Abstract
Rationale
While opioid withdrawal is typically studied under conditions of chronic (i.e., continuous) drug administration, withdrawal signs can also be demonstrated in both humans and animals after a single opioid exposure. This phenomenon, termed acute dependence, may be useful in understanding the early stages of opioid dependence and addiction.
Objective
This review provides an overview of acute dependence by comparing withdrawal from acute and chronic opioid exposure across dimensions ranging from symptomatology to neural substrates. Assessment of repeated withdrawals from acute opioid administration is also presented as a tool for better understanding the adaptive changes induced by multiple drug exposures.
Conclusions
Although not identical phenomena, acute and chronic dependence share a number of characteristics. Examining potentiations of withdrawal severity across multiple acute opioid exposures may be especially valuable in characterizing the development of drug dependence. Further study of acute dependence promises to lead to more effective treatments for opioid withdrawal and addiction.
Similar content being viewed by others
Notes
This review does not examine acute tolerance, or the diminished response to subsequent opioid administration following a single opioid exposure (Yano and Takemori 1977; Fairbanks and Wilcox 1997). While some authors assert that opioid tolerance and dependence reflect similar adaptive changes (Nielsen and Sparber 1985; but see Rahman et al. 1994; Kishioka et al. 2000), an attempt to synthesize the findings of acute dependence and acute tolerance studies falls beyond the scope of this review. In addition, although withdrawal also occurs following a single exposure to benzodiazepines (Bronson 1994) or alcohol (Morse et al. 2000), this review focuses solely on acute opioid dependence, which has been studied most extensively.
References
Abdelhamid EE, Sultana M, Portoghese PS, Takemori AE (1991) Selective blockage of delta opioid receptors prevents the development of morphine tolerance and dependence in mice. J Pharmacol Exp Ther 258:299–303
Adams JU, Holtzman SG (1990a) Pharmacologic characterization of the sensitization to the rate-decreasing effects of naltrexone induced by acute opioid pretreatment in rats. J Pharmacol Exp Ther 253:483–489
Adams JU, Holtzman SG (1990b) Tolerance and dependence after continuous morphine infusion from osmotic pumps measured by operant responding in rats. Psychopharmacology (Berl) 100:451–458
Adams JU, Holtzman SG (1991) Naltrexone-sensitizing effects of centrally administered morphine and opioid peptides. Eur J Pharmacol 193:67–73
Alheid GF, Heimer L (1988) New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39
Azar MR, Jones BC, Schulteis G (2003) Conditioned place aversion is a highly sensitive index of acute opioid dependence and withdrawal. Psychopharmacology (Berl) 170:42–50
Azar MR, Ahmed SH, Lintz R, Gutierrez T, Stinus L, Koob GF (2004) A non-invasive gating device for continuous drug delivery that allows control over the timing and duration of spontaneous opiate withdrawal. J Neurosci Methods 135:129–135
Azorlosa JL, Stitzer ML, Greenwald MK (1994) Opioid physical dependence development: effects of single versus repeated morphine pretreatments and of subjects’ opioid exposure history. Psychopharmacology (Berl) 114:71–80
Baeyens JM, Esposito E, Ossowska G, Samanin R (1987) Effects of peripheral and central administration of calcium channel blockers in the naloxone-precipitated abstinence syndrome in morphine-dependent rats. Eur J Pharmacol 137:9–13
Bals-Kubik R, Herz A, Shippenberg TS (1989) Evidence that the aversive effects of opioid antagonists and kappa-agonists are centrally mediated. Psychopharmacology (Berl) 98:203–206
Barrios M, Baeyens JM (1991) Differential effects of l-type calcium channel blockers and stimulants on naloxone-precipitated withdrawal in mice acutely dependent on morphine. Psychopharmacology (Berl) 104:397–403
Barthelemy C, Jacob J (1972) Naloxone precipitated abstinence after one single injection of morphine and effects of naloxone on single dose tolerance to morphine. J Pharmacol 3:530
Bear MF (2003) Bidirectional synaptic plasticity: from theory to reality. Philos Trans R Soc Lond B Biol Sci 358:649–655
Bickel WK, Stitzer ML, Liebson IA, Bigelow GE (1988) Acute physical dependence in man: effects of naloxone after brief morphine exposure. J Pharmacol Exp Ther 244:126–132
Bisaga A, Popik P (2000) In search of a new pharmacological treatment for drug and alcohol addiction: N-methyl-d-aspartate (NMDA) antagonists. Drug Alcohol Depend 59:1–15
Blanchard DC, Blanchard RJ (1988) Ethoexperimental approaches to the biology of emotion. Annu Rev Psychol 39:43–68
Blasig J, Herz A, Reinhold K, Zieglgansberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33:19–38
Bliss TV, Lomo T (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol 232:331–356
Brase DA, Iwamoto ET, Loh HH, Way EL (1976) Reinitiation of sensitivity to naloxone by a single narcotic injection in postaddicted mice. J Pharmacol Exp Ther 197:317–325
Brent PJ, Johnston PA, Chahl LA (1987) Plasma catecholamine concentrations during morphine withdrawal in conscious guinea-pigs. Clin Exp Pharmacol Physiol 14:623–631
Bronson ME (1994) Chlordiazepoxide, but not bretazenil, produces acute dependence, as evidenced by disruptions in schedule-controlled behavior. Pharmacol Biochem Behav 48:397–401
Caille S, Espejo EF, Reneric JP, Cador M, Koob GF, Stinus L (1999) Total neurochemical lesion of noradrenergic neurons of the locus coeruleus does not alter either naloxone-precipitated or spontaneous opiate withdrawal nor does it influence ability of clonidine to reverse opiate withdrawal. J Pharmacol Exp Ther 290:881–892
Ceger P, Kuhn CM (2000) Opiate withdrawal in the neonatal rat: relationship to duration of treatment and naloxone dose. Psychopharmacology (Berl) 150:253–259
Cheney DL, Goldstein A (1971) Tolerance to opioid narcotics: time course and reversibility of physical dependence in mice. Nature 232:477–478
Cicero TJ, Nock B, Meyer ER (1997) Sex-related differences in morphine’s antinociceptive activity: relationship to serum and brain morphine concentrations. J Pharmacol Exp Ther 282:939–944
Collier HO, Francis DL, Schneider C (1972) Modification of morphine withdrawal by drugs interacting with humoral mechanisms: some contradictions and their interpretation. Nature 237:220–223
Cowan A, Zhu XZ, Mosberg HI, Omnaas JR, Porreca F (1988) Direct dependence studies in rats with agents selective for different types of opioid receptor. J Pharmacol Exp Ther 246:950–955
Davis M, Astrachan DI (1978) Conditioned fear and startle magnitude: effects of different footshock or backshock intensities used in training. J Exp Psychol Anim Behav Processes 4:95–103
DeLander GE, Portoghese PS, Takemori AE (1984) Role of spinal mu opioid receptors in the development of morphine tolerance and dependence. J Pharmacol Exp Ther 231:91–96
Delfs JM, Zhu Y, Druhan JP, Aston-Jones G (2000) Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion. Nature 403:430–434
De Vries TJ, Shippenberg TS (2002) Neural systems underlying opiate addiction. J Neurosci 22:3321–3325
Dwoskin LP, Neal BS, Sparber SB (1983) Yohimbine exacerbates and clonidine attenuates acute morphine withdrawal in rats. Eur J Pharmacol 90:269–273
Easterling KW, Holtzman SG (1997) Intracranial self-stimulation in rats: sensitization to an opioid antagonist following acute or chronic treatment with mu opioid agonists. J Pharmacol Exp Ther 281:188–199
Easterling KW, Holtzman SG (1999) Discriminative stimulus effects of naltrexone after a single dose of morphine in the rat. J Pharmacol Exp Ther 288:1269–1277
Easterling KW, Holtzman SG (2004) In rats, acute morphine dependence results in antagonist-induced response suppression of intracranial self-stimulation. Psychopharmacology (Berl), Online First
Eisenberg RM (1982) Further studies on the acute dependence produced by morphine in opiate naive rats. Life Sci 31:1531–1540
Eisenberg RM (1983) Influence of clonidine on the acute dependence response elicited in naive rats by naloxone. Life Sci 32:1547–1552
Eisenberg RM (1985) Plasma corticosterone changes in response to central or peripheral administration of kappa and sigma opiate agonists. J Pharmacol Exp Ther 233:863–869
el-Kadi AO, Sharif SI (1998) The role of dopamine in the expression of morphine withdrawal. Gen Pharmacol 30:499–505
Fairbanks CA, Wilcox GL (1997) Acute tolerance to spinally administered morphine compares mechanistically with chronically induced morphine tolerance. J Pharmacol Exp Ther 282:1408–1417
Fanselow MS (1994) Neural organization of the defensive behavior system responsible for fear. Psychon Bull Rev 1:429–438
Fendt M, Mucha RF (2001) Anxiogenic-like effects of opiate withdrawal seen in the fear-potentiated startle test, an interdisciplinary probe for drug-related motivational states. Psychopharmacology (Berl) 155:242–250
Fukagawa Y, Katz JL, Suzuki T (1989) Effects of a selective kappa-opioid agonist, U-50,488H, on morphine dependence in rats. Eur J Pharmacol 170:47–51
Gellert VF, Sparber SB (1977) A comparison of the effects of naloxone upon body weight loss and suppression of fixed-ratio operant behavior in morphine-dependent rats. J Pharmacol Exp Ther 201:44–54
Goldberg SR, Schuster CR (1967) Conditioned suppression by a stimulus associated with nalorphine in morphine-dependent monkeys. J Exp Anal Behav 10:235–242
Goldberg SR, Woods JH, Schuster CR (1969) Morphine: conditioned increases in self-administration in rhesus monkeys. Science 166:1306–1307
Gomaa AA, Mohamed LH, Ahmed HN (1989) Modification of morphine-induced analgesia, tolerance and dependence by bromocriptine. Eur J Pharmacol 170:129–135
Gonzalvez ML, Milanes MV, Martinez-Pinero MG, Marin MT, Vargas ML (1994) Effects of intracerebroventricular clonidine on the hypothalamic noradrenaline and plasma corticosterone levels of opiate naive rats and after naloxone-induced withdrawal. Brain Res 647:199–203
Gracy KN, Dankiewicz LA, Koob GF (2001) Opiate withdrawal-induced fos immunoreactivity in the rat extended amygdala parallels the development of conditioned place aversion. Neuropsychopharmacology 24:152–160
Greenwald MK, June HL, Stitzer ML, Marco AP (1996) Comparative clinical pharmacology of short-acting mu opioids in drug abusers. J Pharmacol Exp Ther 277:1228–1236
Guo XH, Fairbanks CA, Stone LS, Loh HH (2003) DPDPE-UK14,304 synergy is retained in mu opioid receptor knockout mice. Pain 104:209–217
Harris AC, Gewirtz JC (2004) Elevated startle during withdrawal from acute morphine: a model of opiate withdrawal and anxiety. Psychopharmacology (Berl) 171:140–147
Harris AC, Atkinson DM, Hanes SL, Aase DM, Gewirtz JC (2003) Acute inactivation of the amygdala and bed nucleus of the stria terminalis blocks opiate withdrawal-potentiated startle in rats. Soc Neurosci Abstr online: # 110.4
Harris AC, Gallus NJ, Under S, Smith D, Gewirtz JC (2004a) Effects of the NMDA receptor antagonist memantine on acute opiate dependence as measured by withdrawal-potentiated startle and hyperalgesia. Soc Neurosci Abstr online: # 805.4
Harris AC, Hanes SL, Gewirtz JC (2004b) Potentiated startle and hyperalgesia during withdrawal from acute morphine: effects of multiple opiate exposures. Psychopharmacology (Berl) 176:266–273
Heinrichs SC, Menzaghi F, Schulteis G, Koob GF, Stinus L (1995) Suppression of corticotropin-releasing factor in the amygdala attenuates aversive consequences of morphine withdrawal. Behav Pharmacol 6:74–80
Heishman SJ, Stitzer ML, Bigelow GE, Liebson IA (1989a) Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval. I. J Pharmacol Exp Ther 250:485–491
Heishman SJ, Stitzer ML, Bigelow GE, Liebson IA (1989b) Acute opioid physical dependence in postaddict humans: naloxone dose effects after brief morphine exposure. J Pharmacol Exp Ther 248:127–134
Higgins GA, Sellers EM (1994) Antagonist-precipitated opioid withdrawal in rats: evidence for dissociations between physical and motivational signs. Pharmacol Biochem Behav 48:1–8
Holtzman SG (2003) Discrimination of a single dose of morphine followed by naltrexone: substitution of other agonists for morphine and other antagonists for naltrexone in a rat model of acute dependence. J Pharmacol Exp Ther 304:1033–1041
Hyman SE, Malenka RC (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat Rev Neurosci 2:695–703
Iwamoto ET (1981) Locomotor activity and antinociception after putative mu, kappa and sigma opioid receptor agonists in the rat: influence of dopaminergic agonists and antagonists. J Pharmacol Exp Ther 217:451–460
Jacob JJ, Michaud GM (1974) Acute physical dependence in the waking dog after a single low dose of morphine. Psychol Med 4:270–273
Jin C, Araki H, Nagata M, Suemaru K, Shibata K, Kawasaki H, Hamamura T, Gomita Y (2004) Withdrawal-induced c-Fos expression in the rat centromedial amygdala 24 h following a single morphine exposure. Psychopharmacology (Berl), Online First
Johnston J (1923) Further contributions to the study of the evolution of the forebrain. J Comp Neurol 35:337–481
Johnstone RE, Jobes DR, Kennell EM, Behar MG, Smith TC (1974) Reversal of morphine anesthesia with naloxone. Anesthesiology 41:361–367
Jones R (1980) Dependence in non-addict humans after a single dose of morphine. In: Way EL (ed) Endogenous and exogenous opiate agonists and antagonists. Pergamon Press, New York, pp 557–560
Jones RT (1981) Caffeine enhances morphine dependence in humans. In: Takagi H, Simon E (eds) Advances in endogenous and exogenous opioids. Elsevier, New York, pp 472–474
Jones KL, Zhu H, Jenab S, Du T, Inturrisi CE, Barr GA (2002) Attenuation of acute morphine withdrawal in the neonatal rat by the competitive NMDA receptor antagonist LY235959. Neuropsychopharmacology 26:301–310
June HL, Stitzer ML, Cone E (1995) Acute physical dependence: time course and relation to human plasma morphine concentrations. Clin Pharmacol Ther 57:270–280
Kalinichev M, Holtzman SG (2003) Changes in urination/defecation, auditory startle response, and startle-induced ultrasonic vocalizations in rats undergoing morphine withdrawal: similarities and differences between acute and chronic dependence. J Pharmacol Exp Ther 304:603–609
Kaneto H, Koida M, Nakanishi H (1972) Studies on physical dependence inducible by hours exposure of mice to morphine. Jpn J Pharmacol 22:755–766
Kest B, Lee CE, McLemore GL, Inturrisi CE (1996) An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice. Brain Res Bull 39:185–188
Kest B, Palmese CA, Hopkins E, Adler M, Juni A (2001) Assessment of acute and chronic morphine dependence in male and female mice. Pharmacol Biochem Behav 70:149–156
Kest B, Palmese CA, Hopkins E, Adler M, Juni A, Mogil JS (2002) Naloxone-precipitated withdrawal jumping in 11 inbred mouse strains: evidence for common genetic mechanisms in acute and chronic morphine physical dependence. Neuroscience 115:463–469
Kirby KC, Stitzer ML (1993) Opioid physical dependence development in humans: effect of time between agonist pretreatments. Psychopharmacology (Berl) 112:511–517
Kirby KC, Stitzer ML, Heishman SJ (1990) Acute opioid physical dependence in humans: effect of varying the morphine–naloxone interval II. J Pharmacol Exp Ther 255:730–737
Kishioka S, Paronis CA, Woods JH (2000) Acute dependence on, but not tolerance to, heroin and morphine as measured by respiratory effects in rhesus monkeys. Eur J Pharmacol 398:121–130
Kobayashi K, Manabe T, Takahashi T (1999) Calcium-dependent mechanisms involved in presynaptic long-term depression at the hippocampal mossy fibre-CA3 synapse. Eur J Neurosci 11:1633–1638
Koob GF (1999) The role of the striatopallidal and extended amygdala systems in drug addiction. In: McGinty JF (ed) Advancing from the ventral striatum to the extended amygdala: implications for neuropsychiatry and drug abuse (Ann NY Acad Sci, vol 877). New York Academy of Sciences, New York, pp 445–460
Koob GF, Le Moal M (1997) Drug abuse: hedonic homeostatic dysregulation. Science 278:52–58
Koob GF, Le Moal M (2001) Drug addiction, dysregulation of reward, and allostasis. Neuropsychopharmacology 24:97–129
Kosersky DS, Harris RA, Harris LS (1974) Naloxone-precipitated jumping activity in mice following the acute administration of morphine. Eur J Pharmacol 26:122–124
Kovacs GL, Acsai L, Tihanyi A, Telegdy G (1983) Catecholamine utilization in distinct mouse brain nuclei during acute morphine treatment, morphine tolerance and withdrawal syndrome. Eur J Pharmacol 93:149–158
Krystal JH, Redmond DE Jr (1983) A preliminary description of acute physical dependence on morphine in the vervet monkey. Pharmacol Biochem Behav 18:289–291
Larcher A, Laulin JP, Celerier E, Le Moal M, Simonnet G (1998) Acute tolerance associated with a single opiate administration: involvement of N-methyl-d-aspartate-dependent pain facilitatory systems. Neuroscience 84:583–589
Laulin JP, Larcher A, Celerier E, Le Moal M, Simonnet G (1998) Long-lasting increased pain sensitivity in rat following exposure to heroin for the first time. Eur J Neurosci 10:782–785
Liu J, Schulteis G (2004) Brain reward deficits accompany naloxone-precipitated withdrawal from acute opioid dependence. Pharmacol Biochem Behav 79:101–108
Liu J, McElfresh A, Reis S, Fuqua L, Schulteis G (2002) Neuroadaptive processes in limbic and basal forebrain reward circuitry contribute to acute opioid dependence, Soc Neurosci Abstr online: # 310.10
Lo FS, Mize RR (2002) Properties of LTD and LTP of retinocollicular synaptic transmission in the developing rat superior colliculus. Eur J Neurosci 15:1421–1432
Longnecker DE, Grazis PA, Eggers GW Jr (1973) Naloxone for antagonism of morphine-induced respiratory depression. Anesth Analg 52:447–453
Maj M, Turchan J, Smialowska M, Przewlocka B (2003) Morphine and cocaine influence on CRF biosynthesis in the rat central nucleus of amygdala. Neuropeptides 37:105–110
Maldonado R (1997) Participation of noradrenergic pathways in the expression of opiate withdrawal: biochemical and pharmacological evidence. Neurosci Biobehav Rev 21:91–104
Maldonado R, Mico JA, Valverde O, Saavedra MC, Leonsegui I, Gibert-Rahola J (1991) Influence of different benzodiazepines on the experimental morphine abstinence syndrome. Psychopharmacology 105:197–203
Maldonado R, Stinus L, Gold LH, Koob GF (1992) Role of different brain structures in the expression of the physical morphine withdrawal syndrome. J Pharmacol Exp Ther 261:669–677
Malinow R, Madison DV, Tsien RW (1988) Persistent protein kinase activity underlying long-term potentiation. Nature 335:820–824
Martin WR (1983) Pharmacology of opioids. Pharmacol Rev 35:283–323
Martin WR, Eades CG (1964) A comparison between acute and chronic physical dependence in the chronic spinal dog. J Pharmacol Exp Ther 146:385–394
Matthes HW, Maldonado R, Simonin F, Valverde O, Slowe S, Kitchen I, Befort K, Dierich A, Le Meur M, Dolle P, Tzavara E, Hanoune J, Roques BP, Kieffer BL (1996) Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the mu-opioid-receptor gene. Nature 383:819–823
McDonald RV, Parker LA, Siegel S (1997) Conditioned sucrose aversions produced by naloxone-precipitated withdrawal from acutely administered morphine. Pharmacol Biochem Behav 58:1003–1008
McLemore GL, Kest B, Inturrisi CE (1997) The effects of LY293558, an AMPA receptor antagonist, on acute and chronic morphine dependence. Brain Res 778:120–126
McNally GP, Akil H (2002) Role of corticotropin-releasing hormone in the amygdala and bed nucleus of the stria terminalis in the behavioral, pain modulatory, and endocrine consequences of opiate withdrawal. Neuroscience 112:605–617
Meyer DR, Sparber SB (1976) A comparison of withdrawal in rats implanted with different types of morphine pellets. Pharmacol Biochem Behav 5:603–607
Meyer DR, Sparber SB (1977) Evidence of possible opiate dependence during the behavioral depressant action of a single dose of morphine. Life Sci 21:1087–1093
Michalska E, Malec D (1993) Agonists and antagonists of adenosine receptors and morphine withdrawal syndrome in rats. Pol J Pharmacol 45:1–9
Miyamoto Y, Portoghese PS, Takemori AE (1993a) Involvement of delta 2 opioid receptors in acute dependence on morphine in mice. J Pharmacol Exp Ther 265:1325–1327
Miyamoto Y, Portoghese PS, Takemori AE (1993b) Involvement of delta 2 opioid receptors in the development of morphine dependence in mice. J Pharmacol Exp Ther 264:1141–1145
Morse AC, Schulteis G, Holloway FA, Koob GF (2000) Conditioned place aversion to the “hangover” phase of acute ethanol administration in the rat. Alcohol 22:19–24
Mucha RF (1987) Is the motivational effect of opiate withdrawal reflected by common somatic indices of precipitated withdrawal? A place conditioning study in the rat. Brain Res 418:214–220
Neal BS, Sparber SB (1986a) Ketanserin and pirenperone attenuate acute morphine withdrawal in rats. Eur J Pharmacol 132:299–304
Neal BS, Sparber SB (1986b) Mianserin attenuates naloxone-precipitated withdrawal signs in rats acutely or chronically dependent upon morphine. J Pharmacol Exp Ther 236:157–165
Nestler EJ (1996) Under siege: the brain on opiates. Neuron 16:897–900
Nestler EJ (2001) Molecular neurobiology of addiction. Am J Addict 10:201–217
Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278:58–63
Nielsen JA, Sparber SB (1985) Indomethacin facilitates acute tolerance to and dependence upon morphine as measured by changes in fixed-ratio behavior and rectal temperature in rats. Pharmacol Biochem Behav 22:921–931
Nutt JG, Jasinski DR (1974) Methadone–naloxone mixtures for use in methadone maintenance programs. I. An evaluation in man of their pharmacological feasibility. II. Demonstration of acute physical dependence. Clin Pharmacol Ther 15:156–166
O’Brien CP, Testa T, O’Brien TJ, Brady JP, Wells B (1977) Conditioned narcotic withdrawal in humans. Science 195:1000–1002
Parker LA, Joshi A (1998) Naloxone-precipitated morphine withdrawal induced place aversions: effect of naloxone at 24 hours postmorphine. Pharmacol Biochem Behav 61:331–333
Parker LA, Cyr JA, Santi AN, Burton PD (2002) The aversive properties of acute morphine dependence persist 48 h after a single exposure to morphine: evaluation by taste and place conditioning. Pharmacol Biochem Behav 72:87–92
Popik P, Danysz W (1997) Inhibition of reinforcing effects of morphine and motivational aspects of naloxone-precipitated opioid withdrawal by N-methyl-d-aspartate receptor antagonist, memantine. J Pharmacol Exp Ther 280:854–865
Popik P, Mamczarz J, Fraczek M, Widla M, Hesselink M, Danysz W (1998) Inhibition of reinforcing effects of morphine and naloxone-precipitated opioid withdrawal by novel glycine site and uncompetitive NMDA receptor antagonists. Neuropharmacology 37:1033–1042
Punch LJ, Self DW, Nestler EJ, Taylor JR (1997) Opposite modulation of opiate withdrawal behaviors on microinfusion of a protein kinase A inhibitor versus activator into the locus coeruleus or periaqueductal gray. J Neurosci 17:8520–8527
Rahman AF, Takahashi M, Kaneto H (1994) Morphine dependence with or without tolerance in formalin-treated mice: further evidence for the dissociation. Jpn J Pharmacol 66:277–280
Ramabadran K (1982) Effects of N-methylnaloxone and N-methylnaltrexone on nociception and precipitated abstinence in mice. Life Sci 31:1253–1256
Ramabadran K (1983) Naloxone-precipitated abstinence in mice, rats and gerbils acutely dependent on morphine. Life Sci 33:385–388
Ramabadran K (1985) An analysis of precipitated withdrawal in rats acutely dependent on morphine. Jpn J Pharmacol 37:307–316
Ramaswamy S, Bapna JS (1987) Antagonism of morphine tolerance and dependence by metoclopramide. Life Sci 40:807–810
Ritzmann RF (1981) Opiate dependence following acute injections of morphine and naloxone: the assessment of various withdrawal signs. Pharmacol Biochem Behav 14:575–577
Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291
Schaefer GJ, Michael RP (1986) Changes in response rates and reinforcement thresholds for intracranial self-stimulation during morphine withdrawal. Pharmacol Biochem Behav 25:1263–1269
Scherrer G, Befort K, Contet C, Becker J, Matifas A, Kieffer BL (2004) The delta agonists DPDPE and deltorphin II recruit predominantly mu receptors to produce thermal analgesia: a parallel study of mu, delta and combinatorial opioid receptor knockout mice. Eur J Neurosci 19:2239–2248
Schindler CW, Wu XZ, Su TP, Goldberg SR, Katz JL (1990) Enhanced sensitivity to behavioral effects of naltrexone in rats. J Pharmacol Exp Ther 252:8–14
Schnur P (1991) Acute morphine dependence in the hamster. Pharmacol Biochem Behav 38:711–713
Schnur P, Espinoza M, Flores R, Ortiz S, Vallejos S, Wainwright M (1992) Blocking naloxone-precipitated withdrawal in rats and hamsters. Pharmacol Biochem Behav 43:1093–1098
Schreiber S, Backler MM, Herman I, Shamir D, Rigai T, Bar-Hamburger R, Pick CG (2003) Mianserin and trazodone significantly attenuate the intensity of opioid withdrawal symptoms in mice. Addict Biol 8:107–114
Schulteis G, Koob GF (1996) Reinforcement processes in opiate addiction: a homeostatic model. Neurochem Res 21:1437–1454
Schulteis G, Markou A, Gold LH, Stinus L, Koob GF (1994) Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. J Pharmacol Exp Ther 271:1391–1398
Schulteis G, Heyser CJ, Koob GF (1997) Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure. Psychopharmacology (Berl) 129:56–65
Schulteis G, Yackey M, Risbrough V, Koob GF (1998) Anxiogenic-like effects of spontaneous and naloxone-precipitated opiate withdrawal in the elevated plus-maze. Pharmacol Biochem Behav 60:727–731
Schulteis G, Heyser CJ, Koob GF (1999) Differential expression of response-disruptive and somatic indices of opiate withdrawal during the initiation and development of opiate dependence. Behav Pharmacol 10:235–242
Schulteis G, Morse AC, Liu J (2003) Repeated experience with naloxone facilitates acute morphine withdrawal: potential role for conditioning processes in acute opioid dependence. Pharmacol Biochem Behav 76:493–503
Schulteis G, Morse AC, Liu J (2004) Conditioning processes contribute to severity of naloxone-precipitated withdrawal from acute opioid dependence. Psychopharmacology (Berl), Online First
Sharif SI, El-Kadi AO (1996) Modification of naloxone-precipitated withdrawal symptoms in mice by drugs acting on alpha(2)-adrenoceptors. Behav Pharmacol 7:334–340
Simonin F, Valverde O, Smadja C, Slowe S, Kitchen I, Dierich A, Le Meur M, Roques BP, Maldonado R, Kieffer BL (1998) Disruption of the kappa-opioid receptor gene in mice enhances sensitivity to chemical visceral pain, impairs pharmacological actions of the selective kappa-agonist U-50,488H and attenuates morphine withdrawal. EMBO J 17:886–897
Smits SE (1975) Quantitation of physical dependence in mice by naloxone-precipitated jumping after a single dose of morphine. Res Commun Chem Pathol Pharmacol 10:651–661
Sparber SB, Gellert VF, Lichtblau L, Eisenberg R (1978) The use of operant behavior methods to study aggression and effects of acute and chronic morphine administration in rats. In: Adler MW, Manara L, Samanin R (eds) Factors affecting the action of narcotics. Raven Press, New York, pp 63–91
Stinus L, Le Moal M, Koob GF (1990) Nucleus accumbens and amygdala are possible substrates for the aversive stimulus effects of opiate withdrawal. Neuroscience 37:767–773
Suzuki T, Ikeda H, Tsuji M, Misawa M, Narita M, Tseng LF (1997) Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice. Life Sci 61:PL 165–170
Sweatt JD (1999) Toward a molecular explanation for long-term potentiation. Learn Mem 6:399–416
Tavani A, Bianchi G, Manara L (1979) Morphine no longer blocks gastrointestinal transit but retains antinociceptive action in diallylnormorphine-pretreated rats. Eur J Pharmacol 59:151–154
Thomas MJ, Beurrier C, Bonci A, Malenka RC (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci 4:1217–1223
Trujillo KA (2000) Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical studies. Psychopharmacology (Berl) 151:121–141
Ungless MA, Whistler JL, Malenka RC, Bonci A (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411:583–587
Valeri P, Martinelli B, Pimpinella G, Severini C (1989) Effects of dapiprazole, clonidine and yohimbine on the development of dependence and withdrawal behaviour in mice. Drug Alcohol Depend 23:73–77
Valeri P, Pimpinella G, Troiani MP, Morrone LA, Romanelli L (1991) Effects of trazodone and m-chlorophenylpiperazine (m-CPP) on acute dependence in mice. Brain Res Bull 26:799–802
Vivian JA, Miczek KA (1991) Ultrasounds during morphine withdrawal in rats. Psychopharmacology (Berl) 104:187–193
Walker DL, Cassella JV, Lee Y, De Lima TC, Davis M (1997) Opposing roles of the amygdala and dorsolateral periaqueductal gray in fear-potentiated startle. Neurosci Biobehav Rev 21:743–753
Walker JR, Ahmed SH, Gracy KN, Koob GF (2000) Microinjections of an opiate receptor antagonist into the bed nucleus of the stria terminalis suppress heroin self-administration in dependent rats. Brain Res 854:85–92
Wang Z, Bilsky EJ, Porreca F, Sadee W (1994) Constitutive mu opioid receptor activation as a regulatory mechanism underlying narcotic tolerance and dependence. Life Sci 54:PL339–PL350
Wei E, Loh H (1972) Morphine physical dependence unaltered by previous dependence on morphine. Nature 238:396–397
White-Gbadebo D, Holtzman S (1994a) Naloxone pretreatment blocks acute morphine-induced sensitization to naltrexone. Psychopharmacology (Berl) 114:225–228
White-Gbadebo D, Holtzman SG (1994b) Acute sensitization to opioid antagonists. Pharmacol Biochem Behav 47:559–566
Wikler A (1973) Dynamics of drug dependence. Implications of a conditioning theory for research and treatment. Arch Gen Psychiatry 28:611–616
Wikler A, Carter RL (1953) Effects of single doses of N-allylnormorphine on hindlimb reflexes of chronic spinal dogs during cycles of morphine addiction. J Pharmacol Exp Ther 109:92–101
Wiley JN, Downs DA (1979) Naloxone-precipitated jumping in mice pretreated with acute injections of opioids. Life Sci 25:797–801
Williams JT, Christie MJ, Manzoni O (2001) Cellular and synaptic adaptations mediating opioid dependence. Physiol Rev 81:299–343
Wong CL, Bentley CA (1978a) Increased antagonist potency of naloxone caused by morphine pretreatment in mice. Eur J Pharmacol 47:415–422
Wong CL, Bentley GA (1978) The role of the cholinergic system in the development of increased naloxone potency in mice. Eur J Pharmacol 50:221–230
Wong CL, Bentley GA (1980) The effects of cholinergic compounds on the development of morphine tolerance, dependence and increased naloxone potency in mice. Eur J Pharmacol 61:99–109
Yamamoto H, Harris RA, Loh HH, Way EL (1978) Effects of acute and chronic morphine treatments on calcium localization and binding in brain. J Pharmacol Exp Ther 205:255–264
Yano I, Takemori AE (1977) Inhibition by naloxone of tolerance and dependence in mice treated acutely and chronically with morphine. Res Commun Chem Pathol Pharmacol 16:721–734
Yano I, Nishino H, Murano T (1979) Antagonism by naloxone of tolerance and dependence in mice given a single dose of morphine. Jpn J Pharmacol 29:357–366
Young AM (1986) Effects of acute morphine pretreatment on the rate-decreasing and antagonist activity of naloxone. Psychopharmacology 88:201–208
Zarrindast MR, Habibi M, Borzabadi S, Fazli-Tabaei S, Hossein Yahyavi S, Rostamin P (2002) The effects of dopamine receptor agents on naloxone-induced jumping behaviour in morphine-dependent mice. Eur J Pharmacol 451:287–293
Zhu H, Barr GA (2000) Naltrexone-precipitated morphine withdrawal in infant rat is attenuated by acute administration of NOS inhibitors but not NMDA receptor antagonists. Psychopharmacology (Berl) 150:325–336
Zhu H, Barr GA (2001) Inhibition of morphine withdrawal by the NMDA receptor antagonist MK-801 in rat is age-dependent. Synapse 40:282–293
Acknowledgements
This work was supported by the National Institute of Drug Abuse T32 DA 07097 and the University of Minnesota.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Harris, A.C., Gewirtz, J.C. Acute opioid dependence: characterizing the early adaptations underlying drug withdrawal. Psychopharmacology 178, 353–366 (2005). https://doi.org/10.1007/s00213-005-2155-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-005-2155-0