Home LiteratureArticle Details
PMID: 10531460 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A single exposure to amphetamine is sufficient to induce long-term behavioral, neuroendocrine, and neurochemical sensitization in rats.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 19 ·No. 21 ·1999-11-01 ·Pages 9579-86

Vanderschuren LJ, Schmidt ED, De Vries TJ, Van Moorsel CA, Tilders FJ, Schoffelmeer AN

Abstract

Repeated treatment with psychostimulant drugs causes long-lasting behavioral sensitization and associated neuroadaptations. Although sensitization induced by a single psychostimulant exposure has also been reported, information on the behavioral and neurochemical consequences of a single psychostimulant exposure is sparse. Therefore, to evaluate whether behavioral sensitization evoked by single and repeated psychostimulant pretreatment regimens represent the same neurobiological phenomenon, the time-dependent expression of behavioral, neurochemical, and neuroendocrine sensitization after a single exposure to amphetamine was investigated in rats. A single exposure to amphetamine (5 mg/kg, i.p.) caused context-independent sensitization of the locomotor effects of amphetamine, which intensified over time. Thus, sensitization to amphetamine was marginal at 3 d after treatment and more evident after 1 week, whereas 3 weeks after treatment, profound sensitization, as well as cross-sensitization, to cocaine was observed. Amphetamine pretreatment caused an increase in the electrically evoked release of [(3)H]dopamine from nucleus accumbens, caudate putamen, and medial prefrontal cortex slices and of [(14)C]acetylcholine from accumbens and caudate slices. The hyperreactivity of dopaminergic nerve terminals appeared to parallel the development of locomotor sensitization, i.e., whereas hyperreactivity of accumbens dopaminergic terminals increased between 3 d and 3 weeks after treatment, the hyperreactivity of medial prefrontal dopaminergic terminals decreased. Pre-exposure to amphetamine also sensitized the hypothalamus-pituitary-adrenal axis response to amphetamine at 1 and 3 weeks, but not at 3 d after treatment. Because these data closely resemble those reported previously for repeated amphetamine pretreatment, it is concluded that a single exposure to amphetamine is sufficient to induce long-term behavioral, neurochemical, and neuroendocrine sensitization in rats.

MeSH Terms
Acetylcholine/metabolism Adrenocorticotropic Hormone/blood,metabolism Amphetamine/administration & dosage,pharmacology Animals Benzazepines/pharmacology Carrier Proteins/agonists,physiology Caudate Nucleus/drug effects,physiology Cocaine/pharmacology Corticosterone/blood,metabolism Dopamine/metabolism Dopamine Agonists/pharmacology Hypothalamo-Hypophyseal System/drug effects,physiology In Vitro Techniques Injections, Intraperitoneal Male Motor Activity/drug effects Nucleus Accumbens/drug effects,physiology Pituitary-Adrenal System/drug effects,physiology Prefrontal Cortex/drug effects,physiology Putamen/drug effects,physiology Rats Rats, Wistar Receptors, Dopamine/physiology Receptors, Drug/agonists,physiology Time Factors
Chemicals
Benzazepines Carrier Proteins Dopamine Agonists Receptors, Dopamine Receptors, Drug cocaine receptor SK&F 82958 Adrenocorticotropic Hormone Amphetamine Cocaine Acetylcholine Dopamine Corticosterone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Vanderschuren L J
Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, 1081 BT Amsterdam, The Netherlands.
Schmidt E D
De Vries T J
Van Moorsel C A
Tilders F J
Schoffelmeer A N
References (66)
66 references, click to expand
  1. Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine.
    Psychopharmacology (Berl). 1997 Dec;134(3):266-76 PMID: 9438676
  2. Opposed Behavioural Outputs of Increased Dopamine Transmission in Prefrontocortical and Subcortical Areas: A Role for the Cortical D-1 Dopamine Receptor.
    Eur J Neurosci. 1991;3(10):1001-1007 PMID: 12106258
  3. Opposite influences of dopaminergic pathways to the prefrontal cortex or the septum on the dopaminergic transmission in the nucleus accumbens. An in vivo voltammetric study.
    Neuroscience. 1989;29(1):45-56 PMID: 2710347
  4. Modulation of the induction or expression of psychostimulant sensitization by the circumstances surrounding drug administration.
    Neurosci Biobehav Rev. 1998 Mar;22(2):347-54 PMID: 9579324
  5. Intermittent morphine treatment causes a protracted increase in cholinergic striatal neurotransmission measured ex vivo.
    Eur J Pharmacol. 1995 Nov 24;286(3):311-4 PMID: 8608794
  6. Striatal acetylcholine release correlates with behavioral sensitization in rats withdrawn from chronic amphetamine.
    J Pharmacol Exp Ther. 1997 Aug;282(2):818-26 PMID: 9262346
  7. Glucocorticoid and mineralocorticoid receptors differentially modulate cultured dopaminergic neurons of rat ventral mesencephalon.
    Eur J Pharmacol. 1994 Sep 22;263(1-2):149-56 PMID: 7821346
  8. Presynaptic nicotinic modulation of dopamine release in the three ascending pathways studied by in vivo microdialysis: comparison of naive and chronic nicotine-treated rats.
    J Neurochem. 1997 Apr;68(4):1511-9 PMID: 9084421
  9. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants.
    Brain Res Brain Res Rev. 1997 Oct;25(2):192-216 PMID: 9403138
  10. Time course of the development of the enhanced behavioral and biochemical responses to amphetamine after pretreatment with amphetamine.
    Neuropharmacology. 1985 Sep;24(9):823-9 PMID: 4058677
  11. Enduring changes in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis.
    Brain Res. 1986 Jun;396(2):157-98 PMID: 3527341
  12. AMPA-receptors are involved in the expression of amphetamine-induced behavioural sensitisation, but not in the expression of amphetamine-induced conditioned activity in mice.
    Neuropharmacology. 1998 Sep;37(9):1131-8 PMID: 9833643
  13. Induction but not expression of behavioural sensitization to nicotine in the rat is dependent on glucocorticoids.
    Eur J Pharmacol. 1995 Mar 24;276(1-2):155-64 PMID: 7781685
  14. Involvement of N-methyl-D-aspartate receptor stimulation in the ventral tegmental area and amygdala in behavioral sensitization to cocaine.
    J Pharmacol Exp Ther. 1993 Oct;267(1):486-95 PMID: 8229779
  15. Dopamine displays an identical apparent affinity towards functional dopamine D1 and D2 receptors in rat striatal slices: possible implications for the regulatory role of D2 receptors.
    Synapse. 1994 Jul;17(3):190-5 PMID: 7974202
  16. Modulation of the locomotor response to amphetamine by corticosterone.
    Neuroscience. 1993 Oct;56(4):981-8 PMID: 8284048
  17. Glucocorticoids and behavioral effects of psychostimulants. I: locomotor response to cocaine depends on basal levels of glucocorticoids.
    J Pharmacol Exp Ther. 1997 Jun;281(3):1392-400 PMID: 9190875
  18. Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine.
    J Neurosci. 1994 May;14(5 Pt 1):2724-31 PMID: 8182438
  19. Amphetamine-induced time-dependent sensitization of dopamine neurotransmission in the dorsal and ventral striatum: a microdialysis study in behaving rats.
    Synapse. 1995 Jan;19(1):56-65 PMID: 7709344
  20. Development of both conditioning and sensitization of the behavioral activating effects of amphetamine is blocked by the non-competitive NMDA receptor antagonist, MK-801.
    Psychopharmacology (Berl). 1993;110(1-2):125-32 PMID: 7870871
  21. Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats.
    Psychopharmacology (Berl). 1991;103(4):480-92 PMID: 2062986
  22. Persistent structural modifications in nucleus accumbens and prefrontal cortex neurons produced by previous experience with amphetamine.
    J Neurosci. 1997 Nov 1;17(21):8491-7 PMID: 9334421
  23. Behavioral sensitization: characterization of enduring changes in rotational behavior produced by intermittent injections of amphetamine in male and female rats.
    Psychopharmacology (Berl). 1984;84(4):466-75 PMID: 6441946
  24. Role of striatal dopaminergic receptors in amphetamine-induced behavioral facilitation.
    J Pharmacol Exp Ther. 1982 Jun;221(3):650-5 PMID: 7201019
  25. Blockade of behavioral sensitization to cocaine and amphetamine by inhibitors of protein synthesis.
    Brain Res. 1993 Feb 12;603(1):19-24 PMID: 8453474
  26. Ethanol, like psychostimulants and morphine, causes long-lasting hyperreactivity of dopamine and acetylcholine neurons of rat nucleus accumbens: possible role in behavioural sensitization.
    Psychopharmacology (Berl). 1997 Sep;133(1):69-76 PMID: 9335083
  27. Stimulation of [3H]dopamine release by nicotine in rat nucleus accumbens.
    J Neurochem. 1987 Nov;49(5):1449-54 PMID: 2889800
  28. Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8716-20 PMID: 8710937
  29. Stressor- or drug-induced sensitization of the corticosterone response is not critically involved in the long-term expression of behavioural sensitization to amphetamine.
    Neuroscience. 1999;92(1):343-52 PMID: 10392855
  30. Suppressive effect of cycloheximide on behavioral sensitization to methamphetamine in mice.
    Eur J Pharmacol. 1993 Mar 30;234(1):67-75 PMID: 8472762
  31. Intermittent morphine administration induces a long-lasting synergistic effect of corticosterone on dopamine D1 receptor functioning in rat striatal GABA neurons.
    Synapse. 1997 Apr;25(4):381-8 PMID: 9097397
  32. Muscarinic modulation of striatal dopamine, glutamate, and GABA release, as measured with in vivo microdialysis.
    J Neurochem. 1997 May;68(5):1942-8 PMID: 9109520
  33. Amphetamine administered to the ventral tegmental area sensitizes rats to the locomotor effects of nucleus accumbens amphetamine.
    J Pharmacol Exp Ther. 1994 Aug;270(2):690-6 PMID: 8071860
  34. Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum.
    Brain Res. 1975 Sep 5;94(3):507-22 PMID: 1171714
  35. Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat.
    J Neurosci. 1990 Jan;10(1):303-10 PMID: 2299396
  36. Locomotor-activating effects of the D2 agonist bromocriptine show environment-specific sensitization following repeated injections.
    Psychopharmacology (Berl). 1992;107(2-3):277-84 PMID: 1535445
  37. Tolerance and sensitization to the behavioral effects of drugs.
    Behav Pharmacol. 1993;4(4):289-312 PMID: 11224198
  38. Persistent sensitization of dopamine neurotransmission in ventral striatum (nucleus accumbens) produced by prior experience with (+)-amphetamine: a microdialysis study in freely moving rats.
    Brain Res. 1988 Oct 18;462(2):211-22 PMID: 2847849
  39. Inhibition of d-amphetamine-induced locomotor activity by injection of haloperidol into the nucleus accumbens of the rat.
    Psychopharmacologia. 1975;41(2):87-95 PMID: 1098086
  40. A direct comparison of amphetamine-induced behaviours and regional brain dopamine release in the rat using intracerebral dialysis.
    Brain Res. 1987 Jan 20;401(2):322-30 PMID: 3815099
  41. Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions.
    Trends Neurosci. 1994 Jun;17(6):228-33 PMID: 7521083
  42. Lack of cross-sensitization of the locomotor effects of morphine in amphetamine-treated rats.
    Neuropsychopharmacology. 1999 Oct;21(4):550-9 PMID: 10481839
  43. Possible involvement of medial prefrontal cortex in amphetamine-induced sensitization of mesolimbic dopamine function.
    Eur J Pharmacol. 1995 Aug 25;282(1-3):157-67 PMID: 7498271
  44. Amphetamine injection into the ventral mesencephalon sensitizes rats to peripheral amphetamine and cocaine.
    J Pharmacol Exp Ther. 1988 Jun;245(3):1095-102 PMID: 3385638
  45. Dopaminergic mechanisms mediating the long-term expression of locomotor sensitization following pre-exposure to morphine or amphetamine.
    Psychopharmacology (Berl). 1999 Apr;143(3):244-53 PMID: 10353426
  46. Evidence of a complete independence of the neurobiological substrates for the induction and expression of behavioral sensitization to amphetamine.
    Neuroscience. 1995 Mar;65(2):385-95 PMID: 7777156
  47. Sensitization to the psychomotor stimulant effects of amphetamine: modulation by associative learning.
    Behav Neurosci. 1996 Dec;110(6):1397-414 PMID: 8986341
  48. Intermittent versus continuous stimulation: effect of time interval on the development of sensitization or tolerance.
    Life Sci. 1980 Apr 21;26(16):1275-82 PMID: 6991841
  49. Toward a molecular biology of memory: the light's coming on!
    Nat Neurosci. 1998 Nov;1(7):543-5 PMID: 10196558
  50. Expression of cocaine sensitization: regulation by the medial prefrontal cortex.
    Neuroscience. 1999;88(3):765-74 PMID: 10363816
  51. Application of a protein synthesis inhibitor into the ventral tegmental area, but not the nucleus accumbens, prevents behavioral sensitization to cocaine.
    Synapse. 1995 Jul;20(3):217-24 PMID: 7570353
  52. D-2 but not D-1 dopamine agonists produce augmented behavioral response in rats after subchronic treatment with methamphetamine or cocaine.
    Psychopharmacology (Berl). 1990;102(4):459-64 PMID: 2151400
  53. Corticosterone and dexamethasone act at different brain sites to inhibit adrenalectomy-induced adrenocorticotropin hypersecretion.
    Brain Res. 1988 Dec 6;474(2):205-10 PMID: 2850089
  54. Morphine-induced long-term sensitization to the locomotor effects of morphine and amphetamine depends on the temporal pattern of the pretreatment regimen.
    Psychopharmacology (Berl). 1997 May;131(2):115-22 PMID: 9201798
  55. Mifepristone prevents the expression of long-term behavioural sensitization to amphetamine.
    Eur J Pharmacol. 1996 Jun 27;307(2):R3-4 PMID: 8832229
  56. Circulating adrenal hormones are not necessary for the development of sensitization to the psychomotor activating effects of amphetamine.
    Brain Res. 1995 Feb 27;673(1):13-24 PMID: 7757465
  57. Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization.
    Eur J Neurosci. 1998 Nov;10(11):3565-71 PMID: 9824469
  58. Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization.
    J Pharmacol Exp Ther. 1993 Jan;264(1):249-55 PMID: 8093727
  59. Effect of adrenalectomy on the initiation and expression of cocaine-induced sensitization.
    Psychopharmacology (Berl). 1996 Jun;125(3):265-73 PMID: 8815963
  60. Effect of repeated methamphetamine administrations on dopamine and glutamate efflux in rat prefrontal cortex.
    Brain Res. 1995 Nov 27;700(1-2):99-106 PMID: 8624733
  61. The neural basis of drug craving: an incentive-sensitization theory of addiction.
    Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91 PMID: 8401595
  62. Long-term facilitation of amphetamine-induced rotational behavior and striatal dopamine release produced by a single exposure to amphetamine: sex differences.
    Brain Res. 1982 Dec 16;253(1-2):231-41 PMID: 6891283
  63. The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants.
    Prog Neurobiol. 1998 Apr;54(6):679-720 PMID: 9560846
  64. One injection of cocaine produces a long-lasting increase in [3H]-dopamine release.
    Pharmacol Biochem Behav. 1987 Jul;27(3):533-5 PMID: 3659076
  65. Nicotine infused into the nucleus accumbens increases synaptic dopamine as measured by in vivo microdialysis.
    Brain Res. 1989 Jan 30;478(2):365-7 PMID: 2924134
  66. Physiological role of corticotropin-releasing factor in the control of adrenocorticotropin-mediated corticosterone release from the rat adrenal gland.
    Endocrinology. 1992 Jan;130(1):282-8 PMID: 1309333
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
1999-11-01
Pages
9579-86
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6782918
Subset
IM
External Links
PubMed source PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2