Glossary

A

Addiction. Loss of control over drug use or the compulsive seeking and taking of drug despite adverse consequences.

Amygdala. A brain region particularly important for conditioned forms of learning. This region is critical for establishing associations between aversive and rewarding stimuli and environmental cues.

B

Basal Transcription Complex. A complex comprised of RNA polymerase (which transcribes the new RNA strand) and numerous regulatory proteins (some of which unwind nucleosomes via histone acetyl transferase activity).

Brain Derived Neurotrophic Factor (BDNF). A type of neurotrophic factor which regulates neuronal growth, survival, and function during development and in the adult brain.

Brain reward regions. Areas of brain that mediate the rewarding effects of naturally rewarding stimuli, such as food, sex, and social interactions.

Brain stimulation reward. A behavioral test where animals work to deliver electrical current directly into certain brain regions. Brain reward regions support such intra-cranial self-stimulation. Drugs of abuse reduce the threshold current that animals will deliver, that is, they promote brain stimulation reward, whereas drug withdrawal states do the opposite.

C

Chromatin. The material inside a cell nucleus, including every neuron's nucleus, containing DNA—the basis of heredity—bound to a range of histones and non-histone proteins.

Chromatin immunoprecipitation (ChIP). A method that enables identification of histone modifications or transcriptional regulatory proteins at a given gene promoter. In the assay, DNA is cross-linked to nearby proteins by light fixation, the material is sheared, then immunoprecipitated with an antibody to a particular protein of interest, and genes in the final immunoprecipitate are quantified by PCR.

ChIP -Seq. A method that enables a global analysis of genes associated with a particular histone modification or transcriptional regulatory protein. In the method, immunoprecipitated chromatin is subjected to high throughput sequencing.

Conditioned place preference. A behavioral test where animals learn to prefer an environment associated with rewarding drug administration. It provides an indirect measure of drug reward.

CREB (cAMP Response Element Binding Protein). A type of transcription factor implicated in learning and memory, depression, and drug addiction.

D

Dendritic spine. A small protrusion from a neuron's dendrite that is typically associated with synaptic input from a glutamatergic axon at its tip, but which may receive other inputs (such as dopamine) along its sides or neck.

DNA methyltransferases (DNMTs). Enzymes that methylate DNA.

Dependence. An altered physiological state that develops to compensate for persistent drug exposure and that gives rise to a withdrawal syndrome upon cessation of drug exposure. Dependence may contribute to the dysphoria (negative or aversive emotional state) and high rates of relapse seen during early phases of withdrawal.

Depression. A mental state of depressed mood characterized by feelings of sadness, despair and discouragement. Depression ranges from normal feelings of the blues through dysthymia to major depression. Symptoms of depression include sadness, inactivity, difficulty in thinking and concentration, a significant increase or decrease in appetite and time spent sleeping, feelings of dejection and hopelessness, and sometimes suicidal tendencies.

Dorsal raphia. This 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.

Drug Addiction. See Addiction.

Dysphoria. Negative or aversive emotional state.

E

Epigenome. The compilation of complex types of chromatin modifications that, when overlaid with an individual's genome sequence, determine the degree to which all genes in an organism are expressed (transcriptome). Each cell type in an organism has its own particular epigenome.w

Euchromatin. The activated state of chromatin, in which sections of DNA are accessible to the transcriptional machinery.

F

ΔFosB. A type of transcription factor that appears to play an important role in drug addiction. It is unique due to its prolonged stability.

Frontal cortex. Frontal regions of cerebral cortex, which mediate executive functions and exert control over the subcortical structures that are targets of natural and drug rewards as well as of stressful situations. Such regions include the medial prefrontal cortex, anterior cingulate cortex, and orbitofrontal cortex.

G

GABA. Short for gamma-amino-butryic acid, GABA is the major inhibitor neurotransmitter in brain.

Glutamate. The major excitatory neurotransmitter in brain.

G proteins. GTP-binding membrane proteins that couple many extracellular receptors to intracellular effector proteins.

H

Heterochromatin. The inactivated state of chromatin, in which DNA is not accessible for transcription due to covalent modifications of histones, methylation of the DNA, and the binding of numerous repressor proteins.

Hippocampus. This region is critical for declarative memory, the memory of persons, places, and things. Along with the amygdala, it establishes memories of drug experiences which are important mediators of relapse. It may also contribute to cognitive abnormalities seen in depression.

Histones. Highly basic proteins that comprise the major protein constituents of the nucleus. Octomeric complexes of histones, around which DNA is wrapped, form the nucleosome, the basic building block of chromatin.

Histone acetyltransferases (HATs). Enzymes that catalyze the acetylation of histones.

Histone deacetylases (HDACs). Enzymes that catalyze the deacetylation of histones.

Histone demethylases (HDMs). Enzymes that catalyze the demethylation of histones.

Histone methyltransferases (HMTs). Enzymes that catalyze the methylation of histones.

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

L

Limbic system. A collection of cortical and subcortical structures important for processing memory and emotional information. Prominent structures include the hippocampus, amygdala, prefrontal cortex, and nucleus accumbens, among others.

Long-term depression and potentiation. Key forms of synaptic plasticity in the brain which are greatly influenced by drugs of abuse.

Locus coeruleus. This 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. The locus coeruleus is located on the floor of the fourth ventricle in the anterior pons. It also is an important mediator of physical dependence on opiates.

M

Medium spiny neurons (MSNs). The main neuronal cell type in nucleus accumbens and dorsal striatum; these GABAergic projection neurons form the two main outputs of these structures, called the direct (D1-type MSNs) and indirect (D2-type MSNs) pathways.

Motivation. Those factors which cause an organism to behave or act in either a goal-seeking or satisfying manner. They may be influenced by physiological drives or by external stimuli.

N

Neurophysiology. This experimental approach utilizes a series of advanced tools which make it possible to record the electrical activity of neurons both in brain slices and from alive animals in vivo.

Neurons - or - nerve cell. A cell specialized to transmit electrical nerve impulses. A typical neuron consists of dendrites (fibers that receive stimuli and conduct them inward), a cell body (a nucleated body that receives input from dendrites), and an axon (a fiber that relays the nerve impulse from the cell body outward to its terminals, the synaptic knobs). Impulses are conducted by neurotransmitter chemicals released by the axon's synaptic endings across the synapses (junctions between) or, in some cases, pass directly from one neuron to the next.

Neurotransmitter. A substance released from the axon terminal or ending of a presynaptic neuron to either excite or inhibit a target cell. Examples of neurotransmitters include: glutamate, GABA ( g -amino-butyric acid), dopamine, serotonin, acetylcholine, norepinephrine, epinephrine (adrenaline), glycine, substance P, and enkephalin.

Neurotrophic Factor. Nerve growth factors that regulate the birth and survival of neurons during development and modify their functioning and survival in the adult brain. Neurotrophins are a major type of neurotrophic factor, an example of which is BDNF (Brain Derived Neurotrophic Factor).

Norepinephrine (noradrenaline). Catecholamine neurotransmitter, used by the sympathetic nervous system and in the brain.

Nucleosome. A tightly wound span of DNA that is bound to histones and other nuclear proteins. Transcription of a gene requires the unwinding of a nucleosome, which makes the gene accessible to a basal transcription complex.

Nucleus Accumbens (NAc). Also called ventral striatum, this region is a principle target of VTA dopamine neurons and mediates the rewarding effects of natural rewards and drugs of abuse. Together, the VTA-NAc pathway, also called the mesolimbic dopamine system, is the most important reward circuit in brain. It is also highly responsive to stress.

O

Opioid. Originally, a term denoting synthetic narcotics resembling opiates but increasingly used to refer to both opiates and synthetic narcotics.

Optogenetics. Recently developed tools that make it possible to control the activity of neurons, or the activity of individual proteins within neurons, with light, which is applied to a particular brain region of interest via a fiber optic cable.

P

Protein phosphorylation. A process wherein phosphate groups are added to proteins by protein kinases or removed from proteins by protein phosphatases. The addition or removal of phosphate groups dramatically alters protein function and leads to the myriad of biological responses in question.

R

Reinforcing Stimulus. A stimulus that increases the probability that behaviors paired with it will be repeated.

Reward. A stimulus that the brain interprets as intrinsically positive, or as something to be approached.

Reward Regions. Regions of the brain that mediate reward and reinforcement. See Amygdala, Dorsal Raphe, Frontal Cortex, Hippocampus, Hypothalamus, Locus Coeruleus, Nucleus Accumbens, and Ventral Tegmental Area.

S

Second Messengers. Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. Second messengers include cAMP [cyclic AMP], calcium, phosphatidylinositol, and nitric oxide.

Self-administration. A form of operant conditioning using a drug as a reward, generally by administration through an intravenous line that is controlled directly by the animal's actions.

Sensitization. Enhanced drug responsiveness with repeated exposure to a constant dose. May be referred to as a reverse tolerance. Sensitization may contribute to the increased risk of relapse after longer withdrawal periods.

Sirtuins. Categorized as Class III histone deacetylases, but serve as protein deacetylases for many non-histone proteins as well as part of transcription repressive complexes apparently independent of catalytic activity.

Synaptic plasticity. Processes by which the activity of synapses is controlled by prior use of those synapses. Synaptic plasticity is thought to be a key mechanism of learning and memory and has been implicated in addiction.

T

Tolerance. Reduced drug responsiveness with repeated exposure to a constant drug dose. Tolerance may contribute to the escalation of drug intake seen during the development of an addiction.

Transcription factors. Proteins that bind to specific sites (response elements; also called promoter or enhancer elements) present within the regulatory regions of certain genes and thereby increase or decrease the rate at which those genes are transcribed. Transcription factors act by enhancing (or inhibiting) the activity of the basal transcription complex, in some cases by altering nucleosomal structure through changes in histone acetyl transferase or distone deacetylase activity of the complex.

Transcriptome. The complete assessment of all RNAs and proteins expressed by an individual. Each cell type has its own particular transcriptome.

V

Ventral Tegmental Area (VTA). Located in the ventral midbrain, this is the site of dopaminergic neurons, which tell the organism whether an environmental stimulus (natural reward, drug of abuse, stress) is rewarding or aversive. These neurons are also highly responsive to stress.


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