Chapter 12: Cocaine and Amphetamines Flashcards
cocaethylene
Metabolite formed from the interaction of cocaine and alcohol. It produces biological effects similar to those of cocaine but has a longer half life.
cocaine binges
Periods of cocaine use lasting hours or days with little or no sleep.
contingency management program
Type of addiction treatment program in which the client’s drug taking is monitored by regular urine testing and abstinence is reinforced with vouchers redeemable locally for consumer products or services.
crack
Form of cocaine made by adding baking soda to a solution of cocaine HCl, heating the mixture, and drying the solid.
drug-seeking behavior
Performance of an operant response such as a lever-press or a nose-poke with the expectation of receiving delivery of a drug dose.
expression
Process that leads to manifestation of a sensitized response and that requires enhanced reactivity of DA nerve terminals in the nucleus accumbens.
focused stereotypies
Behaviors produced by high doses of psychostimulants (e.g., cocaine and amphetamine) and characterized by repetitive and aimless movement.
freebasing
Smoking the freebase form of cocaine obtained by dissolving cocaine HCl in water, adding an alkaline solution, and then extracting with an organic solvent.
incubation
Time-dependent increase in drug craving and drug seeking behavior during abstinence.
induction
- Increase in liver enzymes specific for drug metabolism in response to repeated drug use. 2. Process that establishes psychostimulant sensitization by activating glutamate NMDA receptors and, in some cases, D1 receptors.
mephedrone
Cathinone derivative (4-methylmethcathinone) that is an emerging abused stimulant drug. It is a member of a group of compounds sometimes called “legal highs.”
narcolepsy
Sleep disorder characterized by repeated bouts of extreme sleepiness during the daytime. Symptoms include sudden cataplexy, sleep paralysis, and dream-like hallucinations.
psychosocial treatment programs
Counseling programs that involve educating the user, promoting behavioral change and alleviating problems caused by drug use.
relapse prevention therapy
Treatment program for drug abusers that teaches an individual how to avoid and cope with high-risk situations.
sympathomimetic
Substance that produces symptoms of sympathetic nervous system activation.
psychomotor stimulants
marked sensorimotor activation; increase alertness, heighten arousal, and cause behavioral excitement
naturally occurring form of cocaine
alkaloidal cocaine
two synthetic forms of cocaine
WIN 35,428 (CFT) and RTI-55; more potent than cocaine
how cocaine is extracted
coca leaves contain between .6% and 1.8% cocaine. Initial extraction of the leaves results in coca paste containing about 80% cocaine. The alkaloid is then converted to hydrochloride (HCl) salt and is crystalized.
two ways cocaine is transformed into cocaine freebase
- freebasing
2. crack
is smoking crack the same as doing cocaine?
the heat in smoking crack produces unique chemical products that can be detected in the urine
how cocaine exerts its effects
is lipophilic (fat soluble) and readily passes through the BBB; once absorbed into circulation, it is rapidly broken down by enzymes found in the blood stream and liver
how long do cocaine’s effects last?
half life is .5-1.5 hours, but the high only lasts about 30 minutes
benzolecgonine
major metabolite in cocaine; can be detected in urine for several days following last dose
mechanisms of action for cocaine
blocks the reuptake of three monoamine neurotransmitters (DA, NE, 5-HT); these neurotransmitters are cleared from the synaptic cleft by membrane proteins called transporters. cocaine binds to the transporters to inhibit their function which leads to increased neurotransmitter levels in the synaptic cleft and an increase in transmission at the affected synapses.
what neurotransmitter transporter does cocaine bind most strongly with?
5-HT, then DA, then NE
what does the blockage of DA reuptake do?
important for cocain’s stimulating, reinforcing, and addictive properties
what does cocaine do at high concentrations?
also inhibits voltage-gated sodium (Na+) channels in nerve cell axons which causes a block in nerve cell conduction. Thus it can be used as a local anesthetic by preventing transmission of nerve signals along sensory nerves
behavioral effects of cocaine
high, feelings of exhilaration and euphoria, sense of well-being, alertness, heightened energy, diminished fatigue, self-confidence, a rush, increases sociability and talkativeness, heightened sexual interest, increase in aggressive behavior, increased behavioral activation
physiological consequences of cocaine
increased heart rate, vasoconstriction, hypertension (increased blood pressure), hyperthermia (elevated body temperature), seizures, heart failure, stroke, intracranial hemorrhage
what happens if you create a neurotoxic lesion in the nucleus accumbens?
prevents psychostimulant induced locomotion
what happens if you create a neurotoxic lesion in the striatum?
antagonize the stereotypes associated with higher drug doses
what does the mesolimibic DA to the nucleus accumbens play a role in?
the reinforcing effects
mutant mice lacking DA transporter DAT
fail to show hyperactivity following psychostimulant use
drug seeking behavior
performance of an operant response such as a lever-press or a nose-poke with the expectation of receiving delivery of a drug dose
what does the nucleus accumbens also seem to play a role in?
the urge to take cocaine in dependent users who are attempting to maintain abstinence
what causes the high?
- the drug binds to DAT and prevents DA reuptake; once a certain level of DAT occupancy (40-60%) is attained following cocaine or methyphenidate administration, the subject may experience a high; injection/smoking quickly blocks DAT and thus creates a high
- baseline level of DA activity in the mesolimbic pathway
DA receptors types
D1-D5; D1 and D5 are the D1-like family; D2, D3, D4 are the D2-like family
D1 receptors
locomotor-stimulating effects; D1 knockout mice do not self-administer
D2 receptors
mice lacking D2 self-administer cocaine
D3
present in the mesolimbic DA areas such as the nucleus accumbens; rewarding and reinforcing effects
what protects against long-term abuse of cocaine?
a strong anxiety response, unavailability of the drug, the cost, social and legal consequences, fear of losing control,
what percentage of users abuse it?
10-15% of initial intranasal users eventually become abusers
abstinence syndrome following a cocaine binge
crash; depressed mood; exhaustion; anhedonia, lack of energy, anxiety, craving,
brain abnormalities in cocaine dependent users?
abnormal prefrontal cortical functioning that is manifested as deficits in inhibitory control and in monitoring and evaluating consequences of their behavior
brain activity when presented with drug related stimuli
DA release in dorsal striatum (caudate and putamen); the midbrain-striatal DA pathway is part of a larger circuit that is activated when cocaine users experience craving
transition to compulsive use
longer periods of access to cocaine can lead to an escalation of intake that down-regulates the reward circuit. This presumably makes the cocaine less rewarding and thus supports further increases in drug consumption
what is addiction a result of?
a combination of prolonged exposure to the drug, which can be seen from the fact that changes in behavior occurred only after many self-administration sessions and factors that lead to differential vulnerability among individuals
sensitization phases
- induction
- expression
during the period between these two phases sensitization can actually increase in strength as the result of ongoing neurochemical changes in the brain
what tends to show tolerance over time?
cocaine’s euphoric effects
neural mechanisms of sensitization
DA activity in the VTA plays an important role in locomotor sensitization; medial prefrontal cortex which sends a glutamatergic projection to the VTA and the NaCC
neural mechanisms of tolerance
baseline level of D2 receptor binding is reduce in cocaine-dependent subjects; the DA system is less responsive to DA reuptake blockade which contributes to behavioral tolerance
problems associated with repeated cocaine use?
stroke or seizure, abnormalities in gray and white matter in cerebral cortex, decreased volume of some cortical regions and striatum, impairment in cognitive functions, including verbal memory, attention and motor function, chest pains, irregular heart rate, damaged heart muscle, heart attack, perforation of the nasal septum, panic attacks, paranoid psychosis with delusions and hallucinations
using antabuse (disulfiram) for the treatment of cocaine abuse
inhibits the enzyme aldehyde dehydrogenase and inhibits dopamine beta-hydrozylase (DBH) the enzyme that synthesizes NE from DA and inhibits esterases that are involved in the breakdown of cocaine
cocaine vaccine
antibodies bind to cocaine molecules or may have catalytic activity that actually breaks down cocaine in the bloodstream
amphetamines
synthetic psychostimulants available in two forms, L-amphetamine and D-amphetamine
how to take amphetamines?
typically either orally, IV, or subcutaneous injection; takes up to 30 minutes for behavioral effects after a typical oral dose of 5-15 mg
is methamphetamine the same?
it is a more potent form
speedball
to moderate the extreme stimulatory effect of IV amphetamine or meth by combining it with heroin
how are amphetamines/ meth metabolized?
in the liver and excreted in the urine; half life ranges from 7 to 30 hours for amphetamine and 10 hours for meth
mechanisms of action of meth and amphetamine
are indirect agonists of the catecholaminergic systems and release catecholamines from nerve terminals. at very high doses they inhibit catecholamine metabolism by monoamine oxidase;
catecholamine release in amphetamines/ meth
- cause DA molecules to be released from inside the vesicles into the cyctoplasm of the nerve terminal; then DA molecules are transported outside the terminal by a reversal of the DAT, the result is a massive increase in synaptic DA concentrations and an association stimulation of DA transmission; DAT reversal is facilitated by an activation of protein kinase C and calcium/ calmodulin kinase II resulting in phosphorylation of the transporter
- NE releasing effects of amphetamines occur in the brain and the sympathetic nervous system
behavioral effects of amphetamine
heightened alertness, increased confidence, feelings of exhilaration, reduced fatigue, generalized sense of well-being, improved performance on simple, repetitive psychomotor tasks, delay in sleep onset, reduction in REM, enhanced athletic performance, psychotic reactions, neurotoxicity
uses of amphetamine
narcolepsy, ADHD, suppression of appetite and weight reduction (antiobesity treatment);
withdrawal of amphetamine
depressed mood, increased anxiety, sleep disturbances, cognitive deficits, craving, agitated behavior, reduced energy, increased appetite; may take up to several weeks to subside
are men more likely to become dependent on meth?
no
Psychotic reactions to amphetamine
visual/auditory hallucinations, behavioral disorganization, paranoid state with delusions of persecution, parasitic skin infestation; occurs only after a chronic abuse pattern
risk factors for psychotic reactions
long history of use, high doses, dependence, a preexisting history of psychotic symptoms
neurotoxicity
long lasting reductions in levels of DA, tyrosine hydrozylase (enzyme in DA synthesis), DAT in the striatum, damage to DA axons and terminals, damage to serotenergic fibers in the neucortex, hippocampus, and striatum
what likely causes neurotoxicity?
oxidative stress (cellular stress due to increased production of oxygen containing free radicals), excitotoxicity, neuroinflamation, and mitochondrial dysfunction
loss of striatal DA
could potentially predispose heavy users to an early onset of Parkinson’s disease
physical health and amphetamine use
cardiovascular problems, elevated heart rate and blood pressure, atherosclerosis, myocardial infarction, increased risk of stroke, increased mortality rate, premature aging
info about mephedrone
snorted, causes euphoria and energy, inhibits 5-HT and DA uptake and increases extracellular levels of both in the NaCC, sympathomimetic toxicity, agitation, seizures, death; DA and 5-HT toxicity
