes that break down the drug. The consequence of upregulation is that the drug is metabolized more quickly, so its effects are shorter-lived and less intense.

The third is changes in ion channels. Repeated drug use can cause changes in ion channel function, such as making the channels less responsive or less likely to open. The consequence of these changes is that the drug becomes less effective at producing its desired effects because it has a harder time affecting the ion channels.

The fourth is changes in intracellular signaling pathways. Repeated drug use can cause changes in these pathways, such as making them less responsive or altering the proteins involved in the pathways. The consequence of these changes is that the drug becomes less effective at producing its desired effects because the signaling pathways it affects are altered.

How might these PHYSIOLOGICAL adaptation underlie some changes associated with addictions (i.e., substance use disorder)?

Due to these physiological adaptions lessening the effects of the drug, drug users would tend to seek a higher dose of the drug to feel the same feeling of euphoria when they first took the drug, which contributes to addiction of the drug.

What 3 physiological processes did we discuss in class as physiological processes important for neuroplasticity?

These 3 physiological processes also allow for neural adaptations. But the physiological processes are less well understood at this time than those described in a.i above

The three physiological processes are homeostasis, stimulus amplification and neural remodeling that are important to neuroplasticity

homeostasis = plays an important role in neuroplasticity because it regulates the balance between the excitatory and inhibitory signals in the brain.

stimulus amplification = allows the brain to adapt to changing environments and experiences.

neural remodeling = essential for neuroplasticity because it allows the brain to optimize its neural circuits based on experience and learning

What is the relationship between genes, hormones, neurons, environmental stimuli on drug related behaviors and mental processes including SUD ('addiction').

How might these relationships help use to understand individual differences in addictions (i.e., substance use disorder)?

Drug/context/experience can have direct effect on neural circuit

Essentially all of these affect one another and can also affect individually

Opponent process theory: who developed it? when? what does the theory predict about brain and behavior adaptations to drug use? What symptoms of substance use disorder (as currently defined) seem to be explained by this theory?

developed by Richard Solomon and George Koob in the 1980s and this theory predicts that SUD is a learned homeostatic correction in response to repeated drug use; essentially, it is an anticipated response by the brain to change the drug. This theory explains tolerance and dependence in SUD.

Incentive sensitization: who developed it? when? what does the theory predict about brain and behavior adaptations to drug use? What symptoms of substance use disorder (as currently defined) seem to be explained by this theory?

developed by Dr Kent Berridge and Dr. Terry Robinson in 1993. This theory suggests that SUD is a learned association between the drug effects to drug-context and cues (external or internal cues and context). This theory explains the long term effects of addiction such as craving due to motivation due to stimulus amplification.

Stimulus-Response theory: who developed it? when? what does the theory predict about brain and behavior adaptations to drug use? What symptoms of substance use disorder (as currently defined) seem to be explained by this theory?

developed by Dr Evertt and Robins in 2005. This theory suggests that SUD is a learned habit due to changes in the reward pathway and induced by neural adaptations, resulting in the persistence and inflexibility of the drug taking behavior. This explains the long term effects of addiction such as craving due to it being a habit

Allostasis theory: who developed it? when? what does the theory predict about brain and behavior adaptations to drug use? What symptoms of substance use disorder (as currently defined) seem to be explained by this theory?

(Koob & Le Moal, 2001)

SUD is a change in physiological steady state.

In order to feel good, need more rewards/stronger stimulus to hit baseline of “good”

Explains concept of motivational toxicity or the “dark side of addiction” (During abstinence, ppl have low motivation for things except finding their drug.)

Allostasis developed from homeostasis

cocaine usual routes of administration

IV, inhalation, snorted, oral, or local

cocaine half life

30-90 minutes (0.5-1.5 hrs)

metabolism of cocaine and routes of elimination

Metabolites excreted slowly (days to week) and "depot" in hair as benzoylecgonine and ecgonine (inactive) or as cocaethylene (active, 2 to 2.5hrs half life) if metabolized in presence of alcohol.

Drug Actions of Cocaine

1. Physically blocks transporter opening, and holds it in position so it cannot transport neurotransmitters. Leads to increased availability of DA, NE, serotonin, therefore INDIRECT AGONISTS

2. Disrupts action potentials

action on dopamine underlies the desired effects

Stimulating (locomotor), exciting (hedonic) and reinforcing and addiction effects are best predicted from dopamine transporter action

Specifically, dopamine in mesolimbic/mesocortical dopamine pathway

receptors, enzymes, and transporters associated with cocaine

dopamine transporter (DAT)

cocaine has similar effects on/blocks norepinephine and serotonin transporters as well

Desired effects of cocaine

Stimulating, exciting/euphoric, and reinforcing effects result from its action as an indirect agonist, pain inhibiting

side effects of cocaine

Increase in mental awareness, alertness, feelings of pleasure and euphoria, rapid heartbeat

undesired cocaine effects

Adverse cardiovascular and respiratory effects result from its action as a Na+ channel blocker

pharmacokinetics of cocaine

Absorption can be very fast for cocaine HCl or crack depending on route of administration

IV/inhalation: peak blood levels in 5 min

snorted/oral: peak blood levels in 1 hour

Local: minutes

metabolism of cocaine is

rapid (half life is usually 30 min-1.5hrs)

Metabolites excreted slowly (days/week) and can depot in hair

Benzoylecgonine and ecgonine (inactive) or

Cocaethylene (ACTIVE, 2-2.5 hour half life) if metabolized in the presence of alcohol; use has declined over the years.

Cocaine allows for ppl to sober up from alcohol, so for some, they take cocaine before driving and drive better.

cocaine target

Dopamine, norepheniphrine and serotonin transporters

Voltage gated Sodium channels

cocaine proposed site of action

Physically block the transporter opening and holds it in position so it cannot transport neurotransmitters, leading to increased availability of DA, NE and serotonin (indirect agaonists)

Disrupts action potentials

overview of the research paper question

Physically block the transporter opening and holds it in position so it cannot transport neurotransmitters, leading to increased availability of DA, NE and serotonin (indirect agaonists)

Disrupts action potentials

research paper results

Wanting has an increased correlation with dependant and lifetime cocaine use?

Regular smoking increases cocaine dependance more than stimulants

There is no significant difference in liking and wanting in ADHD

Repeated exposure to cocaine decreases pleasure of taking cocaine