ROLE OF NORADRENERGIC HYPERACTIVITY IN NEONATAL OPIATE ABSTINENCE

Despite the existence of a well-defined abstinence syndrome in offspri ng of opiate-dependent mothers, the mechanisms involved in neonatal ab stinence remain unclear. The goal of the present study was to determin e the contribution of noradrenergic neurons in the opiate abstinence s yndrome in neonatal rats (10 days old). First, the ability of the alph a 2-adrenergic agonist, clonidine to attenuate the symptoms of neonata l opiate abstinence precipitated by naloxone was determined. Secondly, the activity of noradrenergic neurons was determined by measuring pos tmortem levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) in the hypoth alamus, hippocampus and cortex in opiate-abstinent pups. Neonatal opia te abstinence was characterized by an increased incidence of wall clim bing, 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, b ut increased wall climbing. Clonidine elicited wall climbing in opiate -naive neonates. Treatment with morphine followed by naltrexone increa sed MHPG levels in all of the brain areas examined, irrespective of th e chronic treatment, but naltrexone treatment elicited a larger increa se in MHPG levels in pups treated chronically with morphine. Acute mor phine treatment increased MHPG levels only in the hypothalamus. The re sults of the present study provide behavioral and neurochemical data s upporting the hypothesis that noradrenergic hyperactivity plays a role in neonatal opiate abstinence.