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PMID: 2062986 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Time course of transient behavioral depression and persistent behavioral sensitization in relation to regional brain monoamine concentrations during amphetamine withdrawal in rats.

Psychopharmacology ·Vol. 103 ·No. 4 ·1991-00-00 ·Pages 480-92

Paulson PE, Camp DM, Robinson TE

Abstract

This experiment was designed to characterize the withdrawal syndrome produced by discontiuation of treatment with escalating, non-neurotoxic doses of d-amphetamine (AMPH). AMPH withdrawal was associated with both transient and persistent changes in behavior and postmortem brain tissue catecholamine concentrations. During the first week of withdrawal rats showed a significant decrease in spontaneous nocturnal locomotor activity. This behavioral depression was most pronounced on the first 2 days after the discontinuation of AMPH pretreatment, was still evident after 1 week, but had dissipated by 4 weeks. Behavioral depression was not due to a simple motor deficit, because AMPH-pretreated animals showed a normal large increase in locomotion when the lights initially went out, but they did not sustain relatively high levels of locomotor activity throughout the night, or show the early morning rise in activity characteristic of controls. Behavioral depression was associated with the transient decrease in the concentration of norepinephrine (NE) in the hypothalamus, and a transient decrease in the ability of an AMPH challenge to alter dopamine (DA) concentrations in the caudate-putamen and nucleus accumbens. AMPH pretreatment also produced persistent changes in brain and behavior. The persistent effects of AMPH were not evident in spontaneous locomotor activity, but were revealed by a subsequent challenge injection of AMPH. AMPH pretreated animals were markedly hyper-responsive to the stereotypy-producing effects of an AMPH challenge. This behavioral sensitization was not fully developed until 2 weeks after the discontinuation of AMPH pretreatment, but then persisted undiminished for at least 1 year. It is suggested that the transient changes in brain and behavior described here may represent an animal analogue of the "distress syndrome" seen in humans during AMPH withdrawal, which is associated with symptoms of depression and alterations in catecholamine function. On the other hand, persistent behavioral sensitization may be analogous to the enduring hypersensitivity to the psychotogenic effects of AMPH seen in former AMPH addicts.

MeSH Terms
Amphetamine/pharmacology Animals Behavior, Animal/drug effects Biogenic Monoamines/metabolism Brain Chemistry/drug effects Depression, Chemical Dopamine/metabolism Female Norepinephrine/metabolism Rats Stereotyped Behavior/drug effects Substance Withdrawal Syndrome/metabolism Time Factors
Chemicals
Biogenic Monoamines Amphetamine Dopamine Norepinephrine
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Paulson P E
Department of Psychology, University of Michigan, Ann Arbor 48109.
Camp D M
Robinson T E
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Article Info
Journal
Psychopharmacology
Abbr.
Psychopharmacology (Berl)
ISSN
0033-3158
DOI
10.1007/BF02244248
Published
1991-00-00
Pages
480-92
Language
English
Region
Germany
NLM ID
7608025
PMCID
PMC1865099
Subset
IM
Grants
NIDA NIH HHS · R01 DA004294 · United States
PHS HHS · 04294 · United States
External Links
PubMed source DOI: 10.1007/BF02244248 PMC Full Text View journal details
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