physiology of drug addiction

What pathway is implicated in addiction?

mesolimbic dopaminergic pathway (dopamine reward pathway)

activation of the reward pathway does what?

increases dopamine

explain the two parts of the mesolimbic dopaminergic pathway

ventral tegmental area: where the dopamine is produced

limbic area (mostly the nucleus accumbens, but also the amygdala and hippocampus)

What target of the mesolimbic dopaminergic pathway is the limbic area and responsible for habit formation and pleasure?

nucleus accumbens

Explain the reward pathway activation by normal things vs drugs

the pathway’s purpose is to help us predict rewards and associate rewards with actions, so once we make that association and prediction then the reward aspect goes away because the pathway stops being activated

with drugs they directly act on the pathway and then you don’t have the inactivation of the pathway like you normally would

What are the three major categories of drugs?

stimulants, depressants, and hallucinogens

What drugs are the stimulants? 4

amphetamines, cocaine, nicotine, and caffeine

What drugs are the depressants? 4

opioids, alcohol, benzodiazepines, and barbiturates

What drugs are the hallucinogens? 4

PCP (phencyclidine), LSD, marijuana, and NDMA (ecstasy)

What drug?

MOA: use dopaine transporter to get into presynaptic terminal; then uses VMAT to enter vesicles, dopamine concentration reaches threhold and that reverses the action of DAT

amphetamines

intoxication: mydriasis, could cause cardiac arrest and seizures, mood elevation, phsychonotos agitation, insomnia, cardiac arrhythmias, tachycardia, and anxiety

amphetamines

MOA: inhibits the reuptake of dopamine by inhibiting DAT

also inhibits the reuptake of other catecholamines

cocaine

what drug’s treatment is an alpha blocker or benzo but not a beta blocker?

why no beta blocker?

cocaine

if beta receptors are blocked then the excess catecholamines will bind to the alpha receptors causing further vasoconstriction

MOA: binds to nicotinic ACh receptors in the ventral tegmental area; depolarization of the bouton increases dopamine release

nicotine

MOA: binds to a mu-opioid receptor in the GABAergic interneurons and inhibits those cells, increases dopamine release

opioids

symptoms: constipation with intoxication then diarrhea with withdrawal and yawning and lacrimation

opioids

MOA: increases the release of beta-endorphins, which bind to the mu-opioid receptors to inhibit GABA which allows for dopamine release

alcohol

intoxication: ataxia, blackouts, coma, disinhibition, emotional lability, slurred speech

severe withdrawal: life threatening tremors 2-4 days after last drink and visual hallucinations

alcohol

MOA: increases the frequency of Cl- channel opening with stops GABA which allows dopamine release

benzodiazepines

benzodiazepines bind to the _____ receptors not the _____ receptors

alpha-1 GABA-A receptors not the Alpha-3 GABA-A receptors

MOA: binds to the GABA-A receptors and increases the duration of Cl- channel opening

barbiturates

intoxication: marked respiratory depression, CNS depression, and CV depression

barbiturates

MOA: NMDA glutamate receptor antagonist with inhibits GABA to increase dopamine

PCP (phencyclidine) (angel dust)

intoxication: violence, nystagmus, and trauma

PCP (phencyclidine)

MOA: serotonin 5HT2 partial agonist

intoxication: sensory misperception

LSD (lysergic acid diethylamide)

MOA: activates CB1 receptor on GABA interneuron to inhibit GABA to let dopamine be released

marijuana

intoxicatio: delayed reaction time, impaired judgement, increased appetite

withdrawal: irritable, decreased appetite, restlessness

can be detected in urine 7-10 days after use is casual users, 1 month in chronic users

marijuana

MOA: works on the dopamine system but mainly on serotonin neurotransmitter; uses SERT to displace serotonin from VMAT which leads to an increase of concentration of serotonin

MDMA (Ecstasy)

Intoxication: hyperthermia, hyponatremia, serotonin syndrome

withdrawal: depression, fatigue, change in appetite, anxiety

MDMA (ecstasy)

Dopamine production, packaging, and subsequent release is accomplished in this brain structure, which is a target of many addictive drugs

ventral tegmental area