NEUROTRANSMITTER

Neuroscience of Clinical Psychiatry, The: The Pathophysiology of Behavior and Mental Illness, 1st Edition

• A neurotransmitter is technically defined by meeting three criteria:
1. The substance must be stored in the presynaptic neuron. 2. It must be released with depolarization of the presynaptic neuron induced by the influx of Ca2+. 3. The substance must bind with a specific receptor on the postsynaptic neuron

Neuroscience of Clinical Psychiatry, The: The Pathophysiology of Behavior and Mental Illness, 1st Edition

Amino acids: 1. Acetylcholine 2. 2. 1st Edition . Neuropeptides. 3.CLASSIFICATION OF NEUROTRANSMITTER 1. Gases : Nitric oxide (NO) Endocannabinoids Neuroscience of Clinical Psychiatry. The classic neurotransmitters: 1. Unconventional neurotransmitters 1. 3. Monoamines 1. 2. Glutamate GABA and Glycine Catecholamines 1. The: The Pathophysiology of Behavior and Mental Illness. 3. 2. Indoleamines 1. 2. 2. 3. Dopamine Norepineprhine Epinephrine Serotonin Melatonin Histamine 2.

Neuropeptides Neuropeptides Gut-brain peptides Example Pituitary peptides Hypothalamic releasing peptides Opioid peptides Other peptides Substance P Cholecystokinin Galanin Adrenocorticotropic hormone (ACTH) Luteinizing hormone (LH) Oxytocin Vasopressin Corticotropin-releasing factor (CRF) Gonadotropin-releasing hormone (GnRH) Thyroidtropin-releasing hormone (TRH) Somatostatin Endorphin Enkephalins Angiotensin Bradykinin Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

Unconventional neurotransmitters 1. Endocannabinoids Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. Gases 2. 1st Edition .

Neuroscience of Clinical Psychiatry. 1st Edition . The: The Pathophysiology of Behavior and Mental Illness.

Note that L-dopa is synthesized into DA. The: The Pathophysiology of Behavior and Mental Illness.Catecholamines are synthesized from the essential amino acid tyrosine that must be obtained from the diet. The trick is to allow the synthesis in the CNS. Neuroscience of Clinical Psychiatry. but inhibit the enzyme dopa decarboxylase in the periphery so that the patient is not too nauseated. The synthesis of catecholamines from tyrosine. This shows why L-dopa can be given as a treatment for Parkinson's disease. 1st Edition .

The relative size of -A : the amino acids -B : two of the amines -C : neuropeptide Neuroscience of Clinical Psychiatry. 1st Edition . The: The Pathophysiology of Behavior and Mental Illness.

glutamate must be synthesized in the brain from glucose and other precursors. Consequently. 1st Edition . • Glutamate and another excitatory transmitter aspartate are nonessential amino acids that do not cross the blood-brain barrier. • Glial cells assist in the reuptake.Glutamate • This is the major workhorse of the brain. The: The Pathophysiology of Behavior and Mental Illness. • Disorders: – Too much glutamate (as in stroke) is toxic to the nerve cells – glutamatergic dysregulation may be present in patients with schizophrenia Neuroscience of Clinical Psychiatry. degradation. and resupply of glutamate for neurons. with glutamate neurons making up more than half of the excitatory neurons. Without glutamate the brain does not get started or keep running.

The: The Pathophysiology of Behavior and Mental Illness.Neuroscience of Clinical Psychiatry. 1st Edition .

• GABA puts the brakes on the brain: not enough GABA and one can have seizures. The: The Pathophysiology of Behavior and Mental Illness. Neuroscience of Clinical Psychiatry.GABA and Glycine • GABA is the major inhibitory transmitter in the brain and is used by approximately 25% of the cortical neurons. 1st Edition . but is less common. • The GABA neurons are primarily the interneurons in the gray matter providing local constraint over cortical circuitry. • Glycine is the other inhibitory amino acid.

amygdala. 1st Edition . and hippocampus.Dopamine (DA) There are 3 dopaminergic system in the brain: 1. antipsychotic medications that block the DA receptor can cause an increase in prolactin (hyperprolactinemia) Neuroscience of Clinical Psychiatry. Mesolimbic : from ventral tegmental area (VTA) to nucleus accumbens. The: The Pathophysiology of Behavior and Mental Illness. Tuberoinfundibular DA system : – – From Arcuate nucleus to hypophysis inhibit synthesis and release of prolactin. Mesocortical : from VTA to prefrontal cortex 3. Mesolimbocortical DA system: 1. 2. Nigrostriatal system or Mesostriatal system : – From Substantia nigra to striatum (nucleus Caudatus and Putamen)Parkinson disease 2.

The: The Pathophysiology of Behavior and Mental Illness. and seem to be impaired in patients with attention deficit hyperactivity disorder (ADHD). • The branches to the prefrontal cortex are involved with attention and cognition. • Some speculate that problems with the mesolimbic system cause the positive symptoms of schizophrenia whereas negative symptoms are caused by impairment in the mesocortical system. 1st Edition . Neuroscience of Clinical Psychiatry.Dopamine (cont.) • The branches to the nucleus accumbens are involved with reward and substance abuse.

The: The Pathophysiology of Behavior and Mental Illness.The dopaminergic system The substantia nigra forms the nigrostriatal pathways to the caudate and putamen. The arcuate nucleus of the hypothalamus projects to the tuberoinfundibular area of the hypothalamus Neuroscience of Clinical Psychiatry. The ventral tegmental area projects to the nucleus accumbens and cortex. 1st Edition .

Norepinephrine (NE) • NE neurons contain an additional enzyme in their terminals that converts DA to NE. • Approximately 50% of the NE neurons are located in the locus coeruleus.000 neurons in each nucleus. There are approximately 12. Neuroscience of Clinical Psychiatry. • Plays an important role in anxiety and depression. • The remainder of the NE neurons is found in loose clusters in the medullary reticular formation . The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

) • The NE neurons play an important role in alertness. • The firing of the locus coeruleus increases along a spectrum from drowsy to alert. the locus coeruleus is active as are the sympathetic neurons of the autonomic nervous system (ANS) where the peripheral noradrenergic neurons are found. In a threatening situation. The: The Pathophysiology of Behavior and Mental Illness. • The noradrenergic neurons are important in handling danger.Norepinephrine (cont. with the lowest found when we sleep and the highest when we are hypervigilant. Neuroscience of Clinical Psychiatry. 1st Edition .

Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. the NE system plays an important role in alertness and anxiety. 1st Edition .The noradrenergic system. With projections to almost every area of the brain and spinal cord.

1st Edition . epinephrine plays a much greater role outside of the brain as a hormone. The: The Pathophysiology of Behavior and Mental Illness. • Therefore.Epinephrine • The epinephrine (or adrenaline) neurons are few and play a minor role in the CNS. than within as a neurotransmitter Neuroscience of Clinical Psychiatry. • Most of the epinephrine in the body is produced in the adrenal medulla and excreted with sympathetic stimulation.

Serotonin synthesis Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

Serotonin (5-hydroxytryptamine) • Serotonin is found in many parts of the body outside of the CNS. • The most closely associated neurotransmitter with modern neuropsychopharmacology. • As with NE. such as platelets and mast cells.000) and reside in the raphe nuclei in the brain stem. the serotonin neurons project to virtually all areas of the brain. Only approximately 1% to 2% of the body's serotonin in located in the brain. • The serotonin neurons are relatively few in number (approximately 200. • Serotonin is synthesized from tryptophan that must be obtained in the diet . • Plays an important role in depression and anxiety. • In the pineal gland there are two additional enzymes that convert serotonin to melatonin. Neuroscience of Clinical Psychiatry. and also in the sleep-wake cycle. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

1st Edition . and with the sleep-wake cycle Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. anxiety. These neurons play an important roll in mood.The serotonergic system The cluster of Raphe nuclei along the brainstem has projections to most of the brain and spinal cord.

• Most of the cell bodies start in the tuberomammilary nucleus of the posterior hypothalamus. • When animals are alert. there has been increased interest in activating the histamine neurons as a treatment for fatigue. the only agent in the class. Modafinil. indirectly activates the histamine neurons and has been used successfully as a treatment for narcolepsy. with sparse but widespread projects to all regions of the brain and spinal cord. Neuroscience of Clinical Psychiatry. Histamine neurons are quiet when animals are sleeping. • More recently. and ADHD. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition . excessive sleepiness.Histamine • Histamine in the brain is involved in arousal and attention. the histamine neurons are active.

Disruption of this balance with DA-blocking antipsychotic agents can result in extrapyramidal side effects. 1st Edition . unlike the catecholamines and indoleamines. The anticholinergic agents are administered to restore the ACh/DA balance and allow normal movement. • ACh plays a prominent role : – in the peripheral autonomic nervous system (ANS) – at the neuromuscular junction. • In the CNS arises from cell bodies in the brain stem and forebrain with prominent projects to the cortex and hippocampus. • ACh.Acetylcholine • Acetylcholine (ACh) was the first neurotransmitter identified (1920) • ACh is a small molecule transmitter but it is not an amino acid nor a monoamine. The: The Pathophysiology of Behavior and Mental Illness. • In the striatum. • Projections to the hippocampus are involved with learning and memory and are disrupted in Alzheimer's disease. Neuroscience of Clinical Psychiatry. is also synthesized in interneurons in the CNS. the ACh neurons balance the dopaminergic input from the substantia nigra to coordinate extrapyramidal motor control.

• Some have important endocrine functions in the body. neuropeptides are not recycled by the neuron. • The formation. and inactivation of the neuropeptides differ from that of the monoamines. such as the regulation of reproduction. temperature control.Neuropeptides • The neuropeptides are small chains of amino acids but larger than the classic neurotransmitters. Initially the peptide is a large propeptide precursor. salt metabolism. water intake. Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. release. • Unlike the monoamines. growth. Peptides are synthesized in nerve cells and have effects on behaviors such as learning. mood. and anxiety. Peptides must be transcribed from mRNA on the ribosomes of the endoplasmic reticulum. but are rather broken down by degradative enzymes (peptidases) on the receptor membrane. 1st Edition . attachment. which is cleaved into an active neuropeptide as it is moved from the Golgi apparatus into large dense core vesicles that are stored at the terminal bud of the neuron.

Neuropeptides Neuropeptides Gut-brain peptides Example Pituitary peptides Hypothalamic releasing peptides Opioid peptides Other peptides Substance P Cholecystokinin Galanin Adrenocorticotropic hormone (ACTH) Luteinizing hormone (LH) Oxytocin Vasopressin Corticotropin-releasing factor (CRF) Gonadotropin-releasing hormone (GnRH) Thyroidtropin-releasing hormone (TRH) Somatostatin Endorphin Enkephalins Angiotensin Bradykinin Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

Neuroscience of Clinical Psychiatry. The: The Pathophysiology of Behavior and Mental Illness. 1st Edition .

– NO has the ability to diffuse (without obstruction) out of the originating cell. – is a gas that is formed in glutamate neurons when arginine is converted into citrulline and NO.Unconventional Neurotransmitters • Nitric oxide (NO) : – most commonly associated with erectile dysfunction. 1st Edition . but reach out so extensively that nearly every cell in the brain may encounter NO. NO may restrain aggressive and sexual behavior. Neuroscience of Clinical Psychiatry. – It is worth noting that the medications for erectile dysfunction have not been associated with any adverse effects on mental function. The: The Pathophysiology of Behavior and Mental Illness. through the extracellular medium and into any neighboring cell that it meets. – NO converts guanosine triphosphate (GTP) into cyclic guanosine monophosphate (GMP) that acts as a second messenger. – NO may be involved with aggression and sexual behavior. – Cells containing the NO synthase (the enzyme that creates NO) constitute only approximately 1% of neuronal cells in the brain. This may be due to the inability of these medications in their current form to cross the blood-brain barrier. as well as migraine headaches.

) • Endocannabinoids: – The cannabinoid receptor (CB1) is widely expressed throughout the brain on presynaptic terminals. has been shown in clinical studies to facilitate weight loss. – The effect of activating CB1 receptors results in inhibition of that neuron and in a simple way explains the calming effect of marijuana. – Blocking the CB1 receptor can inhibit appetite.Unconventional Neurotransmitters (cont. The: The Pathophysiology of Behavior and Mental Illness. Neuroscience of Clinical Psychiatry. a potent and selective blocker (antagonist) of the CB1 receptor. 1st Edition . – Rimonabant.