Week 5 Psychopharmacology

Amino Acid Messengers: Glutamate

Major excitatory neurotransmitter in the CNS • Some people are sensitive to the excitatory effects of glutamate in Monosodium glutamate (MSG) ▫ Can lead to headache, nausea and rapid heartbeat ▫ Although does not cross BBB - synthasised from a-ketoglutarate, in the mitochondria - can be either iontropic or metabotropic Subtypes of glutamate receptors: NMDA, AMPA, and kainate • NMDA unusual as both voltage- and ligand-dependent used to build other proteins - extended action can be toxic

-Neurochemical production

Manipulating the synthesis => affect the amount available for release e.g. more building blocks e.g. carbohydrates=> more tryptophan=> more serotonin.

Administration of drugs

Method of administration leads to different effects on nervous system; blood-brain barrier eating inhalinging and injecting effect all differently .

Identifying Neurochemicals

Substances released by one cell that produce a reaction in a target cell • The substance: ▫ Must be present within a presynaptic cell. ▫ Is released in response to presynaptic depolarization ▫ Interacts with specific receptors on a postsynaptic cell

glycine

an amino acid neurochemical having inhibitory effects in the spinal cord and excititory effects in conjunction with the NMDA glutamate receptor inhibitory in spinal cord excitatory in conjunction with glutimate.

Acetylcholinesterase

an enzyme that breaks down acetylcholine

NMDA

are unique in that they are both voltage-dependant and ligand dependent. they will not open unless glutamate is presant and the post synaptic membrane is depolarized at the same time.

Epinephrine

-Adrenergic neurons -medulla- contain cells that release epinephrine that participate in▫ Regulation of eating, blood pressure adreniline rush is associated with stress is release of epinephrine from the adrenal glands located above the kidneys in th lower back into the blood supply.

neuropeptide

A peptide that acts as a neurotransmitter or neuromodulator or neurohormone. made in cell body requires transport. does not recyle vesicles activation is a high potentila of frequency deactivation diffusion away from the synapse or enzymatic degradation. are metabotropic

Basic Principles of Drug Effects

Administration of drugs • Individual differences • Placebo effects

Small molecules

one of a group of neurochemicals that include amino acids and amine. made in the axon terminal , has recyling vesicles Activation has a moderate action potential frequemcy deactivation reuptake or enzymatic degradation

• Antagonists

reduce the activity of a neurotransmitter • Outcome of action depends on normal synapse e.g. If a neurochemical generally has an inhibitory effect on a postsynaptic neuron, ▫ the agonist would increase the inhibitory effect, ▫ the antagonist would result in less inhibition eg caffine produces alertness . Caffine is an antaginist for adensine which means it reduces adensosines effect because adenosine typically acts as an inhibitor at the synapse ,reduced inhibition due to caffeine equates to increased neural activity. drugs can exert antagonistic effects by interfering with the synthesis pathways of neurochemicals.

Mimic

the action of a neurotransmitter at the site (like a key can open a lock)

influence

the activity of the receptor

Mechanisms of Drug Actions at the Synapse

-Neurochemical production -Neurochemical storage -Neurochemical release

Noradrenergic Systems in the Brain : Norepinephrine

-Noradrenergic neurons ▫ Increases arousal and vigilance ▫ Primary neurotransmitter in the sympathetic nervous system

Mechanisms of Drug Actions at the Synapse: Receptor Effects

-mimic -block -influence

Neurohormone

A chemical messenger that communicates with target cells at great distance often be travelling through the circulation. they travek in the blood supply to reach their final targets.Regardless of the distance traveled these chemical messangers will interact only with other cells that have specialised receptor sites to recieve them.

neuromodulator

A chemical messenger that communicates with target cells more distant than the synapse by diffusing away from the point of release. called volume transmission because large portions of the cns can be influenced remain in the cerebralspinal fluid for extended period of time .

mesostriatal (nigrostriatal) pathway

A dopaminergic pathway originating in the substantia nigra and projecting to the basal ganglia

mesolimbocortical system

A dopaminergic pathway originating in the ventral tegmentum of the midbrain and projecting to the limbic system and cortex

gasotransmitter

A gas such as nitric oxide that performs a signalling function.

LSD

A hallucinogenic drug that resembles serotonin. appears to actas a seotronergic agonist in cerebral cortex

norepinephrine

A major monamine and catecholamine neurotransmiter. - neurons that secrete norepinephrine are found in the pons medulla and hypothalamus. - most significant source is from the locus coeruleus of the pons. -Released norepinephrine goes to nearly every major part of the brain and spinal cord, producing arousal and vigilance. - b receptors metabotropic.

Dopamine

A major monoamine and catecholamine neurotransmittwr implicated in motor control. reward and psychosis. Dopamine systems are involved with motivated behaviours and processing of reward. addiction to drugs ( and some behaviours like gambling) is especially influenced by activity in circiuts using dopamine.

Neurochemical release

Can be modified in response to the arrival of an action potential by drugs

Small-Molecule Neurochemicals: Monoamines

Catecholamines • Indoleamines

Placebo effects

User expectations influence drug effects ▫ Double-blind experiment

Dopaminergic Systems in the Brain

Dopaminergic neurons in the midbrain form connections with other neurons • Dopamine activity is associated with motivated behavior and reward processing two patheways: mesostriatal (nigrostriatal) pathway and mesolimbocortical pathway

• Individual differences

Drug effects influenced by body weight, gender, and genetics

parts of the brain associated with the dopaminergic pathway

Frontal lobe, basal ganglia, nucleus accumbens, amgdala, hippocampus, ventral tegmental area substantia nigra , limbic system, hypothalamus, thalamus olfactory cortex

• Tolerance

Lessened effects as a result of repeated administration. the process in which more of a drug is needed to produce the same efffect.

Neurotransmitters

Participate in directed synapses by acting on neurons in their own immediate vicinity

Types of Neurochemicals

Small-Molecules Neuropeptides gasotransmitters

reuptake inhibitor

Substance that interferes with the transport of released neuro transmitter molecules back into the pre synaptic terminal.

Indoleamines: Serotonin

Synthesized from tryptophan (dairy, grains) • Regulates mood, sleep, and appetite • Motivation to consume carbohydrates • Antidepressant medication increases activity of serotonin. • Low levels related to low social rank, increase risk taking and aggression. - most serotonergic neurons are found in the raphe nuclei of the brainstem. serotonin released by these neurons effect the spinal cords, cerebellum,limbic system and cerebral cortex.

area postrema

a brainstem area in which th blood barrier is more permeable that triggers vomiting in response to the detection of circulating toxins

nicotinic reseptor

a posy synaptic receptor that responds to acetylcholine and nicotine.

muscarinic receptor

a posy synaptic receptor that responds to both acetylcholine and muscarine.

Agonists

enhance the activity of a neurotransmitter promote increased production Outcome of action depends on normal synapse e.g. If a neurochemical generally has an inhibitory effect on a postsynaptic neuron, ▫ the agonist would increase the inhibitory effect, ▫ the antagonist would result in less inhibition

Amino acid

essential component of protein.

Small molecules spilt into two groups

monoamines Amino acids

block

the synaptic activity by occupying a binding site (like similar but wrong key)

Marijuana (Cannabis)

• Active ingredient THC is an endogenous cannabinoid receptor agonist • Cannabinoid receptors are in the hippocampus and prefrontal cortex • Effects: mild euphoria, perceptual distortion, hallucination, and depression

The Distribution of Cholinergic Systems in the Brain

• Distributed in PNS and brain • Participate in attention, wakefulness and memory. • Two cholinergic receptor types: ▫ Nicotinic receptors (ionotropic) ▫ Muscarinic receptors (metabotropic)

Alcohol

• GABAa receptor agonist • Stimulates dopaminergic reward pathways • Rapid tolerance • Damaging effects on health - stimulates dopamininergic pathways and antagonizes the NMDA glutamate receptor.

Effects of Psychoactive Drugs: Stimulants

• Increase alertness and mobility ▫ Caffeine - adenosine antagonist- inhibition in the hippocampus and cerebral cortex. ▫ Nicotine - nicotinic cholinergic receptor agonist ▫ Cocaine - dopamine reuptake inhibitor ▫ Amphetamine - stimulates release and inhibits reuptake of dopamine/norepinephrine ▫ Ecstasy (MDMA) - stimulates release of serotonin and oxytocin; toxic to serotonergic neurons. seretonin is pumped into the gap where it is now trapped

Opioids

• Interact with endorphin receptors ▫ Pain relief, relaxation, sense of euphoria • Opiates ▫ Derived from opium poppy ▫ Morphine, codeine ▫ Heroin Synthetic opiate Derived from morphine

Amino Acid Messengers: GABA

• Major inhibitory neurochemical in the CNS • Synthesized from glutamate • GABAA and GABAB receptors ▫ GABAa receptors interact with psychoactive drugs, (ionotropic) chloride channels which allow negativley charged chloride ions to enter the cell. GABAb receptors (metabotropic) potassium channels. allow positivly charged potassium ions to leave the cell

Small-Molecule Neurochemicals: Acetylcholine

• Produced in cholinergic neurons and also as a result of activity of mitochondria • Primary NT at neuromuscular junction • Also important in autonomic nervous system

Reuptake effects

▫ Cocaine, amphetamine, and Ritalin inhibit dopamine reuptake ▫ SSRIs (e.g., Prozac) inhibit serotonin reuptake • Deactivation of neurotransmitters

Addiction

▫ Compulsive need to use the drug repeatedly despite harm to the user

catecholamines

▫ Dopamine, norepinephrine, epinephrine ▫ Synthesized from tyrosine

Neurochemical storage

▫ Interfering with the storage in vesicles

Withdrawal

▫ Occurs when substance use is discontinued; opposite of the effects caused by the discontinued drug

Enzymatic degradation

▫ Organophosphates interfere with Acetylcholinesterase (AChE) • Deactivation of neurotransmitters

Indoleamines

▫ Serotonin, melatonin ▫ Serotonin is synthesized from tryptophan