Anhedonia. Decreased interest in, and ability to experience, pleasure. A common symptom of depression.

BDNF (brain derived neurotrophic factor). A major nerve growth factor in brain, which regulates depression-like behavior in the VTA-NAc as well as in other brainn regions.

Brain reward regions. Regions of the brain that regulate an individual’s responses to natural rewards. These regions are also the cites in brain where drugs of abuse act to cause addiction. The VTA-NAc are the major reward regions of brain.

Chromatin. The major contents of the cell’s nucleus, composed primarily of DNA, histones, and other proteins.

Chromatin immunoprecipitation. Experimental technique used to study chromatin structure at genes regulated by stress, antidepressants, or other stimuli.

Cortisol. The major stress hormone in the body, secreted by the adrenal glands. It is under control of the hypothalamus and pituitary gland.

CREB (cAMP response element binding protein). A major transcription factor in brain, which regulates depression-like behavior in the VTA-NAc as well as in other brain regions.

Cyclic AMP (cAMP). A major second messenger in brain, which produces most of its physiological effects by activating a particular type of protein kinase, called cyclic AMP-dependent protein kinase or protein kinase A.

DeltaFosB (∆FosB). A Fos family transcription factor which is induced uniquely in brain reward regions by virtually all drugs of abuse and serves to promote drug use. Due to its unusual stability, ∆FosB persists in brain long after cessation of drug use.

DNA expression arrays. Also called “DNA chips”, these arrays make it possible to study changes in messenger RNA levels for thousands of genes in a relatively high throughput manner.

Dorsal raphe. This region is the primary site of serotonergic neurons in the brain, which, like noradrenergic neurons, pervasively modulate brain function to regulate the state of activation and mood of the organism.

Frontal cortex. These regions are probably the most important, but least understood, and include frontal regions of cerebral cortex, such as medial prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex, which provide executive control over choices made in the environment (for example, whether to seek a reward).

G proteins. Proteins that tranduce the actions of a neurtransmitter, acting on a receptor located on the outside of a neuron, into the interior of the cell, where intracellular signaling pathways are activated.

Gene expression. Processes that control the expression of genes in cells. Selective expression of the body’s 30,000 genes is critical during development to form different organs. More subtle regulation of gene expression occurs in brain throughout life and mediates long-lived changes in behavior, both good (e.g., learning, antidepressant responses) and bad (e.g., depression, addiction).

Hippocampus. This region is critical for declarative memory, the memory of persons, places, or things.

Histones. Families of proteins in the cell’s nucleus that regulate gene expression.

Histone acetytransferases (HAT’s). Enzymes that activate gene expression by adding acetyl groups to histones.

Histone deacetylases (HDAC’s). Enzymes that inhibit gene expression by removing acetyl groups from histones.

Hypothalamus. This region is important for coordinating an individual’s interest in rewards with the body’s physiological state. This region integrates brain function with the physiological needs of the organism.

Intracranial self-stimulation. Rodents will work (press a lever) to pass electric current into specific brain areas, including the VTA-NAc circuit. A change in the threshold current for self-stimulation is reported to provide a measure of affective state, with an increase in threshold current reflecting a depressed affect.

Locus coeruleus. This region is the primary site of noradrenergic neurons in the brain, which pervasively modulate brain function to regulate the state of activation and mood of the organism.

Mesolimbic dopamine system. This describes a neural circuit arising in dopaminergic neurons of the VTA and their projections to the forebrain, in particular, the NAc.

MicroRNA (miRNA). Small RNA’s found in cells that inhibit specific messenger RNA’s. Experimentally, small inhibitory RNA’s (called RNAi’s) can be used to knockdown levels of a messenger RNA in the brain.

NAc (nucleus accumbens). Also called ventral striatum, the NAc is a principle target of VTA dopamine neurons. This region mediates the rewarding effects of natural rewards and drugs of abuse.

Nucleosomes. The major organizational unit of chromatin in which DNA strands are wrapped around complexes of histones and other proteins to form individual units. The DNA strands must unwind in order to be active, that is, transcribed into messenger RNA’s and proteins.

Phosphorylation. A chemical process by which protein kinases add phosphate groups to proteins, a process reversed by protein phosphatases. Phosphate groups, because of their large size and charge, alter the function of the proteins.

Protein kinases. Critical enzymes in the brain’s intracellular signaling pathways that regulate other proteins by phosphorylating them (i.e., adding phosphate groups).

Protein phosphatases. Critical enzymes in the brain’s intracellular signaling pathways that regulate other proteins by dephosphorylating them (i.e., removing phosphate groups).

Relapse. Return to drug use after periods of abstinence, relapse is one of the most challenging features of drug addiction in human populations. Self-administration assays can be used to model relapse in animals, where stress, drug-associated cues, or the drug itself can promote relapse, as seen in human addicts.

Second messengers. Small molecules that form part of the brain’s intracellular signaling pathways that mediate the actions of neurotransmitters and growth factors. Examples include cyclic AMP (cAMP) and calcium.

Self-administration. Model where animals work (e.g., press a lever) to give themselves injections of a drug of abuse. Under the right circumstances, most animals will over time come to self-administer these drugs compulsively.

TrkB. Receptor for BDNF. TrkB works by having protein tyrosense kinase activity which is activated upon BDNF binding.

VTA (ventral tegmental area). The site of dopaminergic neurons, which tell the organism whether an environmental stimulus (natural reward, drug of abuse, stress) is rewarding or aversive.