Behavioral Neuroscience, lecture on Glutamate
Escape Behavior
VI. Dopamine (DA)
A. Synthesis: catecholamines (DA, NE, Epi)
1. precursor: tyrosine (Tyr or Y)
a. tyrosine hydroxylase
(TH, an oxidase, rate limiting enzyme)
2. L-DOPA (levo-dihydroxyphenylalanine)
a. DOPA decarboxylase (aromatic aa decarboxylase)
3. Dopamine (DA)
a. CO2 released
4. Other Neurons have TH, aaa decarboxylase +
a. dopamine b-hydroxylase (DBH) ® norepinephrine (NE)
b. or DBH + phenylethanolamine-N-methyltransferase (PNMT) ®
® epinephrine (Epi)
B. DA is synthesized in the substantia nigra and ventral tegmental
area of the mesencephalon (midbrain)
1. SN (A9) axons project to the caudate-putamen (striatum)
a. mesostriatal (nigrostriatal) system:
necessary for coordinated movmement
b. degenerate during Parkinson's
2. VTA (A10) axons have mesolimbic projections, ie. to limbic
structures inclucing: amygdala, olfactory tubercle, septal area,
and nucleus accumbens
a. emotion, aggression, reward, salience,
b. mesocortical: prefrontal cortex - cognition
3. short axon DA cells in arcuate nucleus of the hypothalamus (A11-15),
retina, olfactory bulb (A16), superior colliculus of the optic tectum,
retina (A17) and around the 4th ventricle
a. ARC nucleus DA modulates Releasing Hormone secretion
C. Receptors
1. DA1-5 - in two main subgroups
a. DA1 stimulatory (Gs protein stimulates cAMP)
i. DA5 is a subtype of DA1 (Gs)
(1) subtype means very similar: genes + structure
b. DA2 inhibitory (Gi blocks cAMP)
i. DA3 is a subtype of DA2 (Gi high limbic concentrations)
ii. DA4 is also a DA2 subtype (Gi)
D. Degradation and Reuptake
1. most synaptically released DA is recaptured
a. DAT = membrane transporter
(facilitated [Na+] transport)
i. similar to NE and GABA transporters
ii. blocked by cocaine
iii. there is also a VAT (vesicular amine transporter)
to put loose cytoplasmic DA into vesicles
b. reuptake is the main way by which
transmitter function is terminated
c. the rest is catabolized by monoamine oxidase (MAO),
catechol-O-methyltransferase (COMT),
aldehyde dehydrogenase, or aldehyde reductase
d. intraneuronal catabolism produces 3-O-methyl DA
e. synaptic catabolism produces DOPAC
(3,4-dihydroxyphenylacetic acid)