PSY 134 - psychomotor stimulants

sympathomimetics

mimic effects of sympathetic NS (esp NE and DA pathways)

indirect sympathomimetics

structure (beta-phenethylamine); examples (AMPH, meth, cocaine); effect (behavioral activation + arousal, alertness, motor activity)

Alain Baxter

lost bronze medal from 2002 olympics bc of L-meth in urine (IOC doesn’t discriminate b/w L- and D-meth)

COC and monoamine release/reuptake

COC does not cause release of DA/NE/5-HT; COC is most potent at SERT (causes 5-HT reuptake)

AMPH and derivatives on catecholamines

resemble DA/NE, influence their transporters

COC as an indirect sympathomimetic

reuptake inhibition: blocks DAT, so DA remains extracellular and initiates postsynaptic effects

AMPH as an indirect sympathomimetic

releaser: taken up by DAT, inhibits VMAT, prevents vesicular packaging of DA, increases intracellular DA, DA leaks out of DAT, increased extracellular DA, initiates postsynaptic effects

simulants on cognitive performance

stims inc DA levels; cognitive performance is best at a mid-range DA level; if DA is depleted, stim helps improve performace; if not, stim overloads DA and dec performance

stim and hyperactivity

decreases rate of high frequency behaviors + vice versa (therapeutic), narrows behavioral repertoire (therapeutic), BUT increase meaningless behaviors (punding = dismantle/reassembling objects, stereotypy) at high doses

Pharmacokinetics of COC

ionized in digestive system, poor GI absorption; crack (COC salt mixed w baking soda) absorbed better; rapidly metabolized in blood and liver (half life about 1 hour); inactive metabolites present and detectable for up to 3 days

Pharmacokinetics of AMPH

ionized in GI tract, poor absorption; metabolized in liver (half life 12 hours)P

Pharmacokinetics of METH

similar to AMPH; half life 11 hours (smoked) or 12 hours (IV); subjective fx last less than 1 hour (acute tolerance develops rapidly)

alc + addy

unaware of intoxication level, leads to poorer decision making; may cause arrhythmias, paranoia/psychosis, emesis, vertigo, convulsions, headaches (all risks increase when mixed)

alc + COC

cocaethylene, increases risk of cardiovascular toxicity (much higher than any other drug)

stims + antidepressants

synergistic effects (jitteriness, nervousness, anxiety, restlessness, racing thoughts), 5-HT syndrome (overloading of 5-HT), may result in coma or death

stims and animal models

stims used in animal to model psychosis bc they cause psychosis in humans

psychopharmacological adaptations of repeated stim use

euphoria/dysphoria binge cycle (acute eu tolerance, higher dose, dysphoric WD, etc), paranoia (dose dependent, stereotypy); psychosis (inc sens at high doses)

stim WD

few overt physical sxs (very psychological); stage 1 (crash; 9 hr - 4 days): dysphoria-anhedonia, insomnia, irritability; stage 2 (WD; 1-10 wk): anhedonia, dec energy, limited interest in env; phase 3 (extinction; indefinite): craving, both episodic and cue-induced

rats and ICSS on COC WD

inc ICSS threshold (exp dependent); long > short access, inc w inc time during single session

tol and sens to stim

depends on route and frequency of admin; as animals receive more injections/higher doses, they transition from hyperlocomotion to stereotypy, thus sensitization (e.g. 18-MC on COC-induced locomotion: inc until 40 mg/kg)

Delirium during stim WD

hallucinations, confusion, suspicion, persecutory delusions, anxiety

therapeutic interventions for COC addiction

cog-beh/psychodynamic therapy loses effectiveness with inc addiction severity; individual w group counseling is most effective across severities

Pharmacotherapies for COC addiction

D2 partial agonist (e.g. aripiprazole); higher doses showed less of a difference between a COC lever and dummy lever

NAC to target Glu for tx of stim addiction

N-acetylcysteine is a cysteine prodrug, becomes cysteine, system xc- exchanges extracellular cysteine for intracellular Glu, Glu activates mGluR2/3 (inhibitory receptors), decreases Glu release