Exam 3 - Part 2 Flashcards
Cocaine administration
cocaine HCL can be taken orally, intranasally, by IV injection; can be smoked by freebasing and crack
Cocaine absorption
readily crosses BBB, producing a high; half life of 0.5-1.5 hrs and high lasts about 30 minutes
Benzoylecgonine
primary cocaine metabolite
Cocaethylene
produced by alcohol interactions with cocaine, has a longer half-life
Cocaine mechanism of action
reuptake inhibition that is strongest at DAT but also binds NET, SERT
Cocaine reinforcement without functioning DATs
through alpha1 NE receptors and ACh; DA release is also controlled by NE activity which cocaine can increase
Stereotypies
as dose increases, behaviors become focused stereotypies
Acute effects of cocaine
feelings of exhilaration; sympathomimetic physiological effects that include increased heart rate, vasoconstriction, hypertension, insomnia; mania, paranoia and agitation
Mild vs severe effects of cocaine
positive characteristics that contribute to its reinforcing properties become negative with higher dose and duration
Cocaine binges
models of self administration show binges followed by periods of exhaustion
Stimulation of core of NAcc with cocaine
satiating effects of cocaine and conditioned reinforcement
Stimulation of shell of NAcc with cocaine
Cocaine reward
DAT occupancy in humans
once a certain minimum level of DAT occupancy is attained the subject may experience a drug-induced high; cocaine reaches brain faster when smoked or IV; DA release is increased in the striatum, amygdala, hippocampus, and PFC when users are presented with cocaine-related stimuli
DA and craving cocaine
as striatal DA release increases craving results after exposure to cocaine-related stimuli
Cocaine tolerance
decrease in locomotor activity
cocaine sensitization
ncrease in stereotypy after chronic administration
How DA markers change in chronic cocaine users
after chronic use there is a decrease in DA synthesis, release, DAT binding, and D2/D3 binding
Psychosocial treatment
12 step programs, CBT, contingency management
SSRIs for cocaine
increased days sober
Disulfiram for cocaine treatment
inhibits DBH (altering DA-NE ratio)
Cathinone and ephedrine
naturally occurring stimulant compounds
L-amphetamine, D-amphetamine
synthetic, structurally related to DA
Methamphetamine
synthesized from pseudoephedrine, mostly CNS effects
Methylphenidate
treats ADHD
Pipradrol
milder CNS effects, obesity, narcolepsy, ADHD
Bath salts
synthetic cathinone
Administration of amphetamines
ingested orally, IV, or SC
Absorption of amphetamines
a weak base that ionizes in the digestive tract; crosses BBB quickly, concentrates in spleen, kidneys, and brain
Excretion
rate of accretion depends on urine pH; if acidic, it is excreted readily in urine; if basic, it reabsorbs and must be metabolized by liver
Action of amphetamines
indirect catecholamine agonists; stimulate DA and NE release and block reuptake, also affects 5-HT and E
Mechanisms of amphetamines
enter nerve terminal by DAT then stimulates DA release from vesicles and alters DAT to act in reverse direction to release DA into synapse
Amphetamine PNS effects
sympathetic arousal (fight or flight)
Amphetamine CNS effects (3)
1) increased motor activity (nigro-striatal) 2) euphoria and addiction (meso-limbo-cortical) 3) inhibits pituitary function
Amphetamine physiological effects
increased heart rate and blood pressure, vasodilation, brochodilation, reduced sleep time, especially REM
Psychosis
continued meth use can transition to a psychotic state that persists long after abstinence; similar to schizophrenia
Neurotoxicity
damage or death of DA system neurons
Ritalin
activates catecholamine transmission by blocking DAT and NET
Modafinil
binds to DAT with low affinity and acts as a weak DA uptake inhibitor; stimulates release of NE and orexin and inhibits GABA release
MDD
dysphoria, negative thinking, lack of energy, negative life impact
BPD
alternating pattern of depression and mania (or hypomania); mood does not reflect reality
Prevalence of affective disorders
15-20% experience MDD at any given time; 1% experience BPD
Concordance rates
genetics predispose; 65% concordance for identical twins with MDD. 80% for BPD
HPA axis changes in depression
elevated cortisol levels and abnormal circadian rhythm in cortisol secretion; fail to respond to dexamethasone challenge
Sleep changes
rouble falling asleep, almost no stage 3 and 4 SWS, more night wakings, rapid onset of first REM bout
BDP sleep disturbances
sleep deprivation can trigger an episode of mania
Animal models of affective disorders
can only reflect one or a few behavioral symptoms; few models of mania phase or of cycling episodes, several are based on altered circadian rhythms
Monoamine theory of depression
reduced level of monoamines in the CNS is responsible for depressed mood
Support for monoamine theory of depression
tryptophan depletion challenge leads to depression in individuals with family history or relapse in patients on antidepressant drugs
Problems with monoamine theory of depression
cannot explain delay in effects of pharmacology, no solid evidence of abnormal 5-HT in depressed humans, 1/3 of depressed people do not respond to monoamine treatments
MAOIs
first gen, iproniazid; increases amount of neurotransmitters available for release; cause insomnia, weight gain, hypertension, drug interactions
TCAs
first gen, imipramine; inhibition of reuptake (5-HT and NE); potentially dangerous cardiovascular effects and anticholinergic effects
SSRIs
second gen, sertraline, prozac; sexual disfunction, dependence, restlessness, dependence
SNRIs
reboxetine
Ketamine
third gen, enhances BDNF-stimulated neurogenesis and elaboration of dendritic spine growth
ECT
produces up regulation of monoamines and GABA; memory dysfunction and confusion
TMS
similar efficacy for most but not all patients, very new
DBS
anterior cingulate gyrus
Lithium carbonate
eliminates or reduces manic episodes without causing depression, reduces suicide; up regulates 5-HT and down regulates catecholamines
valproate
teratogenic, increases GABA levels; for BPD
carbamazepine - for BPD - inhibits NE reuptake
Light/dark therapy
important in MDD with early morning light, early morning light causes polarity change in BPD patients
