PSB3004C Physiological Psychology Quiz 3 Ch 4 Summary 1 The major transmitter families include acetylcholine the monoamines the amino acid transmitters and the peptides Additional transmitters that do not fit the usual criteria include gaseous transmitters especially nitric oxide NO and other retrograde transmitters like anandamide which binds to cannabinoid receptors 2 Acetylcholine was the first identified transmitter Remember Otto Loewi s dream It is the transmitter at neuromuscular junctions in parasympathetic neurons including the vagus which slows the heart and in several basal forebrain nuclei that project to the hippocampus and widely throughout the brain to arousal and memory One factor in Alzheimer s disease is loss of cholinergic innervation of the brain 3 There are 2 cholinergic receptor subtypes nicotinic and muscarinic Nicotinic receptors are on muscles and in the brain They are ionotropic and excitatory Muscarinic receptors are metabotropic they mediate parasympathetic effects and are also in the brain Different subtypes of muscarinic receptors can be excitatory or inhibitory Curare blocks nicotinic receptors and paralysis botulinum toxin Botox blocks ACh release and paralysis 4 Monoamine transmitters include the catecholamines dopamine norepinephrine and epinephrine and the indoleamines serotonin and melatonin 5 There are 2 major dopaminergic nuclei in the midbrain substantia nigra and the ventral tegmental area VTA The nigrostriatal tract is critical for motor control Degeneration Parkinsonson s disease overactivity obsessive compulsive disorder The mesocorticolimbic a k a mesolimbic tract is the engine driving motivated behavior Drugs of abuse increase dopamine release in this tract either directly or indirectly 6 Norepinephrine is the postganglionic transmitter for the sympathetic nervous system it is also in neurons that branch widely throughout the brain and that arousal The locus coeruleus blue place is a major nucleus that sends NE throughout the brain 7 Epinephrine is primarily a hormone from the adrenal medulla but there are a few neurons in the brain that use epinephrine 8 Serotonin 5 hydroxytryptamine 5 HT is produced by neurons in the raphe nuclei of the midbrain and brainstem 5 HT neurons fire most during rhythmic activity and may cause sleep disruption SSRI selective serotonin reuptake inhibitor antidepressants keep 5 HT in the synapse longer Rhythmic exercise increases 5 HT and also is antidepressive 9 The primary amino acid transmitters are glutamate which is the major excitatory transmitter in the brain and GABA which is the major inhibitory transmitter in the brain Aspartate is also excitatory but is a transmitter at fewer synapses Glutamate is critical for learning and memory but too much can be excitotoxic and kill neurons as during a stroke There are two major types of glutamate ionotropic receptors AMPA and NMDA A third less common one is kainate Ketamine blocks NMDA receptors and can be used to treat a stroke it can also mimic symptoms of schizophrenia more about this later There are also metabotropic glutamate receptors that have various effects GABAA receptors are ionotropic and open Cl channels to hyperpolarize cells GABAA agonists like Valium are tranquilizers GABAB receptors are metabotropic and also have various effects 1 PSB3004C Physiological Psychology Quiz 3 10 Exogenous opiates such as morphine are powerful analgesics and have considerable potential for abuse Opioid peptides mimic the effects of opiate drugs such as morphine and heroin Several different types of opiate receptors have now been identified along with a number of endogenous opioid peptides enkephalins endorphins and dynorphins 11 Nitric oxide NO is a gaseous transmitter and is often produced in postsynaptic cells from where it diffuses back to the presynaptic cell It acts through cGMP and may promote neurotransmitter release It is also the major vasodilator of the body Viagra prolongs cGMP s actions and erections 12 Endocannabinoids activate the same receptors as marijuana One endogenous ligand is anandamide which is a retrograde transmitter that inhibits release of glutamate and or GABA 13 Drugs may affect many different aspects of presynaptic function such as alteration in transmitter synthesis storage or release as well as alteration in autoreceptor function blockade of reuptake and inhibition of breakdown enzymes 14 Drugs may affect many different aspects of postsynaptic function including activation or blockage of postsynaptic receptors alteration in second messenger activity alteration in gene expression and up and down regulation of postsynaptic receptor density 15 Ligand molecule that binds to a receptor Agonist a molecule that stimulates a receptor or increases transmitter release Antagonist a molecule that blocks a receptor 16 Repeated use of some drugs tolerance or sensitization to the drug s effects Repeated use of agonists may decrease the numbers of postsynaptic receptors making later drug doses or even natural reinforcers less able to elicit a response This is referred to as tolerance and may result in withdrawal symptoms Cross tolerance is the reduced responsiveness to drugs that are similar to the one that was repeatedly used However some drug responses can become stronger rather than weaker a process called sensitization Drug sensitization is thought to underlie drug craving On the other hand repeated use of antagonists may increase the postsynaptic receptors so that neurons can respond to lower amounts of natural stimulation 17 In some cases stimulant drugs act as an agonist mimicking the effects of a neurotransmitter other stimulants act by directly or indirectly altering the concentration of neurotransmitter in the synapse still others act by altering the actions of neuromodulators such as adenosine 18 Cocaine and Ritalin act by blocking reuptake of dopamine the difference in their effects results from the slow onset and offset of Ritalin s effects Amphetamine makes dopamine vesicles leaky resulting in dopamine spilling into the cytoplasm it also reverses the dopamine transporter pumping the dopamine out of the neuron into the synapse 19 Caffeine is an exogenous neuromodulator that blocks the effect of adenosine an endogenous neuromodulator that normally inhibits catecholamine release Adenosine is co released with catecholamines and acts on autoreceptors to inhibit further release of the catecholamines Since caffeine blocks those inhibitory