Catecholamines and Actions of Psychomotor Stimulants

This set explores the synthesis, synaptic mechanisms, and neuroanatomical pathways of catecholamines, specifically focusing on the actions and behavioral effects of psychomotor stimulants like cocaine and amphetamine.

Catecholamines

A subcategory of monoamines that includes Dopamine, Norepinephrine, and Epinephrine.

Indolamines

A subcategory of monoamines that includes Serotonin ($5 ext{-HT}$).

Tyrosine hydroxylase (TH)

The rate-limiting enzyme in catecholamine synthesis that converts L-Tyrosine to L-DOPA.

Arvid Carlsson

Nobel Prize winner ($2000$) who demonstrated that dopamine exists in specific brain parts and functions as a neurotransmitter, rather than just a precursor for Norepinephrine.

VMAT2

The protein responsible for packaging all monoamines into vesicles in the brain.

Monoamine oxidase (MAO)

The enzyme responsible for the degradation of monoamines.

D1 class receptors

Dopamine receptors (D1 and D5) coupled to stimulatory G proteins ($G_{ ext{s}}$) that increase adenylate cyclase activity and $cAMP$ levels.

D2 class receptors

Dopamine receptors (D2, D3, and D4) coupled to inhibitory G proteins ($G_{ ext{i}}$, $G_{ ext{o}}$) that reduce activity; these often function as presynaptic autoreceptors.

Striatum

The major target of dopamine in the brain, consisting of the dorsal striatum (caudate putamen) and the nucleus accumbens.

Nigrostriatal pathway

A dopamine system originating in the substantia nigra ($A9$) and projecting to the dorsal striatum (caudate putamen).

Mesolimbic dopamine system

A dopamine system originating in the ventral tegmental area (VTA/$A10$) and projecting to the nucleus accumbens.

Cocaine

A psychostimulant that blocks monoamine transporters (DAT, NET, and SERT) and acts as a local anesthetic by blocking voltage-gated $Na^+$ channels at high concentrations ($1 ext{mM}$).

Amphetamine

A drug that enhances monoamine release by entering via DAT, inhibiting vesicle storage (VMAT blockade), and forcing dopamine out by making DAT work in reverse.

Pimozide

A dopamine receptor antagonist used to study its effects on amphetamine reward and self-administration.

SSRIs (Selective Serotonin Reuptake Inhibitors)

Selective blockers of SERT, such as fluoxetine (Prozac), which are not commonly abused or self-administered by animals.

Stereotypies

Repetitive, purposeless behaviors produced by drug-enhanced dopamine release specifically in the dorsal striatum.

6-OHDA (6-hydroxy dopamine)

A neurotoxin used to selectively destroy dopamine terminals to study the contribution of specific brain regions to drug action.

MDPV (3,4-methylenedioxypyrovalerone)

A cathinone found in stimulant 'bath salts' that causes more DA release and behavioral activation than cocaine; it was addressed by the Synthetic Drug Abuse Prevention Act of $2012$.

DAT occupancy

The percentage of dopamine transporters bound by a drug; Volkow et al. found that a subjective 'high' requires $40 ext{--}60 ext{\%}$ occupancy by cocaine.