Affective and Neuroendocrine Effects of Withdrawal from Chronic, Long-acting Opiate Administration

Overview

Journal Brain Res

Specialty Neurology

Date 2013 Oct 1

PMID 24076207

Citations 6

Authors

Kathryn L Hamilton

Andrew C Harris

Jonathan C Gewirtz

Affiliations

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Abstract

Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about the effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure - in contrast to withdrawal from acute drug exposure - but rather is manifested as exaggerated fear in response to explicit threat cues.

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References

Rothwell P, Gewirtz J, Thomas M . Episodic withdrawal promotes psychomotor sensitization to morphine. Neuropsychopharmacology. 2010; 35(13):2579-89. PMC: 3055568. DOI: 10.1038/npp.2010.134. View

Kronfeld-Schor N, Einat H . Circadian rhythms and depression: human psychopathology and animal models. Neuropharmacology. 2011; 62(1):101-14. DOI: 10.1016/j.neuropharm.2011.08.020. View

Hamilton K, Harris A, Gewirtz J, Sparber S, Schrott L . HPA axis dysregulation following prenatal opiate exposure and postnatal withdrawal. Neurotoxicol Teratol. 2005; 27(1):95-103. DOI: 10.1016/j.ntt.2004.09.004. View

Geyer M, Swerdlow N . Measurement of startle response, prepulse inhibition, and habituation. Curr Protoc Neurosci. 2008; Chapter 8:Unit 8.7. DOI: 10.1002/0471142301.ns0807s03. View

Frankland P, Ralph M . Circadian modulation in the rat acoustic startle circuit. Behav Neurosci. 1995; 109(1):43-8. DOI: 10.1037//0735-7044.109.1.43. View

Grillon C . Startle reactivity and anxiety disorders: aversive conditioning, context, and neurobiology. Biol Psychiatry. 2002; 52(10):958-75. DOI: 10.1016/s0006-3223(02)01665-7. View

Pinter-Kubler B, Ferenczi S, Nunez C, Zelei E, Polyak A, Milanes M . Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal. PLoS One. 2013; 8(6):e67027. PMC: 3689674. DOI: 10.1371/journal.pone.0067027. View

Kreek M . Methadone-related opioid agonist pharmacotherapy for heroin addiction. History, recent molecular and neurochemical research and future in mainstream medicine. Ann N Y Acad Sci. 2000; 909:186-216. DOI: 10.1111/j.1749-6632.2000.tb06683.x. View

Young G, Steinfels G, KHAZAN N . Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine. Pharmacol Biochem Behav. 1979; 10(4):585-9. DOI: 10.1016/0091-3057(79)90237-5. View

10.

Schulteis G, Markou A, GOLD L, Stinus L, Koob G . Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis. J Pharmacol Exp Ther. 1994; 271(3):1391-8. View

11.

Walker D, Davis M . Involvement of the dorsal periaqueductal gray in the loss of fear-potentiated startle accompanying high footshock training. Behav Neurosci. 1997; 111(4):692-702. DOI: 10.1037//0735-7044.111.4.692. View

12.

Kalinichev M, Holtzman S . 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. 2003; 304(2):603-9. DOI: 10.1124/jpet.102.044206. View

13.

Jonkman S, Risbrough V, Geyer M, Markou A . Spontaneous nicotine withdrawal potentiates the effects of stress in rats. Neuropsychopharmacology. 2007; 33(9):2131-8. PMC: 2648847. DOI: 10.1038/sj.npp.1301607. View

14.

Strain E, Bigelow G, Liebson I, Stitzer M . Moderate- vs high-dose methadone in the treatment of opioid dependence: a randomized trial. JAMA. 1999; 281(11):1000-5. DOI: 10.1001/jama.281.11.1000. View

15.

Young E, Haskett R, Grunhaus L, Pande A, Weinberg V, Watson S . Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients. Arch Gen Psychiatry. 1994; 51(9):701-7. DOI: 10.1001/archpsyc.1994.03950090033005. View

16.

Becker G, Gerak L, Koek W, France C . Antagonist-precipitated and discontinuation-induced withdrawal in morphine-dependent rhesus monkeys. Psychopharmacology (Berl). 2008; 201(3):373-82. PMC: 3449323. DOI: 10.1007/s00213-008-1293-6. View

17.

Stinus L, Robert C, Karasinski P, Limoge A . Continuous quantitative monitoring of spontaneous opiate withdrawal: locomotor activity and sleep disorders. Pharmacol Biochem Behav. 1998; 59(1):83-9. DOI: 10.1016/s0091-3057(97)00319-5. View

18.

Nilsson M, ANGGARD E, Holmstrand J, Gunne L . Pharmacokinetics of methadone during maintenance treatment: adaptive changes during the induction phase. Eur J Clin Pharmacol. 1982; 22(4):343-9. DOI: 10.1007/BF00548404. View

19.

Rothwell P, Thomas M, Gewirtz J . Distinct profiles of anxiety and dysphoria during spontaneous withdrawal from acute morphine exposure. Neuropsychopharmacology. 2009; 34(10):2285-95. PMC: 2726902. DOI: 10.1038/npp.2009.56. View

20.

Cobuzzi J, Riley A . Spontaneous withdrawal in opiate-dependent Fischer 344, Lewis and Sprague-Dawley rats. Pharmacol Biochem Behav. 2010; 98(1):28-34. DOI: 10.1016/j.pbb.2010.12.003. View