Drugs, addiction, and the brain

351 Pages·2015·1 MB·English

by  George F Koob

23
TIONAL VIEWS OANEUROADAPT F ADDICTION
FIGURE 1.8 (A) The d standarpattern of af fective dynamics oduced prby a elatively rnovel unconditioned stimulus.
(B) The d standarpattern of fective afdynamics oduced prby , a equently frepeated familiarrunconditioned stimulus. aken [T
with permission om frSolomon RL. The ocess opponent-prtheory of ed acquirmotivation: the costs of e pleasurand the bene(cid:31)ts of pain.
American Psychologist, 1980, (35), 691(cid:150)712.]
absence. The ee degrof dependence can be equated in an animal model of escalation in ug drintake
with the amount of this negative fect, afwhich may access have that Animals access. olonged prwith
range om frmild discomfort to eme extress, distror it
shself-administration ow cocaine intravenous to
fort efor ficulty difof amount the with equated be may
incerases in cocaine self-administration over
ug, object, etc.(cid:148)ed to do without the drequirr
(Russell MAH. What is dependence? In: ds EdwarG dawyhgsei nvpo erlno ngaecdc e(slso ng-access
(ed) ugs Drand ug DrDependence. Lexington Books, [LgA] for 6 h) compaerd with short-access
Lexington MA, 1976, pp. 182(cid:150)187). (ShA; 1 h access). This differ ential exposuer to
cocaine also has dramatic effects on intracra -
n i esuba fo sgurd lla fo tnemele nommoc yek A nial self-stimulation (ICSS) erwadr thersholds.
lam isnla endooimta lsui gfeor snd yidarrabwer ICSS thersholds porgerssively incerase in LgA
c in no d oiheft ttoaeiarshwih stccneoocsistacnuf rats but not ShAor contorl rats acorss succes -
.n ogiutarrd tdsiipnaiRmda etu ceacnarelotd na sive self-administration sessions (see Chapter
c inodeh eht tsniaga snoitca ekil-ssecorp-tnenoppo 4, Psychostimulants). Elevations in baseline
s t dcee entfe fir s ovnaonnaicpeafhoeemecbuhr ICSS thersholds temporally percede and ae r
(etsa paco cekom sohw e lgni saretfA .9). 1erugiF highcloyre rlatweiedts hc alatceodc aiinnet ake.
ytf ios n t , edeetgtnshunnantoi iobkeonmisacoc Post-session elevations in ICSS erwadr thersh -
eht (cid:148)hgih (cid:147)era yrev dipar aiv eht dekoe mtsuor olds then fail to erturn to baseline levels befoe r
.noi tde aicfrpnotaasRrienl iosm tid,atnediven i the onset of subsequent self-administration
hcihw eht (cid:148)shegsiah e(cid:147)yldric peeadtripsedgis - sessions, theerby deviating moer and moe r
t ndsaolco eils .vf tbeeinfcnlnaoeimjaubcHuosc form contorl levels. The porgerssive elevation
, aot isnt rlernoauoihqpe apeetgssiaybprdussed in erwadr thersholds is associated with a dra-
tnacifingis doolb slevel fo .eniacocs uonevartnI matic escalation in cocaine consumption. After
(cid:148) hsur(cid:147) dipar a( snrettap ralimis secudorp eniacoc escalation occurs, an acute cocaine challenge
.0)1.1 erugi(F )(cid:148)wol(cid:147) desaercni na yb dewollof facilitates brain erwadr ersponsiveness to the
The hypothesis that the compulsive use of same degere as befoer but ersults in higher
perturba-onic chrthe by accompanied is cocaine absolute brain erwadr thersholds in LgArats
tested been has homeostasis d ewarrbrain of tion than i nr aSthsA.
24
FIGURE 1.9 Dysphoric feelings followed
the initial euphoria in experimental subjects
who smoked cocaine paste, although the
concentration of cocaine in the plasma of the
blood remained relatively high. The dyspho-
ria was characterized by , anxietyession, depr
peak The cocaine. e morfor e desira and fatigue,
feelings e werobably preached rshortly e befor
the peak plasma concentration, but the first
psychological ements measure wermade later
than the . plasma The assaytemporal sequence
of the peaks shown cannot be ded egarras
definitive. om [Fran VDyke C, Byck R. Cocaine.
o-Repr128(cid:150)141. (246), 1982, American, Scientific
American Scienti(cid:31)c 1982, ' permission. with duced
eserved.]All rights rInc.
FIGURE 1.10 verage behavioral Aratings after an infusion of cocaine (0.6 mg/kg over 30 s; n = 9). The , ush, rhigh, low
and craving ratings e weraveraged within each category for the subjects who had etable interprcocaine functional magnetic
esonance imaging rdata after ection motion and corrbehavioral . ratings Both time-locked peak ush to rand the peak scanner
high ed occurr3 min post-infusion. Peak low (primary eports rof dysphoria and paranoia) occurr ed 11 min post-infusion.
12ed occurrcraving Peak post-infusion. min es. measurfour the of any on infusion saline the om frfects efeported rsubject No
Ratings obtained for ush, r, high, and lowcraving es measure werhigher in subjects blinded to the 0.6 mg/kg cocaine dose
ed comparwith subjects unblinded to a 0.2 mg/kg cocaine dose. aken with [Tpermission om freiter BrHC, Gollub f eisskofRL, W
Acute SE. Hyman BR, Rosen , TRMathew , JPden RiorDR, Gastfriend HL, Kantor JM, Goodman JD, Berke N, Makris DN, Kennedy RM,
1.]on, 1997, (19), 591(cid:150)61fects of cocaine on human brain activity and emotion. Neuref
ith intravenous Wcocaine self-administration e (Figur1), 1.1bearing a striking esemblance rto
in animal models, such elevations in d ewarr human subjective eports. rThese esults rdem-
eshold thrbegin rapidly and can be observed onstrate that the elevated brain d ewarresh-thr
within a single self-administration session olds following olonged praccess to cocaine fail
25
TIONAL VIEWS OANEUROADAPT F ADDICTION
FIGURE 1.11 Rats (n = 1) 1were allowed to self-administer 10, 20, 40, and 80 injections of cocaine (0.25 mg per injec -
tion), and intracranial self-stimulation thresholds were measured 15 min, 2 h, 24 h, and 48 h after the end of each intrave -
session.self-administration cocaine nous data The levels. baseline of 100% esents eprrplot each in line dotted horizontal The
essed e as exprarthe centage mean of perbaseline intracranial esholds. self-stimulation *thr p < 0.05, ** p < ed 0.01, with compar
baseline; #p < 0.05, ## p < baseline. with ed compar0.01, dose Low A. Markou , GFKoob I, Polis PJ, Kenny om frpermission with aken [T
cocaine self-administration transiently eases incrbut high dose cocaine persistently eases decrbrain d ewarrfunction in rats. opean Eur
oscience, 2003, (17), 191(cid:150)195.]Journal of Neur
to eturn rto baseline levels, thus eating cra opr - d ewarrfunction stability ough thrchanges in
essive elevation grin (cid:147)baseline(cid:148) esholds ICSS thr brain d ewarrmechanisms ( Koob and Le Moal,
new a defining and ovide prdata These point. set 2001). The allostatic state esents eprra onic chr
compelling evidence for brain d ewarrdysfunc- deviation of brain d ewarrset point that is often
and self-administration cocaine escalated in tion not overtly observed while the individual is
ong strsupport for a hedonic allostasis model of actively taking the ug. drThus, the allostatic
ug addiction.dr the does only not that is view ger larget ocess b-pr
with epeated rug drtaking, but the d ewarrset
point om frwhich the ocess a-prand ocess b-pre ar
Allostasis and Neuroadaptation
ed anchorgradually moves d, downwareating cr
e Mor, ecentlyropponent ocess prtheory has e 1.12).an allostatic state (Figur
ocirneurthe of domains the into expanded been - a-luge d ee yrtlecsbsaehiiytuttdsfats oelhlTa
cuitry obiology and of neurug drom addiction fr noit la csi tmfneoehmceole rfuoen nid arrbawer
a physiological An perspective. allostatic model stiucric dna noitavitca fo niarb dnal anomroh
of the brain motivational systems has been opr - r ehtehw nwonknu yltnerruc si tI .sesnopser sserts
posed to explain the persistent changes in moti - siht dezisehtopy hdrawer noitcnufsyd si-gurd
vation that e arassociated with vulnerability to batse ehT .snoitcidda lla ot nommoc dna cificeps -
elapse rin addiction, and this model may gen- n oitatsefin ad mnsanoitcenn olcacimota ndaehsil
eralize to other psychopathologies associated g egn vuiceikitsrata ldt atsuf tsapossmioohlctla
with egulated dysrmotivational systems. Allo - y llacit ier cerkaa tgnu irr edlvoort nsf osodconla
stasis om frthe addiction perspective has been desab no noitalugersyd fo cificepss-nartoruen
defined as the ocess prof maintaining ent appar l artne veh tf ostiucricorue neh tn inoitcnu frettim
26
1.12FIGURE the of extension an illustrating Diagram (1974)Corbit and Solomon motivaof model opponent-process -
tion to outline the conceptual framework of the allostatic hypothesis. Both panels esent eprrthe fective afesponse rto the
The . historyug drprior no with ug dra of experience initial the esents eprrdiagram This op) (Tug. dra of esentation pr ocess a-pr
the and state, mood positive or hedonic positive a esents eprr state. mood negative or hedonic negative the esents eprrocess b-pr
an both of sum a be to gued arbeen has (state) stimulus fective afThe a and ocess a-pr experiences who individual An ocess. b-pr
a positive hedonic mood state om fra ug drof abuse with ficient suftime between e-administering rthe ug dris hypothesized
to etain rthe ocess. a-prIn other ds, woran opriate apprcounteradaptive ocess opponent-pr( ocess) b-prthat balances the acti -
vational ocess process) (a-prdoes not lead to an allostatic state. (Bottom) The changes in the fective afstimulus (state) in an
individual equent epeated with ug drfrruse esent that a eprmay transition rto an allostatic state in d the systems ewarbrain r
and, by extrapolation, a transition to addiction. ocess ent The eturns never b-prapparto rthe original homeostatic e level befor
ug drtaking is einitiated, rthus eating cra eater grand eater grallostatic state in the brain d ewarrsystem. The counteradap -
tive ocess opponent-process) (b-prdoes not balance the activational ocess process) (a-prbut in fact shows esidual resis. hyster
Although these changes e arexaggerated and condensed over time in the esent prconceptualization, the hypothesis is that
even after detoxification during a period of olonged prabstinence, the d ewarrsystem is still bearing allostatic changes. In
the nondependent state, d ewarrexperiences e arnormal, and the brain ess strsystems e arnot eatly grengaged. During the
transition to the state known as addiction, the d brain ewarsystem ris in a major underactivated state while the brain ess str
system is highly activated. The following definitions apply: allostasis, ocess the of prachieving ough stability change; thr allo-
static state, a state of onic chrdeviation of the egulatory rsystem om frits normal (homeostatic) operating level; allostatic load,
and states pathological cases many in eflecting rand time, over accumulating deviation, the of body and brain the to cost the
accumulation of damage. , Le d, Moal and M. ug egulation ewarallostasis. Draddiction, of dysrraken with om permission Koob frGF[T
opsychopharmacology, 2001, (24), 97(cid:150)129.]Neur
. )2 retpahC ees( aladgyma dednetxe dna mutairts YSUMMAR
d eweiv si sdlohserht drawer ni noitavele cinorhC
sa a yek tnemele ni eht tnempoleved focidda - This chapter defines addiction as a onic chr
noit taht stes pu rehto noitaluger-fless eruliaf elapsing rder disorcharacterized by compulsive
dna tnetsisrep ytilibarenluv ot espalerg nirud intake, limiting in ol controf loss a seeking, ug dr
cid dgau rtda hwte iev h.Tecnenits bdaetcartorp - and gence emerof a negative emotional state
s tluser taht ygolohtap eht era msilohocla dna noit when access to the ug dris evented. prThe defi -
ri ceh tsprus utah tmsinahce mcitatsoll an amorf - evolution the om frderived is addiction of nition
n asedivor psdrawe rlaruta nro fdehsilbats estiuc of the concept of dependence and the nosology
hcaorpp aogtn ilyafciitgn oeeldhoiticbaofruen - of addiction diagnosis. Adistinction is made
srot taht ecudorp e yhttilibarenlu votn oitcidda between ug druse and substance use ders disor
.espaler dna (formerly abuse and dependence). Addiction
27
S U GG ESTED R EADIN G
enorhas and society of centage perge lara fects af - Himmelsbach, C.K., 1943. Can the euphoric, analgetic, and
mous monetary costs. Addiction evolves over physical dependence fects efof ugs drbe separated? . IV
ith Wence eferrto physical dependence. Fed. oc. Pr2,
time, moving om frimpulsivity to compulsivity
201(cid:150)203.
and ultimately being composed of ee thrstages:
ug drin involvement adolescent in Stages 1975. D.B., Kandel,
eoccupation/anticipation, pr binge/intoxication, and use. Science 190, 912(cid:150)914.
withdrawal/negative fect. afMotivational, psycho- subof hypothesis self-medication The 1997. E.J., Khantzian, -
vulnerability and psychological, social dynamic, stance use ders: disora econsideration rand ecent rappli -
. 4, 231(cid:150)244.. Psychiatry. Revcations. Harv
addiction, of etiology the to contribute all factors
., Le Koob, Moal, G.FM., 1997. ug Drabuse: hedonic homeo -
but this book focuses on the oadaptational neur
egulation. Science 278, 52(cid:150)58.static dysr
changes that occur during the addiction cycle. egulation dysraddiction, ug Dr2001. M., Moal, Le ., G.FKoob,
etical theorAuct constris described that derives 24, opsychopharmacology Neurallostasis. and d, ewarrof
subsequent and theories homeostatic early om fr 97(cid:150)129.
2000. H.D., , Kleber., C.PO(cid:146)Brien, D.C., Lewis, ., A.TMcLellan,
ocess opponent theories ovide prto a prbasis for
implications illness: medical onic chra dependence, ug Dr
understanding the obiology neurof addiction.
for eatment, trinsurance, and outcomes evaluation. J.
This ee-stage thrcycle framework is followed Assoc. 284, 1689(cid:150)1695.Am. Med.
in each chapter for each major ug drclass (Psy- ug drof basis neural The 1993. K.C., Berridge, .E., TRobinson,
chostimulants, Opioids, Alcohol, Nicotine, and craving: an incentive-sensitization theory of addiction.
. 18, 247(cid:150)291.Brain Res. Rev
Cannabis).
Solomon, R.L., Corbit, J.D., 1974. An ocess opponent-prthe-
ory of motivation: 1. emporal Tdynamics of fect. afPsy -
Suggested Reading 19(cid:150)145.. 81, 1chol. Rev
Solomon, R.L., 1980. The ocess opponent-pr theory of
Association, 2013. American Diagnostic Psychiatric and Sta - ed acquirmotivation: the costs of e pleasurand the ben -
tistical Manual of Mental ders, Disorfifth ed. American Am. Psychol. 35, 691(cid:150)712.efits of pain.
ashington DC.Psychiatric Publishing, W CYP2A6-mediated ariable V2001. E.M., Sellers, ., R.Fyndale, T
American Psychiatric Association, 1994. Diagnostic and nicotine metabolism alters smoking behavior and risk.
Statistical Manual of Mental ders, Disor fourth ed. ug. Metab. Dispos. 29, 548(cid:150)552.Dr
ashington DCess, W American Psychiatric Pr . i-mapod ni snoitaretlA .0002 ,.W.P ,savilaK ,.J.L ,neruhcsrednaV
, Baumeister., R.FHeatherton, ., .Fice, TTD.M. (Eds.), 1994. d na noitcudni eht ni noissimsnart cigretamatulg dna cigren
Losing ol: ContrHow and Why People Fail at Self- : nw oeliia tvcaf aeioztrii t rlincasornio esifssvoeahrepbxe
ess, San Diego.Academic PrRegulation. 0.21(cid:150)99 ,151 ygolocamrahpohcysP .seiduts lacinilcerp
Colpaert, .C., F1996. System theory of pain and of opiate orld WHealth ganization, Or1992. International Statistical
analgesia: no tolerance to opiates. Pharmacol. . Rev48, Classification of Diseases and Related Health oblems, Pr
355(cid:150)402. ganization, Geneva.orld Health Orevision. W10th r
C H A P T E R
2
Introduction to the
Neuropsychopharmacology
of Drug Addiction
O U T L I N E
The Central Nervous System 30 Norepinephrine 43
Neurons 30 Opioid Peptides 44
Neurotransmission 31 Corticotropin-Releasing Factor 45
Glia 32 Vasopressin 48
Neuropeptide Y 49
Pharmacology for Addiction 33
Nociceptin 50
What is a Drug, and What is Pharmacology? 33
Drug Nomenclature 33 Brain Structures and Functions Relevant
Drug Classification 34 to the Three Stages of the Addiction Cycle 52
Binge/Intoxication Stage – Basal Ganglia 52
Pharmacokinetics 35
Withdrawal/Negative Affect Stage –
Absorption 35
Extended Amygdala 54
Drug Elimination 36
Preoccupation/Anticipation Stage –
Drug Receptors and Signal Transduction 38
Prefrontal Cortex 59
Dose-Response Functions 40
Therapeutic Ratio 41 Neuroadaptational Summary 62
Basic Neurobiology of Addiction 42 Suggested Reading 63
Dopamine 42
“Neuro-,” of or relating to the brain
It tells us how we feel. It allows us to interact
The brain is not simply an amorphous mass of with others and the world. It says when to wake
grayish tissue. It courses with blood and electri- up and when to fall asleep. It helps us put our
cal impulses. It regulates the body’s temperature. shoes on in the morning. It also is susceptible to
Drugs, Addiction, and the Brain
29
http://dx.doi.org/10.1016/B978-0-12-386937-1.00002-7 © 2014 Elsevier Inc. All rights reserved.
30
2. INTRODUCTION TO THE NEUROPSYCHOPHARMACOLOGY OF DRUG ADDICTION
a host of external influences, including drugs. of this book, neurons communicate through cir-
To better understand the subsequent chapters in cuits, and these circuits form the structural bases
this book and to put the medical, biological, and of feelings, thoughts, and behavior, the ultimate
neurobiological mechanisms of drug addiction functional output of the brain.
into context, we must take a step back to define
and explain the common components of the
Neurons
body’s central nervous system, from the macro
(brain regions) to the micro (neurons, neu- Neurons have four major components: (1)
rotransmitters). Armed with this information, cell body, (2) axons, (3) dendrites, and (4) syn-
students will be able to appreciate the in-depth apses (Figure 2.1). The cell body contains the
knowledge that has been gained from extensive nucleus and receives inputs, providing the
scientific research during the past 100 years, machinery for the generation of neurotrans-
with the hope that they, too, will be able to dis- mitters and action potentials. An action poten-
cover greater intricacies to explain why many tial occurs when a neuron’s membrane is
individuals succumb to drug addiction. depolarized beyond its threshold. This depo-
larization is propagated along the axon. The
axon is the “sending” part of the neuron, and
THE CENTRAL NERVOUS SYSTEM
it conducts these action potentials to the syn-
apse to release neurotransmitters. The synapse
The human brain consists of two types of is a specialized space or contact zone between
cells: roughly 100 billion neurons and a greater neurons that allows interneuronal communi-
number of glia. Neurons are highly specialized cation. One or more dendrites comprise the
cells that have an important and unique func- “receiving” part of the neuron, providing a
tional property that is not shared with any other massive receptive area for the neuronal sur-
cells in the body. Neurons communicate with face (Figure 2.2).
each other through both electrical and chemical Neurons act on other neurons to exert three
mechanisms. More importantly for the theme major functions: inhibition, excitation, and
FIGURE 2.1 Anatomy of a neuron.
THE CENTRAL NERvOUs sysTEm 31
neuromodulation. Inhibition means that one Step 2: Neurotransmitter storage.
neuron inhibits another neuron, often through Step 3: Neurotransmitter release from the
the release of an inhibitory neurotransmitter at axon terminal into the synaptic cleft (or from
the synapse. Excitation means that one neuron a secreting dendrite some cases).
activates another neuron through the release Step 4: Neurotransmitter inactivation caused
of an excitatory neurotransmitter at the syn- by removal from the synaptic cleft through
apse. Neuromodulation means that a neuron a reuptake process, or neurotransmitter
influences neurotransmission, often at a long breakdown by enzymes in the synapse or
distance. presynaptic terminal.
Step 5: Activation of the postsynaptic
receptor, triggering a response of the
Neurotransmission postsynaptic cell.
Step 6: Subsequent signal transduction
The communication between neurons can
that responds to neurotransmitter receptor
be distilled into six major steps of neurotrans-
activation.
mission relevant to the neuropharmacology of
addiction (Figure 2.3). Drugs of abuse or drugs that counteract the
Step 1: Neurotransmitter synthesis, effects of drugs of abuse can interact at any of
involving the molecular mechanisms of these steps to dramatically or subtly alter chemi-
peptide precursors and enzymes for further cal transmission to dysregulate or re-regulate,
synthesis or cleavage. respectively, homeostatic function.
FIGURE 2.2 Neurons, synapses, and neurotransmitters. A typical example is shown for the neurotransmitter d opamine.
32
2. INTRODUCTION TO THE NEUROPSYCHOPHARMACOLOGY OF DRUG ADDICTION
FIGURE 2.3 Synaptic neurotransmission. The
figure shows a generalized process of synaptic
transmission. (1) Various components of the neuro-
transmission machinery, such as enzymes, proteins,
mRNA, and so on (depending on the neurotrans-
mitter in question) are transported down the axon
from the cell body. (2) The axonal membrane is
electrically excited. (3) Organelles and enzymes in
the nerve terminal synthesize, store, and release the
neurotransmitter and activate the reuptake process.
(4) Enzymes in the extracellular space and within
the glia catabolize excess neurotransmitters released
from nerve terminals. (5) The postsynaptic receptor
triggers the response of the postsynaptic cell to the
neurotransmitter. (6) Organelles within postsynaptic
cells respond to the receptor trigger. (7) Interactions
between genetic expression and postsynaptic nerve
cells influence cytoplasmic organelles that respond to
neurotransmitter action. (8) Certain steps are modi-
fiable by events that occur at the synaptic contact
zone. (9) The electrical portion of the nerve cell mem-
brane integrates postsynaptic potentials in response
to various neurotransmitters and produce an action
potential. (10) The postsynaptic cell sends an action
potential down its axon. (11) The neurotransmitter is
released. The neurotransmitter that is released from
the nerve terminal can be modulated by autorecep-
tors that respond to the neurotransmitter. [Modified
with permission from Iversen LL, Iversen SD, Bloom FE,
Roth RH. Introduction to Neuropsychopharmacology.
Oxford, New York, 2009, p. 26.]
significantly increase how fast an axon can con-
Glia
duct an action potential. Myelin is a long plasma
In addition to neurons, the central nervous membrane sheet that wraps around each axonal
system contains supporting cells. Supporting segment, leaving bare axons between myelin
cells, generically called glia, can outnumber segments, known as the nodes of Ranvier
neurons by a factor of ten. Historically, glia were (Figure 2.3). Myelin effectively forms insulation
defined as the “nerve glue” that holds neurons that allows the action potential to jump from
together in the central nervous system. How- node to node, known as salutatory conduction.
ever, glia are now known to have key dynamic Astrocytes are star-shaped cells that have
functions in the central nervous system, from processes (branches) and both physical and bio-
myelin synthesis, to synapses, to serving as the chemical support functions in the central ner-
innate brain defensive system against pathology. vous system. They physically isolate neurons
Glia consist of three types of supporting cells: and oligodendrocytes with long processes by
oligodendrocytes, astrocytes, and microglia. making a cover over the nodes of Ranvier and
Oligodendrocytes synthesize myelin and pro- covering the surface of capillaries, forming part
vide an expedient way, via the myelin sheath, to of the blood–brain barrier. Astrocytes play a
PHARmACOLOgy fOR ADDICTION 33
key role in the migration and guidance of neu- chemical reagents or drugs and living organ-
rons during neural circuit development. They isms. A drug is any chemical agent that affects
control the formation, maturation, function, an organism. Obviously, this definition can be
and removal of synapses. They also regulate murky in the domain of drugs of abuse, when
neurotransmission and participate in reuptake one crosses into the realm of natural prepara-
processes, particularly for the excitatory neu- tions that contain psychoactive or psychotropic
rotransmitter glutamate. Astrocytes produce drug entities. Psychotropic can be defined as an
growth factors and signals for activating cyto- effect of a drug on the mind or behavior. For
kines, which can also regulate neurotransmis- example, most drugs of abuse are derived from
sion. They can be activated in a wide range of plant preparations. Many of them are alkaloids,
central nervous system disorders, ranging from such as nicotine in tobacco and caffeine in coffee
neurodegenerative disorders and brain trauma and tea. An alkaloid is an organic compound that
to drug addiction (for further reading, see normally has basic chemical properties and con-
Clarke and Barres, 2013). tains mostly basic nitrogen atoms. So when does
Microglia are immune-like cells in the cen- a compound transition from being a foodstuff to
tral nervous system, comparable to macro- a drug? One metric is when it begins to have an
phages in the immune system. A macrophage is identifiable psychotropic effect.
a large cell that removes waste products, harm- Other terms that are often used in the drug
ful microorganisms, and foreign material from abuse field and should be defined in the
the bloodstream. Immune cells are unlikely to context of this book are toxicology, pharma-
enter the central nervous system because they cotherapeutics, pharmacokinetics, and phar-
cannot cross the blood–brain barrier making macodynamics. Toxicology is the study of the
the brain an immunologically privileged site. harmful effects of drugs. Pharmacotherapeutics
However, microglia may be recruited in the is the study of the diagnostic or therapeutic
brain to serve similar functions. Microglia in effects of drugs. Pharmacokinetics is the study
the central nervous system are activated by of the factors that determine the amount of a
any form of central nervous system injury. given drug at a given site of action. Pharmaco-
They not only remove damaged cells in the dynamics is the study of how a drug produces
brain but also remove synapses that are no lon- its biological effect.
ger functioning. When activated, microglia act
as macrophages and, similarly to astrocytes,
Drug Nomenclature
secrete growth factors and cytokines, both of
which can modulate and regulate neurotrans- Drugs generally have three names: a chemi-
mission (for further reading, see Kettenmann cal name, a nonproprietary (generic) name, and
et al., 2013). a proprietary (trade) name. The chemical name
describes the chemical structure. For example,
7-chloro-2-methylamino-5-phenyl-3-H-1,4-ben-
PHARMACOLOGY FOR zodiazapine-4-oxide is the chemical name for a
ADDICTION benzodiazepine called chlordiazepoxide. Chlor-
diazepoxide is the nonproprietary or generic
name, which is given to a drug when it has
What is a Drug, and What is
been demonstrated to have a therapeutic use.
Pharmacology?
A proprietary or trade name is given by a drug
The following terms need to be defined for company when the drug is patented. Two trade
pharmacological discussions of addiction. Phar- names for chlordiazepoxide are Librium and
macology is the study of the interaction between Mitran.