Chapter 1
Introduction to Neuropsychopharmacology

Henry V, IV, iii (William Shakespeare)

(Marcus Tillius Cicero)

1.1 Overview

Neuropsychopharmacology is a relatively new subject area in the neurosciences and may be viewed as the amalgamation of the principals of neuropharmacology and psychopharmacology. Neuropharmacology mainly deals with the effects of drugs on neurones, synapses and brain circuits and their interaction with neurotransmitters and other neurochemicals at their receptors and ion channels, both at a molecular and systems level. Psychopharmacology is the study of drugs that have the ability to alter mental states, such as emotional behaviours and cognition. Neuropsychopharmacology is, therefore, a field of study that describes the effects of drugs from the molecular to the behavioural level and requires integration and synthesis of knowledge from various disciplines, including neuroanatomy, physiology, pharmacology, molecular biology, genetics, psychology, psychiatry, sociology, biochemistry and chemistry. The principals of neuropsychopharmacology are important in (i) discovering more about the workings of the brain and the impact on behaviour, (ii) learning about the cellular, receptor and neurochemical changes that accompany brain dysfunctional states and (iii) the development of drugs to treat central nervous system (CNS) disorders and psychiatric conditions.

The authors of most textbooks on neuropharmacology and psychopharmacology presuppose that the reader has almost no knowledge of basic pharmacology, neurotransmitters and neurotransmission, receptor mechanisms, cell signalling, neuroanatomy, the fundamental principals of molecular biology and genetics. Therefore, they spend the first few chapters of their books explaining the essential principals of these subject areas. Here, on the other hand, I will assume that the reader of this book has a working knowledge of these subjects. However, a lot of the basic information is covered in the different chapters of this book. In this chapter, some of the useful terms and concepts referred to in subsequent chapters are explained and brief overviews are given of (i) the anatomy and functions of the brain, (ii) important neurotransmitters in the CNS, (iii) some of the CNS depressant and stimulant drugs that are used in the treatment of the disorders that are discussed in subsequent chapters, and(iv) the experimental and clinical techniques that are used to obtain information on brain function.

1.2 A Brief Overview of the Anatomy and Function of the Brain

Reviewed briefly in this section are some of the important structures in the brain and their main functions. More detailed information on the anatomy and function of brain areas pertinent to specific CNS disorders are covered in the relevant chapters.

1.2.1 The Brainstem

The brainstem is made up of three structures, the medulla oblongata, the pons and the midbrain (Figure 1.1).

• The Medulla Oblongata (commonly referred to as the medulla) is a division of the brain known as the myelencephalon. It forms the most posterior or lowest part of the brain and is often considered an extension of the spinal cord within the skull. It is a small structure of about one inch (2.5 cm) in length and lies below the pons. It is composed largely of projection tracts carrying information between the body (via the spinal cord) and the rest of the brain. The medulla also has a network of cells that occupy the core of the brainstem, extending through the pons and midbrain, known as the reticular formation (reticulum means 'little net'). The ascending projections from the reticular formation project to the thalamus and cortex and play an important role in arousal and, for this reason, they are also known as the ascending reticular activating system (ARAS) (Chapter 8). Various nuclei in the medulla's reticular formation have diverse functional roles. There are cardiac, vasomotor and respiratory centres that regulate cardiovascular, circulatory and respiratory reflexes, respectively, as well as other nuclei that regulate reflexes, including vomiting, swallowing, coughing and sneezing.
• The Pons (which means bridge) is a structure, with a characteristic bulge, that lies above the medulla and is considered a 'bridge' between the medulla and the midbrain (which is located above it). Ascending and descending fibre tracts pass through the pons, which is also part of the reticular formation. It is a division of the brain known as the metencephalon. It is connected to another division of the metencephalon, the cerebellum (Section 1.2.2), by bundles of transverse fibre tracts. The pons contains centres for reflexes that are mediated by the fifth (trigeminal), sixth (abducens), seventh (facial) and eighth (vestibulocochlear) cranial nerves. The pons also has the pneumotaxic centres that, together with the medulla, control respiration.
• The midbrain is a division of the brain known as the mesencephalon and lies above the pons. Ascending and descending fibre tracts pass through the midbrain and it is also part of the reticular formation. The roof or tectum of the midbrain consists of two pairs of folds called colliculi (meaning 'little hills'); these form the upper part of the midbrain that lies immediately above the cerebellum The two inferior colliculi have auditory centres and are involved in auditory function. The superior colliculi, which lie in front of the inferior colliculi, have visual centres and are involved in the regulation of pupillary reflexes and eye movements that are mediated by the third and fourth cranial nerves, respectively. Under, or ventral to the tectum, is another subdivision of the midbrain, the tegmentum, which contains part of the brainstem reticular formation. In addition, it contains a number of other key nuclei: the periaqueductal grey, which is involved in the regulation of pain and species-specific startle reflexes (Chapter 8); the substantia nigra and the red nucleus, which are involved in the regulation of motor movements (Chapter 2); and nuclei that are involved in the regulation of motivation and reinforcement (Chapters 10 and 11).

Figure 1.1 The human brain.

1.2.2 The Metencephalon

The cerebellum (meaning 'little brain') is a division of the metencephalon (Figure 1.1). It is a highly convoluted structure that has two hemispheres and is located behind the brainstem, to which it is connected. The cerebellum is the second largest part of the brain after the cerebral cortex and occupies about one-tenth of the brain's volume. It is densely packed with neurones and has more than half the total number of neurones in the brain. It can be divided anatomically into three parts, known as the inferior, middle and superior cerebellar peduncles, which carry nerve fibre tracts between the medulla, pons and midbrain, respectively, and the cerebellum. The cerebellar cortex (outer layer) consists of grey matter (cell bodies) and the central core consists of white matter (myelinated nerve fibres). The cerebellar white matter has nerve fibre tracts that run to and from the thalamus and cortex.

The main function of the cerebellum is the coordination of movement; this operates below the level of consciousness. The cerebellum receives incoming sensory information from the ears (equilibrium receptors), skeletal muscles (proprioceptors), the brainstem and the cerebral cortex. It integrates this information and sends it to the motor cortex and skeletal muscle to coordinate posture, balance and movement. The cerebellum also acts, in conjunction with the cortex, to plan motor movements. In addition, the cerebellum has a role in 'storage' and 'execution' of motor memories, such as riding a bicycle or playing the piano, which once learnt can be carried out reflexively without conscious thought. More recently, there has been evidence to suggest that the cerebellum may also have a role in the regulation of cognitive functions, such as nonmotor learning and attention.

Damage to the cerebellum, due to haemorrhage, tumours or injury, may result in ataxia (which is loss of muscle coordination), tremor, vertigo (dizziness), slurred speech and an inability to walk. Drugs, such as alcohol, benzodiazepines and barbiturates (Sections 1.6.1 and 1.6.2; Chapters 9 and 11), may depress neural activity in the cerebellum and produce symptoms such as ataxia and slurred speech.

1.2.3 Diencephalon

The diencephalon (which means 'between brain') is the division of the brain that is located between the cerebral cortex and the midbrain. The main structures of the diencephalon are the thalamus and hypothalamus (Figure 1.1). There are other smaller structures, such as the pineal gland (Chapter 9), in the diencephalon.

• The thalamus is a structure consisting of two large lobes that are situated on each side of the third ventricle (Section 1.2.6) and joined together by the massa intermedia that extends through the ventricle. Fibre tracts carrying sensory and other information from the spinal...