Anatomical and physiological evidence for D-1 and D-2 dopamine receptor colocalization in neostriatal neurons.. Altered GABAergic neurotransmission in mice lacking dopamine D2 recep-tors
Trang 1NOS-containing neurons, by modulating the activity of
medium spiny neurons in response to cortical inputs,
also play an important role in the expression of
synap-tic plassynap-ticity at corsynap-ticostriatal synapses (Centonze
et al., 1999, 2003c)
Therefore, the striatum, by processing the
informa-tion flow from various inputs and sending output to
targets that generate behaviors (Grace, 2000), plays a
key role in adaptive plasticity in corticobasal ganglia
as well as in pathological responses in PD
Acknowledgments
The authors would like to thank Laurent Gregoire for
helping in the management of the references in the text
and Gilles Chabot for preparing the figures This work
is supported by grants from the Canadian Institutes of
Health Research (CIHR) to TDP, PJB and CR PS
holds a fellowship from CIHR-RX&D
References
Aizman O, Brismar H, Uhlen P et al (2000) Anatomical
and physiological evidence for D-1 and D-2 dopamine
receptor colocalization in neostriatal neurons Nat
Neu-rosci 3: 226–230
Akil H, Owens C, Gutstein H et al (1998) Endogenous
opioids: overview and current issues Drug Alcohol
Depend 51: 127–140
Alberch J, Perez-Navarro E, Canals JM (2002)
Neuropro-tection by neurotrophins and GDNF family members in
the excitotoxic model of Huntington’s disease Brain
Res Bull 57: 817–822
Alexander GE, Crutcher MD (1990) Functional
architec-ture of basal ganglia circuits—neural substrates of
paral-lel processing Trends Neurosci 13: 266–271
Alexi T, Hughes PE, Roon-Mom WM et al (1999) The
IGF-I amino-terminal tripeptide
glycine-proline-gluta-mate (GPE) is neuroprotective to striatum in the
quinoli-nic acid lesion animal model of Huntington’s disease
Exp Neurol 159: 84–97
Alger BE (2002) Retrograde signaling in the regulation of
synaptic transmission: focus on endocannabinoids Prog
Neurobiol 68: 247–286
Aliaga E, Carcamo C, Abarca J et al (2000) Transient
increase of brain derived neurotrophic factor mRNA
expression in substantia nigra reticulata after partial
lesion of the nigrostriatal dopaminergic pathway Brain
Res Mol Brain Res 79: 150–155
Allen JM, Cross AJ, Crow TJ et al (1985) Dissociation of
neuropeptide Y and somatostatin in Parkinson’s disease
Brain Res 337: 197–200
An JJ, Bae MH, Cho SR et al (2004) Altered GABAergic
neurotransmission in mice lacking dopamine D2
recep-tors Mol Cell Neurosci 25: 732–741
Angulo JA, McEwen BS (1994) Molecular aspects of neu-ropeptide regulation and function in the corpus striatum and nucleus accumbens Brain Res Rev 19: 1–28 Arai H, Sirinathsinghji DJ, Emson PC (1987) Depletion in substance P- and neurokinin A-like immunoreactivity in substantia nigra after ibotenate-induced lesions of stria-tum Neurosci Res 5: 167–171
Arenas E, Alberch J, Pereznavarro E et al (1991) Neuro-kinin receptors differentially mediate endogenous acetyl-choline-release evoked by tachykinins in the neostriatum
J Neurosci 11: 2332–2338
Arenas E, Perez-Navarro E, Alberch J et al (1993) Selec-tive resistance of tachykinin-responsive cholinergic neu-rons in the quinolinic acid lesioned neostriatum Brain Res 603: 317–320
Arluison M, De La Manche I (1980) High-resolution radio-autographic study of the serotonin innervation of the rat corpus striatum after intraventricular administration of [3H]5-hydroxytryptamine Neuroscience 5: 229–240 Augood SJ, Herbison AE, Emson PC (1995) Localization
of GAT-1 GABA transporter mRNA in rat striatum: cel-lular coexpression with GAD67 mRNA, GAD67 immu-noreactivity, and parvalbumin mRNA J Neurosci 15: 865–874
Augood SJ, Waldvogel HJ, Munkle MC et al (1999) Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human sub-thalamic nucleus Neuroscience 88: 521–534
Azzi M, Gully D, Heaulme M et al (1994) Neurotensin receptor interaction with dopaminergic systems in the guinea-pig brain shown by neurotensin receptor antago-nists Eur J Pharmacol 255: 167–174
Bai L, Xu H, Collins JF et al (2001) Molecular and func-tional analysis of a novel neuronal vesicular glutamate transporter J Biol Chem 276: 36764–36769
Baik JH, Picetti R, Saiardi A et al (1995) Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors Nature 377: 424–428
Balasubramaniam A (2003) Neuropeptide Y (NPY) family
of hormones: progress in the development of receptor selective agonists and antagonists Curr Pharm Des 9: 1165–1175
Bamford NS, Zhang H, Schmitz Y et al (2004) Heterosy-naptic dopamine neurotransmission selects sets of corti-costriatal terminals Neuron 42: 653–663
Barker R (1986) Substance P and Parkinson’s disease: a causal relationship? J Theor Biol 120: 353–362 Barker R (1991) Substance P and neurodegenerative disor-ders A speculative review Neuropeptides 20: 73–78 Barker R (1996) Tachykinins, neurotrophism and neurodegen-erative diseases: a critical review on the possible role of tachykinins in the aetiology of CNS diseases Rev Neurosci 7: 187–214
Barker R, Larner A (1992) Substance P and multiple sclerosis Med Hypotheses 37: 40–43
Barker R, Dunnett S, Fawcett J (1993) A selective tachykinin receptor agonist promotes differentiation but not survival of rat chromaffin cells in vitro Exp Brain Res 92: 467–472
Trang 2NOS-containing neurons, by modulating the activity of
medium spiny neurons in response to cortical inputs,
also play an important role in the expression of
synap-tic plassynap-ticity at corsynap-ticostriatal synapses (Centonze
et al., 1999, 2003c)
Therefore, the striatum, by processing the
informa-tion flow from various inputs and sending output to
targets that generate behaviors (Grace, 2000), plays a
key role in adaptive plasticity in corticobasal ganglia
as well as in pathological responses in PD
Acknowledgments
The authors would like to thank Laurent Gregoire for
helping in the management of the references in the text
and Gilles Chabot for preparing the figures This work
is supported by grants from the Canadian Institutes of
Health Research (CIHR) to TDP, PJB and CR PS
holds a fellowship from CIHR-RX&D
References
Aizman O, Brismar H, Uhlen P et al (2000) Anatomical
and physiological evidence for D-1 and D-2 dopamine
receptor colocalization in neostriatal neurons Nat
Neu-rosci 3: 226–230
Akil H, Owens C, Gutstein H et al (1998) Endogenous
opioids: overview and current issues Drug Alcohol
Depend 51: 127–140
Alberch J, Perez-Navarro E, Canals JM (2002)
Neuropro-tection by neurotrophins and GDNF family members in
the excitotoxic model of Huntington’s disease Brain
Res Bull 57: 817–822
Alexander GE, Crutcher MD (1990) Functional
architec-ture of basal ganglia circuits—neural substrates of
paral-lel processing Trends Neurosci 13: 266–271
Alexi T, Hughes PE, Roon-Mom WM et al (1999) The
IGF-I amino-terminal tripeptide
glycine-proline-gluta-mate (GPE) is neuroprotective to striatum in the
quinoli-nic acid lesion animal model of Huntington’s disease
Exp Neurol 159: 84–97
Alger BE (2002) Retrograde signaling in the regulation of
synaptic transmission: focus on endocannabinoids Prog
Neurobiol 68: 247–286
Aliaga E, Carcamo C, Abarca J et al (2000) Transient
increase of brain derived neurotrophic factor mRNA
expression in substantia nigra reticulata after partial
lesion of the nigrostriatal dopaminergic pathway Brain
Res Mol Brain Res 79: 150–155
Allen JM, Cross AJ, Crow TJ et al (1985) Dissociation of
neuropeptide Y and somatostatin in Parkinson’s disease
Brain Res 337: 197–200
An JJ, Bae MH, Cho SR et al (2004) Altered GABAergic
neurotransmission in mice lacking dopamine D2
recep-tors Mol Cell Neurosci 25: 732–741
Angulo JA, McEwen BS (1994) Molecular aspects of neu-ropeptide regulation and function in the corpus striatum and nucleus accumbens Brain Res Rev 19: 1–28 Arai H, Sirinathsinghji DJ, Emson PC (1987) Depletion in substance P- and neurokinin A-like immunoreactivity in substantia nigra after ibotenate-induced lesions of stria-tum Neurosci Res 5: 167–171
Arenas E, Alberch J, Pereznavarro E et al (1991) Neuro-kinin receptors differentially mediate endogenous acetyl-choline-release evoked by tachykinins in the neostriatum
J Neurosci 11: 2332–2338
Arenas E, Perez-Navarro E, Alberch J et al (1993) Selec-tive resistance of tachykinin-responsive cholinergic neu-rons in the quinolinic acid lesioned neostriatum Brain Res 603: 317–320
Arluison M, De La Manche I (1980) High-resolution radio-autographic study of the serotonin innervation of the rat corpus striatum after intraventricular administration of [3H]5-hydroxytryptamine Neuroscience 5: 229–240 Augood SJ, Herbison AE, Emson PC (1995) Localization
of GAT-1 GABA transporter mRNA in rat striatum: cel-lular coexpression with GAD67 mRNA, GAD67 immu-noreactivity, and parvalbumin mRNA J Neurosci 15: 865–874
Augood SJ, Waldvogel HJ, Munkle MC et al (1999) Localization of calcium-binding proteins and GABA transporter (GAT-1) messenger RNA in the human sub-thalamic nucleus Neuroscience 88: 521–534
Azzi M, Gully D, Heaulme M et al (1994) Neurotensin receptor interaction with dopaminergic systems in the guinea-pig brain shown by neurotensin receptor antago-nists Eur J Pharmacol 255: 167–174
Bai L, Xu H, Collins JF et al (2001) Molecular and func-tional analysis of a novel neuronal vesicular glutamate transporter J Biol Chem 276: 36764–36769
Baik JH, Picetti R, Saiardi A et al (1995) Parkinsonian-like locomotor impairment in mice lacking dopamine D2 receptors Nature 377: 424–428
Balasubramaniam A (2003) Neuropeptide Y (NPY) family
of hormones: progress in the development of receptor selective agonists and antagonists Curr Pharm Des 9: 1165–1175
Bamford NS, Zhang H, Schmitz Y et al (2004) Heterosy-naptic dopamine neurotransmission selects sets of corti-costriatal terminals Neuron 42: 653–663
Barker R (1986) Substance P and Parkinson’s disease: a causal relationship? J Theor Biol 120: 353–362 Barker R (1991) Substance P and neurodegenerative disor-ders A speculative review Neuropeptides 20: 73–78 Barker R (1996) Tachykinins, neurotrophism and neurodegen-erative diseases: a critical review on the possible role of tachykinins in the aetiology of CNS diseases Rev Neurosci 7: 187–214
Barker R, Larner A (1992) Substance P and multiple sclerosis Med Hypotheses 37: 40–43
Barker R, Dunnett S, Fawcett J (1993) A selective tachykinin receptor agonist promotes differentiation but not survival of rat chromaffin cells in vitro Exp Brain Res 92: 467–472
Trang 3Chapter 3
Neurophysiology of basal ganglia diseases
Department of Neurosciences and Neuromed Institute, Universita` La Sapienza, Rome, Italy
The a natomical s tructures of the basal ganglia are
connected to each other by a ne twork of i nterconnections
and t he functional organization is based on the
connec-ti ons wi th t h al am us and c orconnec-ti cal terri tori es ( Albin et al.,
1989; Alexander a nd Crutcher, 1990; Mink, 1996; Parent
and Hazrati, 1995) Movement disorders (parkinsonisms,
dystonias and choreas) can be considered the r esult of
alterat ions i n the c ort ico-stria to-thalamo-cortical circui t
(DeLong, 1990 ) Func tional connections of the b asal
gang lia with other structures o f the ne rvous s ys tem
(brain-stem and spina l cord) are a lso r elevant in the pa
thophy-siolog y of mov ement disorders A significant part o f o ur
speculations on the p hysiological role of the basal ganglia
in huma n b eings d erives from studie s cor rela ting n
euro-physiological deficits with specific lesions of the b asal
gang lia structures (Bera rde lli & C ur ra` , 2002)
In this chapter we will review the neuro physiolo
gi-cal findings descr ibed in patient s with Parki nson’s
disease (PD), dystonia and Hunti ngton ’s disease (HD)
3.1 Parkinson’s disease
In recent years, considerable advances have taken place
in the understanding of the pathophysiology of PD
In experiments conducted on animals rendered
parkinso-nian through the administration of
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and more recently
in parkinsonian patients undergoing surgery for deep
brain stimulation, the activity from specific neuron
popu-lations can be recorded through electrodes implanted
directly into the basal ganglia nuclei After nigral
degen-eration there is an altered neuronal output from the
subthalamic nucleus and globus pallidus (Hutchison
et al., 1997) This abnormal neuronal activity brings
about a functional change in the motor circuits that link
the basal ganglia to the motor cortical area Striatal
dopa-mine depletion in PD reduces the activity of thalamic nuclei projecting to the frontal lobe, leading to cortical deafferentation Such alterations are held responsible for the motor disturbances typical of PD (Berardelli
et al., 2001)
Move ment slowne ss (bradykin esia), toge ther with muscular rig idity and tremors, are amo ng the principal symptoms of PD Pathophysi ologica l stud ies have demonstrat ed that brady kinesia is in part cause d
by defective preparati on of volun tary move ment The usual way of inve stigatin g moveme nt prepa ration
of a volun tary move ment is to study the reaction time (RT) The RT ref ers to the interv al elapsing betwee n the stim ulus to move and moveme nt initiatio n The RT include s stim ulus processi ng, the use of work-ing memory for the retri eval of stimulus map pwork-ings and the gener ation o f predict ions and decisi on-maki ng Several studies have provided evidence that parkinso-nian patients have an increased RT (Evarts et al., 1981; Jahanshahi et al., 1992), particularly for the more difficult tasks Preparation of movements can also be studied by recording the slow-rising negative electro-encephalogram (EEG) potentials generated before the onset of a voluntary movement (premotor potentials) The premotor potential begins about 2 s before the onset of a voluntary movement and is thought to be generated in the primary and non-primary cortical motor a reas In patients with PD, t he pr emo t or po ten tials have reduced amplitude, probably owing to reduced activation of cortical motor areas, particularly of supple-mentary motor areas (Dick et al., 1989; Jahanshahi
et al., 1995)
Besides causing defective movement preparation,
PD also leads to alterations in movement execution Studies on electromyogram (EMG) and kinematic activity show that parkinsonian patients have difficulty
*Correspondence to: Professor Alfredo Berardelli, Department of Neurological Sciences and Neuromed Institute, Universita`
La Sapienza, Viale dell’ Universita` , 30, 00185 Roma, Italy E-mail: alfredo.berardelli@uniroma1.it, Tel: þ 39-06-4991-4700, Fax: 39-06-4991-4700
Parkinson’s disease and related disorders, Part I
W.C Koller, E Melamed, Editors
# 2007 Elsevier B.V All rights reserved
Trang 4Chapter 4
Dopamine receptor pharmacology RICHARD B MAILMAN 1,2* AND XUEMEI HUANG 2
1
Departments of Psychiatry, 1Pharmacology, 2 Neurology and Medicinal Chemistry,
University of North Carolina School of Medicine, Chapel Hill, NC, USA
4.1 Dopamine receptor biology
4.1.1 Bac kground
Despite a h alf-centu ry of rese arch since the first drugs
that bind to dopamin e rece ptors (e.g chlorpr omazine)
were used in clinical med icine, the under lying
mechani sms are still poorl y under stood The biochem
-ical assays developed by Arvid Ca rlsson and othe rs
( Carlsson, 195 9), as well as histologi cal tec hniques
( Hillarp et al., 1966 ), paved the way for understa nding
dopam ine functi on in the brai n These stud ies showed
there were three major dopamin e path ways, including
the nigrost riatal (from cells in the A9 region) , the
mesolim bic-cor tical (from cells in the A10 o r v entral
tegmen tum) and the tuberoi nfundibular (hypot
ha-lami c) system ( Ungerstedt , 19 71a) This early
aware-ness of the chemoar chitec ture of dopam ine systems
opened the doors to an u nderstandin g of the functi onal
role of dopam ine in comple x phenom ena med iated by
the brain areas modulated by do pamine Indee d, soon
after the disco very of chlorpr omazin e, it was demon
-strat ed that decrease s in acute agitati on, hallucinat ions
and othe r psycho tic sign s and sym ptoms were fre
-quent ly accompa nied by disturb ing and unwa nted
neuro logical side-effe cts (drug-in duced parkinso nism,
akathesi a and acute dyst onic reac tions), now known
as extrapyr amidal side -effects This similarity of
acute drug- induced neurologica l side-effe cts and
Parkinson ’s disease ( Ehringer and Hor nykiewicz ,
1960; Hornyki ewicz, 1971 ) sugges ted a mechanist ic
relat ionship ( Carl sson and Lindqv ist, 1963 ) that
marked the beginning of the field of dopamine receptor
pharmacology
Al though dopam ine recepto rs had been hypothe-sized for nearly a decad e, the first dir ect bioch emical mechanism linked to them cam e from the labo ratory
of Paul Greenga rd, who demonst rated that dopamin e could dose-depe ndent ly stimula te the synt hesis of the second-m essenger cyclic adenos ine monoph osphate (cAMP: Kebabi an et al., 1972 ) in a fashion that was antagonized by antipsy chotic d rugs ( Clement-Cor mier
et al., 1974 ) Th e fact that bo th phenothi azine and thioxanthi ne antipsy chotics com petitively inhibited the dopamin e-stimulat ed act ivity of adenyl ate cyclase
in p roportion to their clini cal po tency led to the notion that thi s was the major funct ional mec hanism o f dopa-mine in the cent ral nervo us system ( Clement-Cor mier
et al., 1974 ; Iversen, 1975 )
However, with the introduction of new antipsychotics
in still newer s tructural c lasses (e.g b utyrophenones and benzamides), marked discrepancies b ecame apparent
Fo r e xam ple, m a ny of t he se new b ehaviorally potent antipsychotics h ad littl e potency in inhibiting dopa-mine -stimulated a de nylate cyclas e ( Trabucchi et al.,
19 75 ) T h is d iscre pa nc y led to the idea tha t two ty pe s
of dopamine receptors existed One class was the o riginal ade nylate c ycla se -linked r ece ptor f irst repor ted b y G ree n-gar d’s gr ou p ( Keba bia n e t al , 19 72 ), that bound w ith highaffinity thioxanthines a nd ph en oth iaz ine antip sy -chotics, but not drugs of the butyrophenone or benza-mide classes (Garau et al., 1978) The other class of dopamine receptor was not linked to stimulation of ade-nylate cyclase, but bound all of these drugs in proportion
to their clinical potency (Burt et al., 1976; Creese et al., 1976; Seeman et al., 1976) This differentiation, coupled with other information about the localization and func-tion of dopamine receptors, led to the specific hypothesis
*Correspondence to: Dr Richard B Mailman, CB # 7160, University of North Carolina School of Medicine, Chapel Hill, NC 27599-7160, USA E-mail: richard_mailman@med.unc.edu, Tel: þ 1-919-966-3205, Fax: þ 1-966-1844
Parkinson’s disease and related disorders, Part I
W.C Koller, E Melamed, Editors
# 2007 Elsevier B.V All rights reserved
Trang 5Section 2 General aspects of Parkinson’s disease