Basic Neurochemistry and Psychopharmacology

Basic Neurochemistry and Psychopharmacology

Channel functions operate primarily with the classical neurotransmitters glutamate, aspartate and GABA. The state functions too operate with these same neurotransmitters, but also with a number of others, such as serotonin and dopamine. The latter terms may be familiar to you because psychopharmacologists work constantly with these neurotransmitters – and herein lies an interesting connection. It is no accident that the most familiar aspects of psychopharmacology deal with these chemicals, which convey the influence on the brain of the internal milieu – the “drives”. What then, are the chemicals that govern the internally directed systems?

The first is the neurotransmitter acetyicholine (Ach), which is employed by a good many neurons throughout the brain. Neurons using this neurotransmitter are called cholnergic neurons, and two such systems are of specific interest. The first cholinergic system arises in the mesopontine tegmentum (part of the reticular formation, in the back half of the pons). These neurons project via the thalamus and influence the cortex in a fairly global way.

Only the cell bodies of these acetyl-choline-producing neurons are found in the brainstem structures of the pontine tegmentum. The axons of these cells extend into sites in the hypothalamus, thalamus, and cerebral cortex, to other cells and modify the firing rates of those cells with Ach having narrow sites of origin (cell bodies clumped together in nuclei) and broad regions to which they project (via their axons) – applies to all the systems. A second (and very important) state-dependent system that employs Ach has its origin in the basal forebrain nuclei. This system, too, globally affects the firing rate of almost the entire cortex.

The next important state-dependent neurotransmitter system has its origins in the raphe nuclei of the brainstem. These neurons produce serotonin (5HT) and deliver it widely in the forebrain. Serotonin is well known for its use in antidepressant medications – the SSRIs (selective serotonin reuptake inhibitors). This phrase allows us to expand slightly our knowledge of cellular neurophysiology. A neurotransmitter is excreted via an axon into the synaptic space, where it attaches to receptors on the next neuron and thereby increases or reduces its firing rate.

Neurotransmitters define our lives. Photo by Elena.

An additional fact is that the neurotransmitter is not lost in the second cell. After a period of time, the neurotransmitter is absorbed back into the first cell, so that it can be reused. This process of retrieving the neurotransmitter back into the first cell, so that it can be reused. This process of retrieving the neurotransmitter is called “reuptake”. SSRIs are reuptake inhibitors, which implies that they slow the process of reabsorbtion or the neurotransmitter back into the first cell. This means that the excreted neurotransmitter is active in the synaptic space for a longer period of time and excites the second neuron accordingly. Any chemical that inhibits reuptake of a neurotransmitter has the effect of rendering the neurotransmitter (in this case, serotonin) more effective by making is longer-lasting.

The third class of neurotransmitter that has its origin in a core brainstem nucleus is called norepinephrine (NE: known as noradrenaline in Britain). This neurotransmitter has its source celles in the nucleus locus coeruleus of the pons. As with other state-dependent systems, the sites of action of this system are extremely diverse.

The last of the neurotransmitters to be mentioned here is produced in a transitional region between the midbrain and the diencephalon called the ventral tegmental area. The neurotransmitter produced by these cells is called dopamine (DA). Dopamine is also produced in other sites in the brainstem, the best-known of which is the substantia nigra (well known due to its role in Parkinson's disease). This nucleus is the source of the nigrostriatal DA system (which projects mainly onto the basal ganglia), but the system that originates in the ventral tegmental area is more important for our purposes. This is called the mesocortical-mesolimbic DA system, because it acts principally on limbic and cortical structures on the medial surfaces of the forebrain. Its main targets are the hypothalamus, nucleus accumbens (a basal-forebrain nucleus nestled beneath the basal ganglia), anterior cingulate gyrus, and amygdala. This system also projects to other structures, including the frontal lobes as a whole.

The neurotransmitters just described (as well as others that we have not discussed, such as histamine, which is sourced mainly in the hypothalamus) are called neuromodulators. This refers to the fact that the state-dependent neurotransmitter systems through which they operate exert global effects, via mass-action, over and above the existing activities of the specific pathways in the channel-dependent systems. They modulate these activities, in response to the current state of the organism. Thus, for example, all cognitive operations are affected – in a relatively global way – by changes in mood, vigilance, and waking state.

The Brain and the Inner World, Introduction to Basic Concepts. Mark Solms, Oliver Turnbull.

Our cognitive operations are affected by changes in mood... Photo by Elena.