Biogenic Amines The biosynthetic pathway for the catecholamine

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

Nucl. Prefrontal accumbens CTX

Nigrostriatal Mesolimbic pathway pathway

Substrantia nigra of

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 : - 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 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 synthesis 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