Topic 20: Cocaine Systems Flashcards
What is cocaine use in the USA?
cocaine is the second most popular illicit drug in the USA
second only to cannabis
What is the history of cocaine and crack prosecutions?
in the USA the Anti-Drug Abuse act of 1986 established mandatory minimum sentencing for possession of cocaine and crack-cocaine
despite the fact that crack and powdered cocaine have the same active ingredients sentencing established a 100:1 disparity
many speculate this disparity contributed to racial bias in drug prosecutions
What is prenatal cocaine exposure?
rise in crack cocaine use during 80s and 90s lead to concerns about PCE
in utero exposure to crack-cocaine was correlated with: premature birth, lower birth weight, mental and physical defects
public opinion formed around the risks of PCE leading to prosecution of mothers who tested positive for cocaine or metabolites
What are the perceptions of prenatal cocaine exposure?
media reports of “crack babies” were highly sensational
experts predicted a “biological underclass” of delinquents affected by PCE
crack cocaine can be explicitly tested by the presence of methylecgonidine
What are the effects of prenatal cocaine exposure?
cocaine readily crosses the placental barrier
animal studies do not support long-term effects of PCE: studies support moderate decreases in learning in the presence of distractions
most described effects of PCE in humans can be attributed to confounding factors
prenatal nutrition, pre- and post-natal care, additional drug use (alcohol/tobacco), environmental risks, increased rates of STI
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
How is cocaine sympathomimetic?
cocaine elevates NE signaling at noradrenergic locations
cocaine exerts activating effects on the sympathetic nervous system
increased heart rate, vasoconstriction, hypertension, hyperthermia
many adverse effects of cocaine are due to sympathetic activation (stroke, heart failure, seizure, intracranial hemorrhage)
central noradrenergic effects contribute to the psychostimulant effects of cocaine
What are the dopaminergic effects?
dopamine plays a central role in the psychostimulant response to cocaine
two key pathways
nigrostriatal: substantia nigra to the striatum
mesolimbic: ventral tegmentum to nucleus accumbens
behavioral effects in rodents can be examined using microinjection and lesions
What is the nigrostriatal pathway in cocaine?
substantia nigra to the striatum
microinjection of cocaine into striatum elicits stereotyped behaviors
lesion with 6-OHDA antagonizes psychostimulant-induced stereotypes
What is the mesolimbic pathway in cocaine?
ventral tegmentum to nucleus accumbens
microinjection of cocaine into NAc elicits hyperactivity
lesion with 6-OHDA blunts psychostimulant-induced hyperactivity
lesion diminishes reinforcing effects of cocaine administration
however, microinjection does not readily lead to self-administration
How is the basal ganglia involved in the dopamine pathway and cocaine?
dopamine balances activity between the direct and indirect pathways
activation of nigrostriatal dopamine pathways promotes the direct pathway (D1 - excitatory) over the indirect pathway (D2 - inhibitory)
cocaine elevates DA in the striatum and drives locomotor activity (often purposeless)
What are the euphoric and reinforcing effects of cocaine in the dopamine pathway?
euphoric effects (subjective “high”) has been well studied by PET imaging: DAT occupancy by cocaine, D2R occupancy by DA
rate of onset of DAT occupancy correlates with intensity of euphoria: smoking > IV > intranasal»_space; oral
individuals with increased D2 receptor occupancy prior to cocaine administration have greater euphoric effects
What are the reinforcing effects of cocaine?
cocaine use in humans leads to addiction in 10-15% of users
recent animal work has challenged the strength of the reinforcing effects of cocaine
several studies have shown that given free choice rats will choose sweetened water over cocaine infusion
What is cocaine psychosis?
characterized by transient paranoid psychosis with delusions and hallucinations
common feature of chronic high-dose cocaine abuse (binge use): restricted to periods of drug use
not as well characterized as psychosis associated with amphetamines
occurs more frequently over time: result of sensitization to drug (increased effect over subsequent doses)
similar to psychosis in schizophrenia: sensitive to antipsychotics - mesolimbic DA
What are the characteristics of acute cocaine tolerance?
chronic cocaine infusion reduces the locomotor effects of a single cocaine injection (measured by simple locomotor tests)
What are the characteristics of chronic cocaine sensitization?
daily injection of cocaine results in increased stereotypic behaviors in rats over time (head bobbing, corner-to-corner motion, and vertical rearing/nose poking)
