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Neuromodulator Manipulations and abuses. Natural neuromodulators can aid the release or inhibit the reabsorption of neurotransmitters; still others delay the breakdown after reabsorption, leaving them in the tip to be reused by the next nerve impulse. Mood, pleasure, pain, and other mental states are determined by particular groups of neurons in the brain that use special sets of neurotransmitters and neuromodulators. For example, mood is strongly influenced by the neurotransmitter serotonin. It is believed that depression results from a shortage of serotonin. It is difficult to treat depression directly with serotonin because the chemical has too many other side effects. However, depression can be successfully treated with drugs that act as serotornin neuromodulators (Figure 02d). Prozac, the

Figure 02d Neuromodulator
[view large image]

world's top-selling antidepressant, inhibits the reabsorption of serotonin, increasing the amount in the synapse by slowing down its removal.

 
Drug Addiction When a neuron cell is exposed to a neurotransmitter for a prolonged period, it tends to lose its ability to respond to the stimulus with its original intensity. This is known as habituation, which is the result of the cell producing fewer receptors for that particular neurotransmitter. If someone takes a drug that acts as a neuromodulator (such as cocaine), which causes abnormally large amounts of neurotransmitter (dopamine in this case, Figure 02e) to remain in the synapses for long periods of time, it would generate more pleasure messages. Such action reduces the number of receptors in the neuron. Next time a higher dosage is required to maintain the pleasurable sensation. The result is addiction. Cocaine is a stimulant discovered in the mid-1800s. Many physicians at first considered it a miracle drug, prescribing it for all sorts of physical and mental ailments; it was even added to soft drinks. Today United States law forbids the importation, manufacture, and use of cocaine for nonmedical purposes, and even the medical use is extremely limited.

Figure 02e Drug Addiction
[view large image]

 
Types of Neurotransmitter Neurotransmitters can be broadly classified into two groups - the "classical", small molecule neurotransmitters and the relatively larger neuropeptide neurotransmitters. The small molecule types are mainly amino acids and amines (a nitrogen atom bonds to a maximum of three hydrocarbon groups). The larger neurotransmitters are combination of two or more amino acids joined by peptide bonds. Some fifty different neurotransmitters have been identified. The form of receptors for the neurotransmitters varies depending on the location in the body and produces different physiologic symptom. Understanding the numerous neurotransmitters, their receptors, locations and interactions with one another has been central to the design of medicines for mental illness. Figure 02f shows the effects of three major neurotransmitters and the mental states induced by their interactions.
Table 01 summarizes the properties of some important neurotransmitters.

Figure 02f Types of Neuro-transmitter [view large image]

 
Name Type Postsynaptic Effect Location(s) Function(s)
Dopamine Amine Excitatory Brain, smooth muscle Control arousal levels
Serotonin Amine Excitatory Brain, smooth muscle Effects on mood, sleep, pain, appetite
Noradrenaline Amine Excitatory Brain, smooth muscle Induce arousal, heighten mood
Acetylcholine (ACh) Acetic acid Excitatory & Inhibitory Parasymathetic nervous system, brainstem Role in memory, vasodilation
GABA amino acid Inhibitory Brain Control anxiety level
Enkephalin (opiate) Neuropeptide Inhibitory Brain, spinal cord Reduce stress, promote calm, natural painkiller

Table 01 Neurotransmitters

GABA stands for gamma aminobutyric acid, which is synthesized from glutamate by organisms.

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