The brain is organized into clusters of neurons that form pathways. These are identified according to the particular release of neurotransmitters at these sites. The monoamine pathways are named the meso-limbic-cortical dopamine pathway, the cholinergic pathway and the noradrenergic pathway. Close examination shows axons belonging to specific pathways travel together from their base located within a region in the brain, spreading as they approach their destination.
For instance the Nigro-striatal dopamine pathway starts in the midbrain and descends toward an area in the forebrain called the striatum. Target neurons belonging to this pathway release dopamine (Green S 1994). Each pathway begins with substances found in the diet. For example Acetylcholine is synthesized from choline which is found in cauliflower and milk. Other sources of Licihin that convert into cholin are egg yolks, liver, soybeans, butter and peanuts.
Phenylalanine and Tyrosine are amino acids found in most protein foods that are precursors to dopamine and noradrenaline. The amino-acid serotonin is able to cross the blood brain barrier via a special transport system This amino acid however shares its transport system with other amino-acids including Phenylalanine which are usually in higher concentrates in the diet (Kalat1998). According to Wurtman (1985), including carbohydrates with the protein brings about the release of insulin which diverts these competing amino-acids to other parts of the body, ensuring a more plentiful supply of Tryptophan to enter the brain hence more serotonin.
So far I have described the biological functioning of neurotransmitters in terms of how they are classified, their synthesis, chemical operation at synapse level and pathway operation. I shall now look at how they effect brain functioning and behaviour depending upon the manifestation or lack of neurotransmitter and the specialization of different receptors within an individual. Each of the monoamine neurotransmitters interacts together or with other transmitters and has many functions. Drugs affecting the brain may be beneficial or harmful to an individual depending on their usage. Most drugs affecting the brain do so by their influence at synapse level. Their role is thought to resemble neurotransmitters by either increasing or decreasing their effects. The term antagonists refer to drugs that block transmitter release conversely agonist drugs mimic or increase their effects.
Drugs affecting the use of dopamine by the body include Amphetamines, Cocaine, Methylphenidate, Ritalin, Nicotine and Morphine. Dopamine is thought to be connected with depression, eating regulations, learning, Parkinson’s, Schizophrenia and sex hormones. According to Sacks (1983) and Zuckerman (1991) Dopamine affects the personality and is related to extraversion and impulsivity.
Schizophrenia was first described by Kraeplin (1913) as a disorder whereby the individual affected suffers from either positive symptoms termed type 1 or negative symptoms termed type 2. Type 1 includes hallucinations, delusions and thought disorders and Type 2 characteristics are decreased speech, lack of drive diminished social interaction and loss of emotional response. According to Jaskiw and Weinbegel
(1992) Individuals with Schizophrenia have normal levels of dopamine, however they have been found to release greater amounts of dopamine with the use of the drug amphetamine than non-schizophrenic individuals Breuer et al (1997). Scientists have discovered the more effective a drug on blocking a dopamine receptor the greater its effect on relieving the positive symptoms of schizophrenia (Crow et al 1982). A side effect of drugs used to treat schizophrenia sometimes produces Parkinson’s disease type symptoms. Parkinson’s is another disorder thought to be associated with dopamine. The dopamine level with Parkinson’s however is depleted. The degeneration of neurons in the region of the brain within the substantia nigra responsible for controlling movement manifest symptoms that include slow movement termed bradykinesia, an inability to move termed akinesis, and rigid limbs, a shuffling gait and a stooped posture. Limited facial expression is also common (Kalat 1998).
Acetylcholine has been shown to be connected with Alzheimer’s, behavioural inhibitions, drinking behaviour, memory and voluntary movement of muscles. The Alzheimer brain reveals that there is major loss of the neurotransmitter acetylcholine. Alzheimer’s manifests as a general loss of intellectual function or severe memory loss. According to Evans et al (1989), 5 percent of the population between the ages of 65-74 are affected compared to 50 percent between the age of 85 and over.
Large proportions of the neurons that die with Alzheimer’s are the largest acetylcholine pathways in the brain running from subcortical regions to the cortex. Research to increase acetylcholine in the brain has so far been found to be ineffective. Research thus performed on animals to see the effect acetylcholine has on memory have shown when animals are given cholinergic blockers, or who have legions to cholinergic pathways the rats showed an impairment to their memory. However further experiments where these rats were then implanted with grafts made up of growing cholinergic neurons taken from rat embryos showed a restoration of memory (Green 1994).
Serotonin plays an active part in attack and escape behaviours, depression, eating regulations, learning, sleep and premenstrual syndrome. Hallucinogenic drugs such s LSD is said to resemble the neurotransmitter serotonin and activate at serotonin synapses. Another drug Mehylenedioxymethamphetamine ( MDMA) stimulates the serotonin synapses in high doses. Both drugs produce a dreamlike state thought to be caused by irregular patterns of stimulation causing abnormal perceptions. Research in rats and monkeys show MDMA also destroys serotonin synapses sometimes permanently (Fischer et al 1995).
One of the treatments of depression is the administration of drugs, which affect the serotonin synapses. According to Nofzinger et al (1993), an individual with depression receives little pleasure from sex, feels sad and helpless, has no energy, feels worthless, may contemplate suicide and has trouble sleeping. Serotonin re-uptake inhibitors prevent the presynaptic neuron from reabsorbing catecholamines or serotonin after releasing them; hence they remain longer in the synaptic cleft. The postsynaptic cell initially continues to stimulate. However Antelman et al (1982) stresses the prolonged stimulation of receptors desensitizes them with the release returning to near normal levels.
Noradrenaline also known as norepinephrine is shown to affect depression, eating, premenstrual syndrome sexual behaviour and the sympathetic nervous system. The major noradrenergic pathways in the human brain are the ventral and dorsal noradrenergic bundles, which are found in the hypothalamus (Kalat1998). Research into obesity and hunger have yielded findings of which noradrenaline have been found to be active in.
Ahlskog and Hoebel (1973) conducted a study by cutting a noradrenergic pathway running from the brainstem to the hypothalamus. A number of the axons making up this pathway travel to the VMH and terminate there releasing noradrenaline. Cutting the axons before they reach the hypothalamus has been found to lead to overeating. Noradrenaline is also believed to play a part in premenstrual syndrome, where along with other transmitter and hormone alterations, noradrenaline decreases causing mood change at certain times of the month (Rosensein et al 1996).
In conclusion it can be seen that the extending knowledge of neurotransmitter functioning has enabled scientists to make profound differences to the lives of many suffering from disorders such as, schizophrenia and depression. Greater understanding of the Alzheimer disorder and Parkinson’s are leading to progressive and new research. New neuroscientific research is addressing many new disorders such as Autism and Allergies (Neuroscience, Arden NC America). A recent English study conducted by a team of researchers (Dr John Zajicek et al 2001- 2004) looks at Cannabinoid use and its effects on muscular stiffness in multiple sclerosis patients. The results of this trial are soon to be published.
In my opinion the journey into the complexity of Neurotransmitter functioning is still at an elementary stage which has enormous scope for new discoveries. Special references should be made to acetylcholine, dopamine, noradrenaline and serotonin. This essay will look at how neurotransmitters interact within the nervous system. Whilst there are over 40 neurotransmitters, for the purpose of this essay I shall focus on how the classical neurotransmitters are synthesized, their effects on human behaviour and how drugs interact within their particular synapse domain.
Neurotransmitters are classified according to their chemical composition. Simon Green uses the following classification. Classical neurotransmitters, Amino acid neurotransmitters and possible transmitters or neuromodulators. Classical neurotransmitters are termed monoamines and include Acetylcholine, Noradrenaline, Dopamine and serotonin. Amino acid transmitters include Glycine, Glutamate and Gaba. The last group Green terms as possible transmitters or neuromodulators, and explains they may help regulate the release of other neurotransmitters rather than use the same transmitter principle.
Neurons within the monoamine classification are named by scientists according to the neurotransmitter they use. Identified in the brain as cholinergic, noradrenergic, dopaminergic and serotonergic. These neurons use acetylcholine, noradrenaline, dopamine and serotonin. The synthesis of synaptic neurotransmitters occurs within the neuron. The table below shows the synthesis of neurotransmitters from the monoamine group. These groups are non-acidic and contain the amine group NH2 which derive from amino acids that have undergone a metabolic change.