Endocrine, immune, and neurochemical changes in rats during withdrawal from chronic amphetamine intoxication.
In humans who chronically abuse amphetamine (AMPH), sudden abstinence often precipitates an organic mood disorder that mimics many symptoms of major depression. We report that AMPH exposure and withdrawal in rats modifies hypothalamic-pituitary-adrenal axis endocrine responses, peripheral immune functions, and regional brain catecholamine levels. Compared to vehicle-treated animals, rats treated with AMPH for 10 days exhibit significantly decreased physostigmine-induced release of adrenocorticotropin hormone (ACTH). During AMPH withdrawal, these animals show a loss of the normal correlation between levels of plasma ACTH and corticosterone. Chronic AMPH treatment in rats causes a significant increase in natural killer cell activity. Brain dopamine levels in these animals are decreased in the caudate nucleus but are increased in the nucleus accumbens. AMPH withdrawal in rats may be a useful model for studying the physiologic and neural substrates of human AMPH withdrawal states.
Swerdlow
N R
NR
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093.
Hauger
R
R
Irwin
M
M
Koob
G F
GF
Britton
K T
KT
Pulvirenti
L
L
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D015415:Biomarkers; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D003866:Depressive Disorder / Q000378:metabolism; D004702:Endocrine Glands / Q000502:physiology*; D007107:Immune System / Q000502:physiology*; D066298:In Vitro Techniques; D007694:Killer Cells, Natural / Q000187:drug effects; D008297:Male; D010830:Physostigmine / Q000494:pharmacology; D011388:Prolactin / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D015415:Biomarkers; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D003346:Corticotropin-Releasing Hormone; D010830:Physostigmine; D000661:Amphetamine