Preface Chapter 1. Principles of Pharmacology Pharmacology: The Science of Drug Action Placebo effect Box 1.1. Pharmacology in Action: Naming Drugs Pharmacokinetic Factors Determining Drug Action Methods of drug administration influence the onset of drug action Multiple factors modify drug absorption Drug distribution is limited by selective barriers Depot binding alters the magnitude and duration of drug action Biotransformation and elimination of drugs contribute to bioavailability Therapeutic Drug Monitoring Box 1.2. Pharmacology in Action: Interspecies Drug Dose Extrapolation Pharmacodynamics: Drug-Receptor Interactions Box 1.3. Pharmacology in Action: Drug Categories Extracellular and intracellular receptors have several common features Dose-response curves describe receptor activity The therapeutic index calculates drug safety Receptor antagonists compete with agonists for binding sites Biobehavioral Effects of Chronic Drug Use Repeated drug exposure can cause tolerance Chronic drug use can cause sensitization Pharmacogenetics and Personalized Medicine in Psychiatry Chapter 2.

Structure and Function of the Nervous System Cells of the Nervous System Neurons have three major external features Box 2.1. The Cutting Edge: Embryonic Stem Cells Characteristics of the cell membrane are critical for neuron function Glial cells provide vital support for neurons Box 2.2. Of Special Interest: Astrocytes Electrical Transmission within a Neuron Ion distribution is responsible for the cell''s resting potential Local potentials are small, transient changes in membrane potential Sufficient depolarization at the axon hillock opens voltage-gated Na+ channels, producing an action potential Drugs and poisons alter axon conduction Organization of the Nervous System Box 2.3. The Cutting Edge: Finding Your Way in the Nervous System The nervous system comprises the central and peripheral divisions CNS functioning is dependent on structural features The CNS has six distinct regions reflecting embryological development Box 2.4.

Of Special Interest: Neuroendocrine Response to Stress The cerebral cortex is divided into four lobes, each having primary, secondary, and tertiary areas Rat and human brains have many similarities and some differences Chapter 3. Chemical Signaling by Neurotransmitters and Hormones Chemical Signaling between Nerve Cells Neurotransmitter Synthesis, Release, and Inactivation Neurotransmitters encompass several different kinds of chemical substances Box 3.1. Clinical Applications: Orexin-Based Medications: New Approaches to the Treatment of Sleep Disorders Neuropeptides are synthesized by a different mechanism than other transmitters Neuromodulators are chemicals that don''t act like typical neurotransmitters Classical transmitter release involves exocytosis and recycling of synaptic vesicles Lipid and gaseous transmitters are not released from synaptic vesicles Several mechanisms control the rate of neurotransmitter release by nerve cells Neurotransmitters are inactivated by reuptake and by enzymatic breakdown Neurotransmitter Receptors and Second-Messenger Systems There are two major families of neurotransmitter receptors Second messengers work by activating specific protein kinases within a cell Tyrosine kinase receptors mediate the effects of neurotrophic factors Pharmacology of Synaptic Transmission Synaptic Plasticity The Endocrine System Endocrine glands can secrete multiple hormones Mechanisms of hormone action vary Why is the endocrine system important to pharmacologists? Box 3.2. Pharmacology in Action: Sex Hormones and Drug Abuse Chapter 4. Methods of Research in Psychopharmacology Research Methods for Evaluating the Brain and Behavior TECHNIQUES IN BEHAVIORAL PHARMACOLOGY Evaluating Animal Behavior Animal testing needs to be valid and reliable to produce useful information A wide variety of behaviors are evaluated by psychopharmacologists Box 4.1.

Pharmacology in Action: Using the Three-Chamber Social Interaction Test Box 4.2. Clinical Applications: Drug Testing for FDA Approval TECHNIQUES IN NEUROPHARMACOLOGY Multiple Neurobiological Techniques for Assessing the CNS Stereotaxic surgery is needed for accurate in vivo measures of brain function Neurotransmitters, receptors, and other proteins can be quantified and visually located in the CNS New tools are used for imaging the structure and function of the brain Genetic engineering helps neuroscientists to ask and answer new questions Box 4.3. Pharmacology in Action: Transgenic Model of Huntington''s Disease Behavioral and neuropharmacological methods complement one another Chapter 5. Catecholamines Catecholamine Synthesis, Release, and Inactivation Tyrosine hydroxylase catalyzes the rate-limiting stepin catecholamine synthesis Catecholamines are stored in and released from synaptic vesicles Catecholamine inactivation occurs through the combination of reuptake and metabolism Organization and Function of the Dopaminergic System Two important dopaminergic cell groups are found in the midbrain Ascending dopamine pathways have been implicated in several important behavioral functions Box 5.1. Clinical Applications: Mutations That Affect Dopamine Neurotransmission There are five main subtypes of dopamine receptors organized into D1- and D2-like families Dopamine receptor agonists and antagonists affect locomotor activity and other behavioral functions Box 5.

2. The Cutting Edge: Using Molecular Genetics to Study the Dopaminergic System Organization and Function of the Noradrenergic System Norepinephrine is an important transmitter in both the central and peripheral nervous systems Norepinephrine and epinephrine act through alpha- and beta-adrenergic receptors The central noradrenergic system plays a significant role in arousal, cognition, and the consolidation of emotional memories Several medications work by stimulating or inhibiting peripheral adrenergic receptors Chapter 6. Serotonin Serotonin Synthesis, Release, and Inactivation Serotonin synthesis is regulated by enzymatic activity and precursor availability Similar processes regulate storage, release, and inactivation of serotonin and the catecholamines Box 6.1. History of Psychopharmacology: "Ecstasy"--Harmless Feel-Good Drug, Dangerous Neurotoxin, or Miracle Medication? Organization and Function of the Serotonergic System The serotonergic system originates in the brainstem and projects to all forebrain areas The firing of dorsal raphe serotonergic neurons varies with behavioral state and in response to rewards and punishments There is a large family of serotonin receptors, most of which are metabotropic Multiple approaches have identified several behavioral and physiological functions of serotonin Box 6.2. The Cutting Edge: Serotonin and Aggression Chapter 7. Acetylcholine Acetylcholine Synthesis, Release, and Inactivation Acetylcholine synthesis is catalyzed by the enzyme choline acetyltransferase Many different drugs and toxins can alter acetylcholine storage and release Acetylcholinesterase is responsible for acetylcholine breakdown Box 7.

1. Pharmacology In Action: Botulinum Toxin--Deadly Poison, Therapeutic Remedy, and Cosmetic Aid Organization and Function of the Cholinergic System Cholinergic neurons play a key role in the functioning of both the peripheral and central nervous systems Box 7.2. The Cutting Edge: Acetylcholine and Cognitive Function There are two acetylcholine receptor subtypes: nicotinic and muscarinic Chapter 8. Glutamate and GABA GLUTAMATE Glutamate Synthesis, Release, and Inactivation Neurons generate glutamate from the precursor glutamine Glutamate packaging into vesicles and uptake after release are mediated by multiple transport systems Organization and Function of the Glutamatergic System Glutamate is the neurotransmitter used in many excitatory pathways in the brain Both ionotropic and metabotropic receptors mediate the synaptic effects of glutamate Box 8.1. Clinical Applications: Fragile X Syndrome and Metabotropic Glutamate Receptor Antagonists: A Contemporary Saga of Translational Medicine AMPA and NMDA receptors play a key role in learning and memory High levels of glutamate can be toxic to nerve cells GABA GABA Synthesis, Release, and Inactivation GABA is synthesized by the enzyme glutamic acid decarboxylase GABA packaging into vesicles and uptake after release are mediated by specific transporter proteins GABA is coreleased with several other classical neurotransmitters Organization and Function of the GABAergic System Some GABAergic neurons are interneurons, while others are projection neurons The actions of GABA are primarily mediated by ionotropic GABAA receptors Box 8.2.

Clinical Applications: GABA and Epilepsy GABA also signals using metabotropic GABAB receptors Chapter 9. Drug Abuse and Addiction Introduction to Drug Abuse and Addiction Drugs of abuse are widely consumed in our society Drug use in our society has increased and has become more heavily regulated over time Features of Drug Abuse and Addiction Drug addiction is considered to be.