Affective and neuroendocrine effects of withdrawal from chronic, long-acting opiate administration.
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.
Department of Psychology, University of Minnesota, 75 East River Road, Minneapolis, MN 55455, USA. Electronic address: hamiltonk@uwstout.edu.
Kathryn L
KL
Hamilton
Andrew C
AC
Harris
Jonathan C
JC
Gewirtz
D000339:Affect / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000097:blood; D008297:Male; D008692:Methadyl Acetate / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D009490:Neurosecretory Systems / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000503:physiopathology* / Q000523:psychology
D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D008692:Methadyl Acetate; D003345:Corticosterone
ANOVA; Acoustic startle; CRF1; CS; Corticosterone; Fear-potentiated startle; HPA; LAAM; NX; Opiate dependence; Opiate withdrawal; analysis of variance; conditioned stimulus; corticotrophin releasing factor-1; hypothalamic–pituitary–adrenal; l-alpha-acetylmethadol; naloxone