Endocrine effects of methadone in rats; acute effects in adults

The effects of methadone (METH) on serum levels of prolactin (PRL), growth hormone (GH), corticosterone (CS), TSH and T4 were determined in male and female rats. METH initially (15-45 min after injection) decreased TSH and increased PRL, GH and CS in both male and female rats. These changes were followed by a rebound decrease in CS and increase in TSH 4 h after METH administration. METH decreased GH at 0.1 mg/kg, but increased secretion with doses of 0.5 mg/kg and higher. Changes in PRL, CS and TSH were only seen with 1 mg/kg and higher. Naloxone blocked increases in serum GH, PRL and CS and the decrease in TSH caused by METH. Serum PRL increased significantly more in females than in males, although other endocrine actions of METH were the same in males and females. Pretreatment of animals with METH 4 h before a second challenge dose did not affect TSH, PRL or GH responses to METH. However, peak CS levels were lower in pretreated animals than in controls. These findings demonstrate that METH elicits a complex profile of endocrine response which probably reflects actions at multiple receptor and/or anatomical sites, and suggest that reported sex differences in METH metabolism are not limiting in determining the hormonal response to this drug. These results also suggest that single-dose tolerance develops to the effects of METH on CS but not on other endocrine parameters.