Role of noradrenergic hyperactivity in neonatal opiate abstinence.
Despite the existence of a well-defined abstinence syndrome in offspring of opiate-dependent mothers, the mechanisms involved in neonatal abstinence remain unclear. The goal of the present study was to determine the contribution of noradrenergic neurons in the opiate abstinence syndrome in neonatal rats (10 days old). First, the ability of the alpha 2-adrenergic agonist, clonidine to attenuate the symptoms of neonatal opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring postmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypothalamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opiate abstinence was characterized by an increased incidence of wall climbing, tremors and mouthing. Acute treatment with morphine and naloxone in chronic saline-treated pups also produced the tremor, albeit less severe than in pups treated chronically with morphine. Clonidine (0.2 mg/kg) attenuated the expression of tremor and mouthing in neonates, but increased wall climbing. Clonidine elicited wall climbing in opiate-naive neonates. Treatment with morphine followed by naltrexone increased MHPG levels in all of the brain areas examined, irrespective of the chronic treatment, but naltrexone treatment elicited a larger increase in MHPG levels in pups treated chronically with morphine. Acute morphine treatment increased MHPG levels only in the hypothalamus. The results of the present study provide behavioral and neurochemical data supporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.
Little
P J
PJ
Department of Pharmacology, Duke University Medical Center, Durham, NC 27710, USA.
Price
R R
RR
Hinton
R K
RK
Kuhn
C M
CM
D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003000:Clonidine / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists / Q000627:therapeutic use; D009294:Narcotics / Q000009:adverse effects*; D009357:Neonatal Abstinence Syndrome / Q000473:pathology / Q000503:physiopathology* / Q000534:rehabilitation; D009460:Neurologic Examination / Q000187:drug effects; D009638:Norepinephrine / Q000502:physiology*; D009293:Opioid-Related Disorders / Q000473:pathology / Q000503:physiopathology* / Q000534:rehabilitation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D008734:Methoxyhydroxyphenylglycol; D003000:Clonidine; D009638:Norepinephrine