Slide 1MonoaminesMonoaminesMonoaminesMonoaminesMAO InhibitorsMonoaminesMonoamines STPAnatomy of Vertebrate BrainTelencephalonDiencephalonMesencephalonMetencephalonMyelencephalonSerotonin as a NeurotransmitterSerotoninSerotoninDopamine as a NeurotransmitterNigrostriatal Dopamine SystemNigrostriatal Dopamine SystemMesolimbic Dopamine SystemMesolimbic Dopamine SystemMesolimbic Dopamine SystemNorepinephrine as a NeurotransmitterNorepinephrine as a NeurotransmitterADDAmino Acids as Excitatory NeurotransmittersAmino Acids as Inhibitory Neurotransmitters- GlycineAmino Acids as Inhibitory Neurotransmitters- GABAPolypeptides as NeurotransmittersPolypeptides as NeurotransmittersEndocannabinoids as NeurotransmittersNitric Oxide as NeurotransmitterNitric Oxide in erection of penisNitric Oxide and ViagraCarbon Monoxide as NeurotransmitterPhysiology Exam 2 (Chapter 7)Monoamines•A variety of chemicals in the CNS function as neurotransmitters. Among these are the monoamines, a chemical family that includes dopamine, norepinephrine, and serotonin. Monoamines are regulatory molecules derived from amino acids.Monoamines•Dopamine, norepinephrine, and epinephrine are derived from the amino acid tyrosine and placed in a subfamily of monoamines called catecholamines. •Dopamine is a neurotransmitter, norepinephrine is a neurotransmitter and a hormone (from the adrenal medulla), and epinephrine is the primary hormone secreted by the adrenal medulla. •Serotonin is derived from the amino acid tryptophan and functions as an important neurotransmitter.Monoamines•Monoamines are produced and stored in synaptic vesicles. Action potentials open gated Ca2+ channels, monoamine neurotransmitters are released by exocytosis from presynaptic vesicles, diffuse across the synaptic cleft, and interact with specific receptor proteins in the membrane of the post synaptic cell.Monoamines•The stimulatory effects of those monoamines must be quickly inhibited to maintain proper neural control. The action of monoamine neurotransmitters at the synapse is stopped by the reuptake of the neurotransmitter molecules from the synaptic cleft into the presynaptic axon terminal, and degradation of the monoamine by an enzyme within the axon terminal called monoamine oxidase (MAO).MAO Inhibitors•Monoamine oxidase (MAO) inhibitors are drugs that block MAO (the enzyme primarily responsible for degrading the monoamine neurotransmitters). By preventing the breakdown of monoamines, these drugs increase the amount of neurotransmitters in the synaptic cleft. •MAO inhibitors have proven useful in treatment of depression suggesting that a deficiency in monoamine neurotransmission contributes to this disorder.• An MAO inhibitor drug called catecholomethyltransferase (COMT) is used to treat Parkinson’s disorder because it increases the amount of dopamine at the synapse. COMT inactivates catecholamines by putting methyl group on catecholamines.Monoamines•Monoamines cross plasma membrane through the signal transduction pathway. Monoamine neurotransmitters act with the help of a second messenger to open ion channels in post synaptic membrane.Monoamines STP•In some synapses that use catecholamines for synaptic transmission, this second messenger is cyclic adenosine monophosphate (cAMP).• For example, binding of norepinephrine with its receptor in the post synaptic membrane stimulates the dissociation of the G protein alpha subunit from the others in its complex. This subunit diffuses in the membrane until it binds to an enzyme known as adenylate cyclase. This enzyme converts ATP to cyclic AMP (cAMP) and pyrophosphate (2 inorganic phosphates) within the post synaptic cell cytoplasm. Cyclic AMP in turn activates enzyme protein kinase which phosphorylates (add phosphate group) other proteins. Through this action, ion channels are opened in the post synaptic membrane.•Pathway turns off by enzyme Phosphodiesterase (PDE) by it breaking down cAMP. Protein Phosphate takes off phosphate, reverse activity of protein kinase.Anatomy of Vertebrate Brain•Forebrain divides into Telencephalon and Diencephalon. Midbrain is Mesencephalon. Hindbrain divides into the Metencephalon and Myelencephalon.Telencephalon•Telencephalon is the cerebral hemispheres which form the cerebrum. Cerebrum has four lobes and is involved in the limbic system and basal nuceli. The four lobes are responsible for conscious thought process and intellectual functions. Limbic system involves the amygdala (emotion processing) and hippocampus (memory storage and processing). Basal nuclei is involved in movement regulation and skill learning.Diencephalon•The Diencephalon is much smaller and shaped like a box. The roof of the box is the epithalamus (pineal gland), the side walls of the box is the thalamus (relay and processing center for sensory information), and the floor of the box is the hypothalamus (controls emotions, autonomic functions/interacts with ANS, and hormone production). The ganglion from floor of hypothalamus is the pituitary gland.Mesencephalon •Mesencephalon is the midbrain, processes visual and auditory data and control of reflexive responses, and maintenance of consciousness. Mesencephalon is enlarged and most important in fish. Two important regions are the tectrum (roof) and the tegmentum (floor). Neurons producing dopamine have cell bodies in tegmentum of mesencephalon.Metencephalon •Metencephalon has two major components: the pons (part of the brainstem) and cerebellum. Cerebellum is important in the unconscious control of skeletal muscles like learning how to ride a bike. If you stimulate the cerebellum, it can’t make the muscles contract. Animals that have the most complex movements, like birds and fish, have large cerebellums.Myelencephalon •Myelencephalon is the brainstem. The medulla oblongata in the brain stem relays information between the spinal cord and the brain and is involved in controlling the ANS, heart rate, and respiratory rate. The pons is between midbrain and medulla oblongata and a fiber tract that relays information back and forth from the cerebellum. Pons also contains Raphe nucleus (where Serotonin is synthesized).Serotonin as a Neurotransmitter•Serotonin is used as a neurotransmitter by neurons with cell bodies in the raphe nuclei that are located in the midline of the brainstem. LSD exert their effects primarily by binding to and activating serotonin receptors in the cerebral cortex. Serotonin and LSD both