Biogenic Amines The biosynthetic pathway for the catecholamine neurotransmitters
08/20/2008 Lerant: Catecholamines 2008 2 Biogenic Amines Synapses
MAO : Monoamine Oxidase Dopamine Dopamine receptors
• G protein-coupled receptors • D1 → excite • D2 → inhibit Mainly presynabtic (Autoreceptor) • D3 → inhibit • D4 → inhibit • D5 → excite 3. Dopaminergic (DA) synapse
08/20/2008 Lerant: Catecholamines 2008 6 Dopamine Pathways DOPAMINERGIC PATHWAYS
Nucl. Prefrontal Striatum accumbens CTX
Nigrostriatal Mesolimbic Mesocortical pathway pathway pathway
Substrantia nigra of midbrain
Ventral tegmental area of midbrain
Lerant: Catecholamines 2008 DOPAMINERGIC PATHWAYS • Degeneration of nigro-striatal DA system Nucl. Prefrontal Striatum and Decreasedaccumbens DAergic CTXtrans-mission in the basal ganglia will lead to Parkinson Disease
Nigrostriatal Mesolimbic Mesocortical pathway pathway pathway
Substrantia nigra of midbrain
Ventral tegmental area of midbrain
Lerant: Catecholamines 2008 DOPAMINERGIC PATHWAYS
Nucl. Prefrontal Striatum accumbens naturalCTX PLEASURE, REWARD AND BEHAVIOR REINFORCING PATHWAY Nigrostriatal Mesolimbic Mesocortical pathway pathway pathway drug-induced
HyperactivitySubstrantiaof nigra mesolimbic pathway: - positiveof midbrain symptoms of schizophrenia
(hallucinations,Ventral etc) tegmental area of midbrain cocaine
Lerant: Catecholamines 2008 DOPAMINERGIC PATHWAYS
PATHWAY INVOLVED IN MOTIVATION Nucl.TO Prefrontal Striatum EXPLORE THE ENVIRONMENT: CURIOSITY,accumbens CTX INTEREST, COGNITIVE FLEXIBILITY, DRIVE FOR SOCIAL ENGAGEMENT.
Relative hypofunction in schizophrenia: Primary mesocortical dopamine deficiency will increase the NEGATIVE SYMPTOMS like Cognitive blunting, social isolation, apathy, anhedonia
Nigrostriatal Mesolimbic Mesocortical pathway pathway pathway
Substrantia nigra of midbrain
Ventral tegmental area of midbrain
Lerant: Catecholamines 2008 Norepinephrine Norepinephrine receptors
Current Nomenclature of • α family Adrenergic Receptor Subtypes
• Β family Noradrenergic (NE) synapse
08/20/2008 Lerant: Catecholamines 2008 14 Norepinephrine Pathway Norepinephrine Pathway
• LC noradrenergic system is highly responsive external stimuli → attention • Learning/memory and seep/wake cycle • Anxiety and stress response • In FRONTAL CORTEX: – Mood regulation → Hypofunction of pathway→Depression NE: Locus Ceruleus ➔ FRONTAL CTX
α2 postsynaptic receptor In FRONTAL CORTEX:
• Attention, working memory, information processing. NE: Locus Ceruleus ➔ FRONTAL CTX
β1 postsynaptic receptor In FRONTAL CORTEX: • Mood regulation.
• Hypofunction of pathway: • Depression Serotonin Serotonin synthesis Serotonin Pathway Serotonin Receptors Serotonin Pathway
Almost 17 type of receptor Wide spread
mood, sleep, sexuality, impulsivity, aggression, stress, drug abuse Serotonin Pathway
Almost 17 type of receptor Wide spread
Serotonin system dysfunction involve in : Depression, Schizophrenia, OCD, Eating Disorders, Autism