Effect of Chronic Methadone Administration on Neuroendocrine Function in Developing Rats

Abstract

This paper reports the effects of chronic postnatal methadone administration on basal hormone levels and on the endocrine response to methadone. Chronic postnatal methadone administration delayed normal developmental increases in serum T(4) (decrease on day 5), corticosterone (CS) (days 15 and 20) and growth hormone (GH) (day 25). In addition, marked tolerance to methadone effects on GH, CS, thyroid-stimulating hormone (TSH) and prolactin (PRL) secretion developed during chronic postnatal administration, and effects on PRL and TSH secretion persisted after drug withdrawal.

Opiate withdrawal in the neonatal rat: relationship to duration of treatment and naloxone dose

“…Previous studies have shown that shipping the dams from this local supplier does not affect the development of opiate tolerance or dependence in the pup (Kuhn and Bartolome 1984). They were housed in the testing rooms to prevent stress-induced changes in hormone and behavioral responses associated with removal from a familiar environment (Brown and Martin 1974;Krulich et al 1974).…”

“…A significant percentage of infants born to opiateaddicted or methadone-maintained mothers are small for gestational age, and show a number of somatic and behavioral abnormalities McLaughlin 1977, 1978;Kuhn and Bartolome 1984). Infants exposed prenatally to opiates undergo a well-characterized opiate withdrawal (Dattel 1990;Hutchings and Dow-Edwards 1991).…”

“…Therefore, we also used an endocrine index of withdrawal because these measures do not change qualitatively over time. ACTH and corticosterone secretion (Kuhn and Bartolome 1985;Kuhn and Windh 1991) are commonly used endocrine markers for withdrawal in adults. However, these hormonal indices are less useful in neonates because they remain elevated for several hours after each MOR dose .…”

“…Therefore, the endocrine response to MOR cannot be distinguished from precipitated withdrawal unless long post-morphine treatment times are used. MOR-induced changes in GH secretion are quite brief, and so provide a more useful endocrine index of withdrawal in rats (Kuhn and Schanberg 1981;Kuhn and Bartolome 1985).…”

Morphine Withdrawal Alters Anterior Pituitary Hormone Secretion, Brain Endopeptidase Activity and Brain Monoamine Metabolism in the Rat

“…Physical dependence also ensues resulting in pronounced withdrawal symptoms on cessation of the opioid administration. In addition to the typical behavioural symptoms, opioid withdrawal has been associated with profound changes in anterior pituitary hormone secretion (Gabriel r t d. 1985: Kuhn & Bartolome 1985Rauhala el (r/. 1988).…”