exam 2 - neurotransmission and drugs

agonist

a drug or substance that turns on a neurotransmitter system through EPSPs or IPSPs

antagonist

a drug or substance that acts on a synapse to suppress or reverse normal synaptic activity (turns off a neurotransmitter system)

inverse agonist

a drug or substance that acts postsynaptically by binding to a receptor, inducing an opposite or different effect

presynaptic agonists include

• L-DOPA

• cocaine

• amphetamine

• selective serotonin reuptake inhibitors (SSRIs)

L-DOPA

• presynaptic agonist (activates a neurotransmitter system)

• l-dopa is a precursor to dopamine (cells can make dopamine out of it)

• increased levels of dopamine, may aid in movement for conditions like parkinson’s

  • dopamine itself cannot be prescribed because it is too large to pass through the blood-brain barrier

cocaine

• presynaptic agonist (activates a neurotransmitter system)

• inhibits the reuptake of dopamine by blocking a dopamine transporter; keeps dopamine in the synapse, increases binding to receptors and duration of binding

amphetamine

• presynaptic agonist (activates a neurotransmitter system)

• blocks and reverses dopamine transporter, acts on dopaminergic synapses; can also act on norepinephrine

• increases levels of dopamine, norepinephrine

• stimulation, wakefulness, improved cognitive control - treatment of ADHD, narcolepsy

• adderall = combo of amphetamine and dextroamphetamine

selective serotonin reuptake inhibitors (SSRIs)

• presynaptic agonist (activates neurotransmitter system)

• acts on serotonergic synapses and blocks reuptake of serotonin; magnifies effects of serotonin

• commonly prescribed antidepressant: prozac

postsynaptic agonists include

• morphine, heroin, and synthetic opiods

• benzodiazephines

morphine, heroin

• postsynaptic agonists (activate a neurotransmitter system)

• activate opioid receptors

• mimic endorphins and enkephalins (natural opioids)

• effects are more intense (euphoria, pain relief)

synthetic opioids: fentanil and carfentanil

• postsynaptic agonists (activate a neurotransmitter system)

• human-made in laboratory

• fentanil is 100x more potent than morphine; carfentanil is 100x more potent than fentanil - makes overdose much more likely; harmful/lethal because it interrupts breathing circuits

benzodiazephines

• postsynaptic agonists (activate neurotransmitter system)

• bind to gaba receptors and facilitate gaba effects: inhibit and reduce activity and post-synaptic spikes by allowing higher influx of anions

  • still needs gaba to bind but amplifies effects

• sedative, anti-anxiety, hypnotic, muscle relaxant

• ex. xanax, valium

postsynaptic antagonists include

• antipsychotic drugs for schizophrenia: block D2 dopamine receptors and prevent dopamine from acting

• atypical antipsychotics: block both dopamine and serotonin receptors

• turn off neurotransmitter systems

routes of drug administration

• oral ingestion: drug is taken orally, digested, absorbed to blood, circulated, and enters the brain

• injection: includes subcutaneous (just under skin), intramuscular (goes into muscle), and intravenous (straight into blood, shortest path and maintains concentration of drug)

• inhalation: short path from lungs to brain - quick effect, increased concentration

long-term effects of chronic/continued usage of drugs

1. receptor down-regulation

2. neural sensitization

3. neurotoxicity

receptor down-regulation

• tolerance to drug

• overactivation of receptors is detected by the postsynaptic cell → homeostatic regulation (receptor degradation) to compensate for overactivation → same amounts of drug will have lowered effects

• may be reversible if drug is not taken allowing receptors to reappear

neural sensitization

• hyper-responsive to drug

• “repeated intermittent exposure to a given stimulus results in an enhanced response at subsequent exposures” (from an nih article)

• ex. dopamine sensitization and addiction; can act on pleasure and motivation circuits differently

neurotoxicity

• very rare

• amphetamine can kill dopamine neurons at high dosages

• neurons dying and being killed :(