Ch. 5: Catecholamines

Catecholamines

DA, NE, EPI (monoamines)

Tyrosine -(TH)→ DOPA -(AADC)→ Dopamine -(DBH)→ Norepinephrine

Multistep Pathway of Catecholamine Synthesis

Catecholamine storage and release is regulated by

Vesicular uptake, Autoreceptor activity, Cell firing rate

How catecholamines are released

By exocytosis when nerve impulses reach terminal

Single Spiking Mode

Cell generates action potential at irregular intervals, 4-5 Hz

Burst Mode

Excitatory input to cell has trains of 2-20 spikes at a high frequency, 20 Hz

D1 Receptors

Effects on cognition in the PFC, excitatory

D1, D5

D1 Family

D2, D3, D4

D2 Family

D2 Receptors

In pituitary gland, increases DA affinity, act as autoreceptors

Side effect from blocking D2

Lactation

D3 Receptors

In limbic system, regulate emotions and motivation

D4 Receptors

Lowest of all 5 receptors, in frontal cortex, hippocampus, amygdala

D5 Receptors

Increases affinity for DA, in frontal cortex, hippocampus, amygdala

Stimulates Adenylyl Cyclase and increases cAMP synthesis

D1

Inhibits adenylyl cyclase, decreases cAMP synthesis

D2

Apomorphine

Agonist that stimulates D1 and D2, causes behavioral activation

DETQ

Allosteric modulator of D1 receptors, no tolerance development

Norepinephrine

Important in the central and peripheral NS, found in pons, medulla, and locus coeruleus (LC)

LC

Sends fibers to most areas in forebrain, provides NE to many areas of the brain

β1- and β2- receptors

Stimulate adenylyl cyclase and enhance cAMP formation

α2-receptors

Inhibit adenylyl cyclase, reduce cAMP synthesis, increases opening of K+ channels

α1 receptors

Uses phosphoinositide 2nd messenger system

Clonidine

α2-agonist, treats opioid withdrawal symptoms, stimulates α2 Autoreceptors to inhibit noradenergic cell firing

Orexin

Neurons in lateral hypothalamic area, has powerful arousal effects

Propranolol

β-antagonist, treats hypertension by blocking β receptors in heart