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Reverse tolerance

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that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.. ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
206:, this can then put this group at risk of intoxication when drinking even very small amounts of alcohol. Sensitization, a form of reverse tolerance, develops rapidly to the positive, euphoric effects of alcohol, but not to the physical effects, such as sedation and respiratory depression, which diminish with prolonged use. This sensitization does not occur, however, with administration of benzodiazepines or neuroactive steroids, which only exhibit weakening of effect with repeated use. 430: 202:, in which the effect or the subject's reaction decreases following its repeated use. The two notions are not incompatible, and tolerance may sometimes lead to reverse tolerance. For example, heavy drinkers initially develop tolerance to alcohol, requiring them to drink larger amounts to achieve a similar effect, but as excessive drinking can cause 369:
Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification
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Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to
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Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use,
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Reverse tolerance can also occur in users of stimulants such as cocaine or amphetamines. A previously recreational dose may become enough to cause psychosis in regular users, or users who previously had a psychotic episode may be more likely to have one in the future and at lower doses once drug
50:– psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain 195:
phenomenon describing subjects' increased reaction (positive or negative) to a drug following its repeated use. Not all drugs are subject to reverse tolerance.
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meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.
171: 236: 105:– dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome) 61:– an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake) 471: 256:
Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.).
265: 139:– a condition in which the use of substances leads to clinically and functionally significant impairment or distress 164: 231: 490: 495: 157: 382: 226: 123:– stimuli that the brain interprets as intrinsically positive and desirable or as something to approach 464: 101: 135: 457: 445: 57: 8: 147:– the diminishing effect of a drug resulting from repeated administration at a given dose 85: 73:– the escalating effect of a drug resulting from repeated administration at a given dose 352: 327: 299: 282: 357: 304: 261: 347: 339: 294: 94: 213:
In some cases drug sensitization may also refer to medical interventions (e.g. a
77: 35: 410: 441: 199: 143: 114:– stimuli that increase the probability of repeating behaviors paired with them 39: 484: 127: 118: 109: 51: 131:– an amplified response to a stimulus resulting from repeated exposure to it 437: 361: 308: 214: 203: 192: 343: 90: 46: 30: 258:
Molecular Neuropharmacology: A Foundation for Clinical Neuroscience
328:"Neurobiologic Advances from the Brain Disease Model of Addiction" 260:(2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. 217:) that aim to reduce the insensitivity caused by drug tolerance. 429: 38:
disorder characterized by persistent use of drugs (including
396: 81:– symptoms that occur upon cessation of repeated drug use 255: 42:) despite substantial harm and adverse consequences 325: 249: 482: 326:Volkow ND, Koob GF, McLellan AT (January 2016). 89:– dependence that involves persistent physical– 465: 274: 165: 319: 472: 458: 383:"Reverse tolerance and drug sensitization" 280: 172: 158: 351: 298: 283:"Cellular basis of memory for addiction" 237:Kindling (sedative–hypnotic withdrawal) 93:withdrawal symptoms (e.g., fatigue and 483: 424: 411:"Chronic Amphetamine Use and Abuse" 13: 287:Dialogues in Clinical Neuroscience 14: 507: 370:of severe substance-use disorder. 22:Addiction and dependence glossary 428: 332:New England Journal of Medicine 232:Downregulation and upregulation 403: 389: 375: 1: 242: 444:. You can help Knowledge by 397:"What Is Reverse Tolerance?" 281:Nestler EJ (December 2013). 7: 220: 10: 512: 423: 227:Desensitization (medicine) 16:Pharmacological phenomenon 153: 26: 21: 198:This is the opposite of 102:psychological dependence 440:-related article is a 136:substance use disorder 344:10.1056/NEJMra1511480 491:Substance dependence 86:physical dependence 496:Pharmacology stubs 189:drug sensitization 66:drug sensitization 453: 452: 210:usage continues. 185:Reverse tolerance 182: 181: 71:reverse tolerance 503: 474: 467: 460: 432: 425: 415: 414: 407: 401: 400: 393: 387: 386: 379: 373: 372: 355: 323: 317: 316: 302: 278: 272: 271: 253: 174: 167: 160: 95:delirium tremens 19: 18: 511: 510: 506: 505: 504: 502: 501: 500: 481: 480: 479: 478: 421: 419: 418: 409: 408: 404: 395: 394: 390: 381: 380: 376: 368: 324: 320: 279: 275: 268: 254: 250: 245: 223: 193:pharmacological 178: 78:drug withdrawal 36:biopsychosocial 17: 12: 11: 5: 509: 499: 498: 493: 477: 476: 469: 462: 454: 451: 450: 433: 417: 416: 402: 388: 374: 338:(4): 363–371. 318: 293:(4): 431–443. 273: 266: 247: 246: 244: 241: 240: 239: 234: 229: 222: 219: 200:drug tolerance 180: 179: 177: 176: 169: 162: 154: 151: 150: 149: 148: 140: 132: 124: 115: 106: 98: 82: 74: 62: 54: 52:reward systems 47:addictive drug 43: 24: 23: 15: 9: 6: 4: 3: 2: 508: 497: 494: 492: 489: 488: 486: 475: 470: 468: 463: 461: 456: 455: 449: 447: 443: 439: 434: 431: 427: 426: 422: 412: 406: 398: 392: 384: 378: 371: 363: 359: 354: 349: 345: 341: 337: 333: 329: 322: 315: 310: 306: 301: 296: 292: 288: 284: 277: 269: 267:9780071481274 263: 259: 252: 248: 238: 235: 233: 230: 228: 225: 224: 218: 216: 211: 207: 205: 201: 196: 194: 190: 186: 175: 170: 168: 163: 161: 156: 155: 152: 146: 145: 141: 138: 137: 133: 130: 129: 128:sensitization 125: 122: 120: 116: 113: 111: 107: 104: 103: 99: 96: 92: 88: 87: 83: 80: 79: 75: 72: 68: 67: 63: 60: 59: 55: 53: 49: 48: 44: 41: 37: 33: 32: 28: 27: 25: 20: 446:expanding it 438:pharmacology 435: 420: 405: 391: 377: 365: 335: 331: 321: 312: 290: 286: 276: 257: 251: 215:drug holiday 212: 208: 204:liver damage 197: 188: 184: 183: 142: 134: 126: 117: 108: 100: 84: 76: 70: 65: 64: 56: 45: 29: 110:reinforcing 485:Categories 243:References 58:dependence 144:tolerance 119:rewarding 31:addiction 362:26816013 309:24459410 221:See also 353:6135257 300:3898681 121:stimuli 112:stimuli 91:somatic 40:alcohol 360:  350:  307:  297:  264:  436:This 191:is a 442:stub 358:PMID 305:PMID 262:ISBN 34:– a 348:PMC 340:doi 336:374 295:PMC 187:or 69:or 487:: 364:. 356:. 346:. 334:. 330:. 311:. 303:. 291:15 289:. 285:. 473:e 466:t 459:v 448:. 413:. 399:. 385:. 342:: 270:. 173:e 166:t 159:v 97:)

Index

addiction
biopsychosocial
alcohol
addictive drug
reward systems
dependence
drug sensitization
drug withdrawal
physical dependence
somatic
delirium tremens
psychological dependence
reinforcing
rewarding
sensitization
substance use disorder
tolerance
v
t
e
pharmacological
drug tolerance
liver damage
drug holiday
Desensitization (medicine)
Downregulation and upregulation
Kindling (sedative–hypnotic withdrawal)
ISBN
9780071481274
"Cellular basis of memory for addiction"

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