Neurotransmiter and neurotransmodulator

Neurons are responsible for most of the information transmitted from place to place within the brain. In
the brain most synaptic communication is accomplished by two neurotransmitters: one with excitatory
effects (glutamate) and one with inhibitory effects (GABA). Most of the activity of local circuits of
neurons involves balances between these chemicals. And with the exception of neurons that detect
painful stimuli, all sensory organs transmit information to the brain through axons whose terminals
release glutamate.

Neurotransmitters other than glutamate and GABA tend to activate or inhibit entire circuits of neurons
that are involved in particular brain functions. For example, secretion of acetylcholine activates the
cerebral cortex and facilitates learning, but the information that is learned and remembered is
transmitted by neurons that secrete glutamate. Secretion of dopamine in some regions generally
activates voluntary movements but does not specify which movements will be activated.

Peptides

Numerous different peptides are released by central nervous system neurons. Peptide molecules are
made up of two or more amino acids connected by peptide bonds. Precursor molecules are used to
create all of the peptides that have been investigated to date. Large polypeptides that make up these
precursors are fragmented by specialized enzymes. The polypeptides and the enzymes required to
disassemble them precisely where they are needed are both produced by neurons. The necessary
polypeptide segments are kept, while the rest is removed. Peptide synthesis occurs in the soma, thus
vesicles carrying these compounds must be transported by axoplasmic transport to the terminal
buttons.

Only a subset of the molecules are released into the synaptic cleft because peptides are released from
all regions of the terminal button, not only the active zone. The remaining ones apparently interact with
nearby cells' receptors. Peptides are degraded by enzymes after they are released. There is no
mechanism for reuptake and recycling of peptides.

Neurons release an assortment of peptides. Some peptides function as neurotransmitters, even though
the majority seem to work as neuromodulators. The endogenous opioid family of peptides is one of the
most well-known. Endogenous means "made from within," and opioid refers to something akin to
opium. According to studies, opiates (drugs like opium, morphine, and heroin) lessen pain because they
have an immediate impact on the brain.

When opiate receptors are triggered, several different brain systems are brought into action. One kind
relieves pain, another prevents species-specific defensive behaviors like hiding and running, and a third
type activates a network of neurons involved in reinforcement. The final result clarifies why opiates are
frequently abused. . The situations that cause neurons to secrete endogenous opioid.
Two separate types of synaptic vesicles, each containing a distinct chemical, are present in terminal
buttons. Peptides are released from these terminal buttons together with a neurotransmitter.

Several peptide hormones released by endocrine glands are also found in the brain, where they serve as
neuromodulators. In some cases the peripheral and central peptides perform related functions. For
example, outside the nervous system the hormone angiotensin acts directly on the kidneys and blood
vessels to produce effects that help the body cope with the loss of fluid, and inside the nervous system
circuits of neurons that use angiotensin as a neurotransmitter perform complementary functions,
including the activation of neural circuits that produce thirst. The existence of the blood–brain barrier
keeps hormones in the general circulation separate from the extracellular fluid in the brain, which
means that the same peptide molecule can have different effects in these two regions.

Lipid

Various substances derived from lipids can serve to transmit messages within or between cells; the best
known, and probably the most important, are the endocannabinoids. These are natural ligands for the
receptors that are responsible for the physiological effects of the active ingredient in marijuana. THC
(tetrahydrocannabinol, the active ingredient of marijuana) stimulates cannabinoid receptors located in
specific regions of the brain. Two types of cannabinoid receptors, CB1 and CB2, both metabotropic, have
since been discovered. CB1 receptors are found in the brain's frontal cortex, anterior cingulate cortex,
basal ganglia, cerebellum, hypothalamus, and hippocampus. CB2 receptors are outside the brain,
especially in cells of the immune system. THC induces analgesia and drowsiness, increases appetite,
lessens nausea brought on by cancer treatment medications, calms asthma attacks, lowers eye pressure
in glaucoma patients, and lessens the symptoms of some motor diseases. THC, on the other hand,
interferes with memory and attention, changes how you see and hear, and affects how you perceive the
passing of time.

Anandamide doesn't appear to be stored in synaptic vesicles; rather, it appears to be created and
released as needed. An enzyme called FAAH (fatty acid amide hydrolase), which is found in anandamide-
secreting neurons, deactivates it. Anandamide transporters are responsible for returning anandamide
molecules to these neurons because the enzyme is located there. Other than THC, a number of
medications have been found to have an impact on how the endocannabinoids function. Rimonabant,
an inhibitor of FAAH, MAFP, and AM1172, an inhibitor of reuptake, all block CB1 receptors.

CB1 receptors are presynaptic heteroreceptors that control neurotransmitter release and can be present
on the terminal buttons of glutamatergic, GABAergic, acetylcholinergic, noradrenergic, dopaminergic,
and serotonergic neurons. The receptors in the terminal buttons open potassium channels when they
are triggered, reducing the duration of action potentials there and the amount of neurotransmitter
released. When neurons release cannabinoids, the chemicals spread out over an area of around 20 m
and remain active for several tens of seconds. THC appears to act on CB1 receptors in the hippocampus
to generate the short-term memory impairment that comes along with marijuana usage. A specific
mutation that blocks the development of CB1 receptors eliminates the reinforcing effects of morphine
but not those of cocaine, amphetamine, or nicotine, suggesting that endocannabinoids also play a
crucial role in the reinforcing effects of opiates.