Subject Index

A-84543 420(fig.),441 - regulation 182-184 A-85380 420(fig.),441 acute sensitivity, animal studies A-98593 441 566-572 ABT-089 326-327, 420(fig.), 441 - acute sensitivity, genetics 566-569 ABT-418 231, 326-327, 420(fig.), 800, 802 - tolerance development, genetic ABT-594 420(fig.), 441, 800 influences 569-571 1-acetyl-4-methyl- 609 addiction 605, 650-654 13, 420(fig.), 436, 764-765 Addiction Research Center Inventory - release, auto-facilitatory effect 7 (ARCI) 621 - structure 81 (fig.) adenosine triphosphate nicotinic -inducing activity receptor, presynaptic 200 (ARIA) protein 96 adrenalectomy 429 acetylcholine receptors (AChRs) binding site 278-282 - central nervous system 165-176 - ACh binding, structural determinants - features of sequence 85(fig.) 278-279 - nicotinic receptors - nAChR pharmacological profile, -- brain 301-303 allosteric modulation 279-282 -- central nervous system, distribution alcoholism 754 779 allosteric effector 277 -- characterization 82 - voltage-dependent modulation -- decline with ageing 755(table) 292(fig.) -- distribution with respect to allosteric model 275-276 neurons 20-25 allosteric modulators, drug candidates -- invertebrates 513-514 487--490 -- isolation 82 allostericaly potentiating ligands 484 -- modulatory control by allostericaly d2 gene acting ligands 483--487 - avian K2 regulatory region 60 -- monitoring, experimental - silencer region 60-61 requirements 338-339 a-3 gene 46--47 -- neuronal, structures 101-146 a-7 gene 45--46 -- presynaptic 7-8,195-196 - bovine a-7 promoter 61-62 --- ganglia 257-258 - chicken a-7 promoter 61 --- pharmacology 195-200 a-7 gene, seizure disorders 576 -- skeletal muscle a-7 receptor, properties 323-325 --- biophysical properties 88-89 a- (K-bgt) 4,7,89,383, --- functional aspects 81-82 455 --- structure 83-88 - neuromuscular transmission, inhibition -- subtypes 680-681 80 -- upregulation 665-667 a-cobra toxin 89 - neuronal surface 176-182 a- AulE 469 - regional distribution, peripheral a-conotoxin Epl 469--470 nervous system 164-165 a-conotoxin Iml 455, 467--468 814 Subject Index a-conotoxin MI 470 -- transgenic analysis 63-64 a-conotoxin MIl 465-467 - neuron restrictive silencer element 64 a-conotoxin PnIAIPnIB and analogues - silencing elements, role of 44-45 469 fJ-4 gene 46-47 a- 89 fJ-endorphine concentration 706-707, a-neurotoxin family 89-91 781 Alzheimer's disease 487,755-757, bHLH transcription factors, f33 758-760, 780(table) regulation in retina 47-49 - K-7 selective 133 bilayer reconstructed nAChRs 359- - brain nAChRs 325-326 375 - cognitive dysfunction, nicotine - chick a-6 subtype 370-372 treatment 593-594 - chick a-7, a-8 and a-7-a-8 subtypes - nicotine binding sites, affinity 144 368-370 - nicotine, treatment 594,788-793 - functional channel reconstruction -- amyloid deposition 490 362-363 -- skin patches 588 - insect a-bgt receptors 368 - PET studies of nAChRs 549-554 - lipid bilayers, formation 360 - trans-meta-nicotine 439 - muscle-type receptor 363-367 amacrine cells, retina 17 -- a-2/3 r 8 nAChRs channels Amanita muscaria 79 364-365 amino acid transmitter 708 -- a-2/3 r 8 nAChRs in oocytes 366 amobarbital 428 -- a-2/3 r 8 nAChRs reconstructed in 533,609,611 lipid bilayer 365-366 amyloid and neuronal nAChRs 233 - nAChRs subtypes for reconstruction, anabaseine 307, 420(fig.), 439, 609, 801 purification 360-362 analgesia 799-800 - neuronal type receptor 367-372 anatoxin-a 440 brain, age-related degenerative diseases anotoxin 609 754-761 anxiety 802-803 brain nAChRs 272,301-303 anxiogenic drug stimulus 679 - high affinity receptors 315 apolipoprotein E, neuronal nAChRs -low affinity receptors 315 234 brain slice recording 301 APV 349 brainstem 16 arachidonic acid site 430 bromo acetylcholine 84-85 (figs ), 86 atherosclerosis 763 atropine 349,455,484 609 attention deficit hyperactivity disorder calbindin 134 587,798-799 calcitonin gene-related peptide 96,328, - nicotine patch administration 594 430 autocrine growth factor 134 calcium influx entry 5 autoreceptors 23-24, 193 calcium, neuronal nAChRs 305-306 - subunit composition 24 calnexin 93 Cam kinase II 204-205 609 420(fig.),436 basal telencephalic system 13-15,18- monotherapy 290 19(tables) carbamylcholine 316 basic fibroblast growth factor 228 carotid body, chemosensory cells 164 benzodiazepines 609 CAT 43 benzoquinonium 427 caudate putamen 15 benzylisoquinoline family 80 central nervous system (CNS) /34, a3, as gene cluster 64-65 - AChRs, distribution on the neural fJ-2 gene surface 180-181 - fJ-2 promoter - AChRs, regional distribution 165-176 -- mouse 63 -- chicken brain, mapping 176 Subject Index 815

-- mammals, species differences cyttsme 422(fig.), 435, 609 175-176 cytoprotection 800-802 -- mapping studies 166,173-175 - neuronal nAChRs, functions served D-erythro-sphingosine 204 315-316 d-tubocurarine 41,80-81,316, 422(fig.), CGS-10746B 613-614 456-458 channel domain, schematic - competitive neuromuscular blockade representation 283(fig.) 82 chick ciliary ganglion 255(fig.),257 DBO-083 420(fig.) "chipping" 606 4,422(fig.) 312, 422(fig.), 674 dementia with Lewy Bodies 232, 757- chlorpromazine 291, 422(fig.), 427 758 436 dependence, definition 604 cholinergic agonists 609 depression 754, 780(table), 802-803 cholinergic channel dexamethasone 429 - modulators 441-442 dihydropyridine, binding site 429-430 -- orders or potency and efficacy discriminative stimulus effects, nicotine 433(table) see nicotine dependence cholinergic neurons 422(fig.),593 - neural tissue 13-20 DMXB 439, 801 - vertebrate species vs. CNS, comparison donepezil 553 between 18-19(tables) 317,607,681-704 cholinergic systems - desensitization 691-692 - main, mammalian brain 14(fig.) - discriminative stimulus effects of - wiring vs. volume transmission 24-25 nicotine, role of 611-614 inhibitors 553-554 - neurons ciliary neuron, synaptic specialization -- glutamate, role of 689-690 associated with an E15 255(fig.) -- nAChRs (a-7-containing), role of ciliary neurotrophic factor 216 689-690 Cis-acting regulatory elements, -- nAChRs, expression of 681 identification 43-49 -- nAChRs (somato-dendritic), closed-channel trapping 4 inactivation 692-693 CNQX 349 -- nicotine, electrophysiological effects 533-534,611-612 688-689 cochlear ganglia 17 - nicotine-self administration, role of cognitive function 782-783,787-788 636-639 - behavioural effects 782-783 - nicotinic receptors, presynaptic - role of nAChRs 587-595 196-197 -- animals, laboratory 588-589 - release, nAChRs activation 21 -- humans, effects in 587-588 - studies -- neural basis, cognition 589-592 -- ex vivo 684-688 -- neurotransmitter interactions -- in vitro 682 592-593 -- in vivo 684-688 conditioned taste aversion (CTA) - transmission paradigm 619-620 -- adaptive changes after nicotine conotoxins 383 exposure 690-691 conus venom peptides 464-470 -- sensitization to nicotine 698 781 -- tolerance and dependence 693- craving 677 698 critical flicker fusion 794 dorsal root ganglia (DRG) 17 Crohn's disease 765 Down syndrome, nicotinic binding 232 - smoking 145 drug abuse 606 455 duhydro-f3-erythroidine 422(fig.), CYP-2A6 781 456(fig.),458-459 816 Subject Index epibaditine 231,303,328, 420(fig.), 440, - release, nAChRs activation 21 763, 799-800 growth factors 551-552 Epiboxidine 420(fig.) GTS-21 326-327, 420(fig.), 439, 800 epilepsy 753-754, 780(table), 803 - autosomal dominant nocturnal frontal habenulo-interpeduncular tract 14(fig.), lobe epilepsy (ADNFLE) 144,289- 15, 18-19(table) 290,575-576,803 habituation 605 erabutoxin-a 89 594,707,785-786,797 ethanol 533 head injury 754 excitatory postsynaptic potential 81-82 heterologous expression 514-515 exocytosis 203 heteroreceptors 21-23, 193-194 - subunit composition 22-23 facilitation 258 4,7,312-314,383, fasciculus retroflexus of Meynert 6-7 422(fig.), 620, 650, 754 FK1 427 Hill coefficient 83 FR-lO 645 hippocampal neurons FRAs 708-710 - conventional slices, nicotinic receptors Fyn 205 343-345 - cultured, nicotinic receptors 339-343 GABAergic and glutaminergic synaptic hippocampus transmission, hippocampus 345-348 - CAl field, synaptic transmission by a-7 galanthamine 427 subunit 348-350 y.aminobutyric acid (GABA) 21-22 histrionicotoxin 427,435 - nicotinic receptors, presynaptic 5-HT3 receptor antagonists 687 198-199 human a-3 promoter 66-68 ganglia, autonomic Huntington's disease 786 - AChRs distribution 164--165 hydrocortisone 429 - nAChRs subtypes 247 hydroxycortisone 291 ganglia, nicotinic receptors 5-hydroxytryptamine nicotinic receptors, - composition 248-250 presynaptic 198 - electrophysiological features 249- hypertension 763-764 250 hypothalamus, cholinergic neurons, - immunological identification 248- distribution invertebrate species 18- 249 19(tables) - presynaptic 257-258 ganglion blocking agents 312-314,764 688 ganglionic nicotinic receptors imidacloprid, structure 512(fig.),513 - regulation 258-262 induce fit model 275 -- cell-cell interactions, receptor inflammatory bowel disease 765 regulation 258-259 inhibitory postsynaptic potential 6 -- developmental regulation 259-260 inter alia 6 -- molecular controls 260-262 internodal cells Chara corallina alga 34 ganglionic transmission, nAChRs irreversible pharmacological blockade 247-262 6 GBR-12909 612-613 islands of Calleja 15 gene(s) expression 708-710 isoarecoline 609-610 - changes with development 308-310 428 genistein 205 420(fig.) GFP 43 glutamate k-bungarotoxin 4,250 - antagonists 7 keratinocytes 764-765 - nicotinic receptors, presynaptic 199- knockout mice, as models 525-534 200 - behavioural analysis 533-534 - NMDA-type receptors 395-396 - muscle nAChRs subunits 526-530 Subject Index 817

- neuronal nAChRs, pharmacology myasthenic syndromes 530-533 - congenital -- AChRs mutations 124 LacZ 43 -- receptor mutations 91-93 latent inhibition 660-661 leukaemia inhibiting factor 216 Naja mossambica mossambica lithium 620 neurotoxin (Nmm I) 89-91 609, 802 Naja toxin 4 locomotion, nicotine effects on 656-660 naloxone 673,706-707 Lophogorgia toxin 80 native nicotinic receptors lophotoxin 435, 456(fig.), 460-461 - chick ciliary ganglion 385-388 - structure 81(fig.) - embryonic chick sympathetic lymphocytes 765-766 ganglion neurons, antisense methods 392-394 M-maleimidobenzyl trimethylammonium - intracardiac ganglia 388-389 84-85(figs),86 - rat superior cervical ganglion- 6-7,205,312-314,383, macroscopic currents 389-390 422(fig.), 593, 610-611, 616, 619-620, - single channel studies 390-392 630,673,794 nerve growth factor 261 medial habenula 320 neuregulin variant protein 261 medullary reticular formation, neuroleptic agents 609,751 cholinergic neurons, distribution in neurological diseases, channel mutations vertebrate species 18-19( tables) 289-290 medullary tegmentum 14(fig.),I6-17 neuromuscular junction, synaptic delay memory function, NMDA glutamate times (studies) 79 receptor 593 neuron restrictive silencer element 44, mesopontine tegmental system 14(fig.), 59 16 neuronal bungarotoxin 250-251 - cholinergic neurons, distribution in neuronal nicotinic acetylcholine vertebrate species 18-19( tables) receptors (nAChRs) methyllycaconitidine 383, 422(fig.), 435, - activators 420(fig.) 456(fig.), 459, 512 - biophysical properties to human methylpiperidine 436 diseases 271 miniature endplate potentials 81 - cell loss 294-295 MK-80l 427 - central nervous system development 673 217-224 motor endplate potential 81 - developing therapeutics 325-328 muscarine 79,419-420 - distribution 163-185 muscarinic antagonists 609 - during ageing muscarinic cholinergic response, -- normal 229-231 regulation 221-222 -- normal and pathological 232-235 muscle AChRs 394-395 -- pathological 231-232 -longitudinal view 84-85(figs) - expression in, mammalian muscle and - subunits 102 tegumental cells 478-481 -- cation-specific channels 123 - gene structure and transcriptional -- central cation channel, organization regulation 33-49,101-146 110 - heteromeric 134-137 -- cytoplasmic domain 123-124 -- central channel, subunit organization -- extracellular domain, ACh binding 139 sites 110-112 -- neuronal diseases-involvement -- extracellular domain and myastenia 144-146 gravis, immunogenic region -- special properties 140-144 112-123 -- subunits, structures 137-139 -- structures 103-109 - homomeric 124-125 818 Subject Index

-- central channel, subunit organization - pharmacokinetics 781 128-131 - pyridine ring modified analogs 437 -- neuronal diseases, involvement - ring modified analogs 133-134 437 -- special properties 131-133 - related behaviour, genetic regulation -- structures 127 563-579 -- subunits 125-127 - replacement, smoking cessation 303 - human, single channel recordings - self-administration 625-654 285-286 -- animals, model of human nicotine - inhibitors 422(fig.) addiction 650-654 - native and recombinant, comparison -- animals, nicotine antagonists 379-407 632-633 - nicotinoceptive cells, development - - craving, reinstatement 639-640 224-228 -- dopamine, role of 636--639 - peripheral nervous system, -- extinction 633-635 development 213-216 -- human studies 639 - pharmacology 306-308 -- intravenous 626-632, 640-643, 645 -- perspectives on the future 442 -- oral 643-644 -- properties 431-434 -- pharmacokinetic factors 625-626 - potency ratios 397-398 - skin patches - receptors with more than two types of -- Alzheimer's disease 588 subunits 401-403 -- Tourette's syndrome 144-145 - schematic organization 273(fig.) - spray 615,621,646-648 -- allosteric model 275-277 - action 3 -- functional domains 277-278 - withdrawal 672-680 -- recording and reconstruction 274- -- animal studies 673-676 275 -- humans 676-678 - single channel properties 398-401 nicotine abstinence syndrome 673 - subunit genes, transcription regulation nicotine dependence 57-73 - addiction 603-606 neuropeptide FF 673 - behavioural stimulus effects 606-656 neurotoxin-l 79 -- aversive properties 619-622 neurotransmission -- conditioned place-preference 654- - ionotropic receptors 271 656 - metabotropic receptors 271 -- discriminative stimulus effects 607- neusurugatoxin 435, 456(fig.), 460 618 NF-l 47 -- motivational stimulus effects 618- Nicotina tabacum 79 619 nicotine 79,419-420, 422(fig.), 525, 533 -- operant behaviours, effects of - adaptation 661-680 nicotine 622-625 -- cellular basis 664-665 -- self-administration 625-654 - cerebral metabolic activity 685-686 - definition 603-606 - conformationally restricted analogs nicotinic acetylcholine receptors 438-439 (nAChRs) - effects on: - activation and inhibition 434-441 -- endothelial cells 762-763 - agonists and antagonists 419-442 -- intestinal epithelium 765 - a subunit, ectopically expressed - -lung cells 762 N-terminal extracellular domain -- vascular smooth muscle 762-763 481-483 - intracranial self-stimulation 623-624 - central nervous system 5-7 - memory improvement 232-233 - dopaminergic, glutaminergic, - neurotoxic effects 235 cholinergic inputs, striatum 194(fig.) -- mediated by a-7 AChRs 133-134 - expression - pharmacodynamics 781 -- regulation 95-96 Subject Index 819

-- role in innervation and target tissues - subtypes identification, radioligands 41-42 used 424 - function, inhibition, ligand-binding - subunits, molecular biology 423-424 sites 427-430 - type a4, seizure disorders 575-576 - ganglionic transmission 247-262 nicotinic agonists - genes, model for neuron-specific gene - Alzheimer's disease, studies 791-793 transcription 43 - effect on potential applications in - historical perspective 421-423 human CNS disorders 780(table) - insects 497-515 - neuroprotective capacity 760 -- a-bgt-binding receptor complexes, - symptomatic benefits 760-761 purification 506-507 nicotinic antagonists -- cloned subunits with a-bgt, - Alzheimer's disease, studies 790-791 correlation 507-508 - nicotine self-administration in animals -- cloned subunits, expression in 632 heterologous system 508 nicotinic cholinergic neurotransmission, -- molecular cloning 498-504 drug action 489(fig.) -- neuronal receptors, nicotinic modulation of transmitter electrophysiological characterization release, molecular/cellular mechanisms 511-512 200-205 -- nicotinic receptors, targets for nicotinic receptors insecticides 512-513 nimodipine 422(fig.) -- subunits in the CNS, distribution noncompetitive (negative allosteric pattern 504-506 modulators) blockers 427-428,484 -- subunits, identified 499-502(tables) noradrenaline 317,704-706 - ion channel - nicotinic receptors, presynaptic -- ionic pore, structure at the amino 197-198 acid level 282-284 - release, nAChR activation 21 -- ionic selectivity 284-285 NRSF 59-60 -- rectification, mechanism governing nucleus accumbeus 15 288-289 -- single channel properties 285- olfactory tubercle 15 288 ondansetron 552-553 - ligand interaction, sites and open channel blockers 290-292 modulation 425-430 operant behaviour, nicotine effects -- ACh binding site 426 622-625 -- channel "activator" sites 425 peptides 706-708 -- nicotinic pharmacophore 425-426 4-oxystilbenes 435 -- transition states 425 - location in cholinergic and pancuronium 422(fig.) cholinoceptive cells 20-21 Parkinson's disease 487,755-758, - mediated facilitation of 759(table),780(table) neurotransmitter release, model - brain nAChRs 325-326 202(fig.) - movement difficulties, substantia nigra, - non-neuronal cells 164 dopamine release 144 - noninvasive exploration, in vivo 539- - nicotine, treatment 144,783-785,793 555 - nicotinic binding 232 -- [C] nicotine binding 545-549 patch clamp methods 301 -- functional brain imaging 540-541 pClamp 384 -- PET studies 541-545 312 -- receptor binding studies 539-540 pentamethonium 4 -- SPECT studies 541-545 sodium 422(fig.),428 -- studies, in vivo and ex vivo 540 422(fig.) - regulatory control by ligands 488(fig.) peptide toxins 434-435 - subtype classification 421 peripheral ganglia 17 820 Subject Index peripheral nervous system - {J3, neuronal bHLH transcription -AChRs factors regulation 47-49 -- distribution on the neural surface - nAChRs 39 176-180 -- adult 39-40 -- neuronal, functions 310-312 -- developing 40-41 PET studies 541-545,550,555,757 rivastigmine 553 427 RJR-1734 326-327 phenyltrimethylammonium (PTMA) RJR-2403 326,326-327,328, 420(fig.) 421 RJR-2557 420(fig.),439 phorbol 203-204 Ro31-8220 204 physostigmine 7, 420(fig.), 427 349 scaling factor 277 PMP 312 Schild method 383 positive allosteric modulators 436 schizophrenia 752-753,780(table) post-tetanic potentiation 258 - a-7 AChRs, role in 134 post-translational modification 403-407 - brain nAChRs 326 pre-pulse inhibition 660-661 -- binding 574 prednisolone 429 - nicotine, treatment 487,594,796-798 prepositus hipoglossal nucleus (PrH) - smoking 487 16 SCIP 68 presynaptic AChRs I extra synaptic scopolamine 783-784 AChRs 182 secobarbital 428 presynaptic receptors 317-323 seizures - electrophysiological detection 318- - a-4 nAChR induced 575-576 319(tables) - a-7 gene induced 576 procaine 428 - genetics of nicotinic receptors Profile of Mood States (POMS) 621, 575-579 647 -- animal studies 576-579 progressive supranuclear palsy, nicotinic -- human studies 575-576 binding 232 - naturally occurring 576 propranolol 593 - nicotine-induced 577-579 protein kinase C 203-204, 430 sensitization 661-664 Pseudopterogorgia toxin 80 - role in nicotine addiction 672 putative cholinergic systems 17 sensory ganglia, AChRs distribution pyridyl ethers 441 165 3-pyridyl-methylpyrrolidine (PMP) 609 serotonin 317,706,803 - release, nAChRs activation 21 quinacrine 291 serotonin type-3 receptor (5-HT3R) 47 QX-222 291 SIB-1508 420(fig.),785 SIB-1553A 326-327,420(fig.) rapsin 216 SIB-1765F 785 rat a3 promoter 66-68 small cell lung carcinoma 164,468, - activation by POU factor, SCIP 68 761-762 rat {J3 upstream region, transgenic - a-7 AChRs role 134 analysis 69 smoking see nicotine dependence; rat f34 enhancer 69-73 tobacco rat f34 promoter 65-66 smoking recombinant receptors, heterologous - animals 644-645 expression 394-396 - genetics 563-564 Renschau cells 6 -- influences, potential mechanisms reporter genes 43 564-566 REST 59-60 - passive 620 REST/NRSF factor 44-45 snake venom polypeptides retina 17 - snake-a-neurotoxins 461-462 Subject Index 821

- snake-k-neurotoxins 462-464 -- tolerance to nicotine, role of somatic spines vs. postsynaptic densities 670-672 252-254 tolerance 661 Sp-1 47 - acute 661-663,668-670 Sp-3 47 - behavioural 663, 667-668 SPECT studies 545, 555 - chronic 661-662,668-670 spinal cord motor nuclei 16 - humans, biochemical correlates 667 striatal interneurons 14-15 - pharmacodynamic 663 Stroop effect 787 Torpedo 82 383, 422(fig.), 435, 459-460 - receptor 34, 80 substance P 430 Tourette's syndrome 751-752, succinylcholine 422 (fig. ) 780(table) superior cervical ganglion, nicotine - brain nAChRs 326 paralysis 3 - mecamylamine 145,329 synaptic currents 250-252 - nicotine, treatment 144-145,785-786 toxins tacrine 553-554 - block motor activity, natural 89-91 Ta1-209 protein 482-483 - low molecular weight 456-461 tetramethylpiperidine 308 -- marine 460-461 tetrodoxin 317,321 -- plant 457-460 thromboxane A2 762 -- structure 456(fig.) TMP 312,314 trans-meta nicotine 439 tobacco transcriptional regulation, investigation - addiction 603 (technical tools) 43-44 - human use 563-566 trigeminal gangila 17 - psychopathology, use 582-585 trimethophan 383, 422(fig.), 616 -- auditory gating, animal models Tropidolaemus wagleri 89 574-575 kinase signalling pathways 205 -- mentally ill, prevalence of use 572- tyrphostin-23 205 573 -- schizophrenics, brain nAChRs ubiquitous transcription factor 46-47 binding 574 ulcerative colitis 765 - see nicotine dependence - tobacco use 145 - smoking -- cessation 802 venoms 89 -- model of nicotine dependence vesicular ACh transporter 13 710-715 vestibular ganglia 17 -- nicotine as the reinforcing principle voltage operated calcium channels, 648-649 calcium dependence 201-203 -- peripheral and non-nicotine factors, voltage-gated sodium channels 201 role of 649-650 -- physiological dependence, role of waglerin-1 89-91 678-680