Cocaine Systems Flashcards
what is the second most popular illicit drug in the USA and what is the first one?
cocaine; cannabis
how much kg of drug possession did it take for prosecution
1kg
what did this disparity contribute to
racial bias in drug prosecution
what is PCE
prenatal cocaine exposure
what was in utero exposure to crack-coaine correlate with
- premature birth
- lower birth rate
- mental and physical defects
crack cocaine be explicitly tested by what drug presence
methylecgonidine
fill in the blank: From 1980-89 studies showing effects of cocaine on fetal development has a ____ ___________________ _______ while those showing lack of effects had an____ ______________ ______
- 57% publication rate
- 11% publication rate
true or false: animal studies support long-term effects of PCE
false; but there is a moderate amount of support for a decrease in learning in the presence of distraction
Most described effects of PCE in humans can be attributed to confounding factors which are?
- Prenatal nutrition, pre- and post-natal care, additional drug use (alcohol/tobacco), environmental risks, increased rates of STI (incl. HIV and hepatitis)
- Child more likely to be exposed to maternal depression, domestic violence, ‘deadbeat’ parenting – all affect early childhood development
- Small increased risk of ADHD or increased impulsivity/distractibility
what does cocaine elevate the signalling of at the noradrenergic locations
NE
what are the many adverse effects of cocaine and what are they?
- sympathetic activation
- stroke, heart failure, seizure, intracranial hemorrhage
what are the two key pathways that dopamine plays a central role in
- nigrostriatal-> substantia nigra to the striatum
- mesolimbic-> ventral tegmentum to nucleus accumbens
what type of behaviours does SN to striatum elicit and what do lesions with 6-OHDA antagonize
- stereotyped behaviours
- psychostimulant-induced stereotypes
what does microinjection of cocaine in the VTA to NAc elicit and what does lesions do
- hyperactivity
- diminishes the reinforcing effects of cocaine administration
Take a look at slide 10
ye
how have euphoric effects been studied
- PET imaging
- DAT occupancy by cocaine
- D2R occupancy by DA
true or false: rate of onset correlates with intensity of euphoria
true; smoking-> IV-> intranasal-» oral
fill in the blank: individuals with increased _____ receptor occupancy before cocaine administration have greater euphoric effects
D2
true or false: cocaine in humans leads to addiction in 20-25% of users
false; 10-15%
what have several studies shown regarding the free choice rats have between sweetened water and cocaine
that rats will choose sweetened water over cocaine infusion
what is cocaine psychosis characterized by
transient paranoid psychosis with delusions and hallucinations
what is one one feature of cocaine psychosis and is it well characterized as psychosis associated with amphetamine
- common feature of chronic high-dose cocaine abuse (binge use)
- it is not well-characterized
true or false: cocaine psychosis occurs more frequently as a result of sensitization to the drug
true
true or false; cocaine psychosis is similar to psychosis in schizophrenia
true- sensitive to antipsychotics- mesolimbic DA
true or false: in chronic sensitization daily injection of cocaine results in increased stereotypic behaviours in rats over time (head bobbing, corner-to-corner motion, and vertical rearing/nose poking)
true
true or false: chronic cocaine infusion increases the locomotor effects of a single cocaine injection
false
what regulates overall rate of catecholamine synthesis in acute cocaine tolerance
TH
what does phosphorylation involve
- activity-dependent activation (CaM-Kinase phosphorylation)
- modulatory activation (PKC signalling
what does acute tolerance result from and what do presynaptic autoreceptors respond to
- results in large part from inhibition of dopamine biosynthesis
- responds to prolonged DA in the synapse to inhibit TH
what is chronic heavy cocaine use assoicated with
mild cognitive impairment -> verbal memory, attention and motor function-> correlated with gray and white matter abnormalities
what are the cardiotoxic effects of chronic use
arrhythmia, cardiac myopathy, myocardial infarct
what are the two administration-dependent effects
- intranasal-> perforation of the nasal septum
- smoking-> crack lung, scarring and damage to lung tissue due to vasoconstriction of vessels in the lung
what two receptor antagonists reduce the reinforcing effects of cocaine
D1 and D2
specific D3 antagonist or partial agonists decrease_ _____ or ______
SA; CPP
Look at slide 18 for human trials and take note of the words in bold
true or false: in animal and clinical trials cocaine vaccination reduces response to drug
true
true or false: reduces effects by altering craving or impulse to use
false; doe not alter
what does vaccine efficacy require
regular boosters as cocaine is not itself immunogenic- need to maintain high antibody levels
look at slide 11 and 12
what has been studied well using PET imaging
euphoric effects
- DAT occupancy by cocaine
- S2R occupancy by DA
true or false: rate of onset of DAT occupancy correlates with intensity of euphoria
true
what percentage of users of cocaine lead to addiction
10-15%
through several studies with rats, what has been shown
that the rat given free choice, will choose sweetened water of cocaine infusion
what is cocaine psychosis characterized by
by transient paranoid psychosis with delusions and hallucinations
what is the term for chronic high-dose cocaine abuse
binge use
what is cocaine psychosis similar to
psychosis in schizophrenia and is sensitive to antipsychotics– mesolimbic DA
what is seen in acute tolerance
there is inhibition of tyrosine hydroxylase (forms catecholamines) -> not able to create dopamine -> not as much as a high effect so keep taking cocaine to reach it
what is seen in chronic sensitization
daily injection results in increased stereotypic behaviours in rats over time
what happens in acute cocaine tolerance
phosphorylation
- Activity-dependent activation (CaM-kinase signalling)
- modulatory activation (PKC signalling)
what does acute tolerance result from
from inhibition of dopamine biosynthesis
-presynaptic autoreceptors responds to prolonged DA in the synapse to inhibit TH
look at slide 18 for adverse effects of cocaine use
have fun
look at slide 19 and 20 for addiction treatment and human trials
good luck
