Effect of perinatal exposure to methadone on brain opioid and alpha 2-adrenergic receptors

Prenatal exposure to psychotropic drugs has recently been shown to induce behavioral and brain neurochemical changes in the newborn. The long-term effects of pre- and postnatal exposure to methadone on the opioid (delta and mu) and adrenergic (alpha 2) receptors were investigated in two areas of the rat brain. Rat pups received prenatal treatment with methadone through a minipump implanted in the pregnant dams and were cross-fostered to methadone- or non-methadone-implanted dams until weaned. The rats were sacrificed when fully grown and brains removed. Receptor binding assays using 3H-D-ala-leu-enkephalin and 3H-naloxone for delta and mu opioid receptors respectively and 3H-rauwolscine for alpha 2-adrenergic receptors were performed in two areas of the brain. In the hypothalamus, prenatal methadone treatment induced sustained decreases in both delta and mu opioid receptors but did not cause significant changes in the alpha 2-adrenergic receptors. In the cerebral cortex, prenatal methadone treatment induced significant decreases not only in delta and mu opioid receptors but also in alpha 2-adrenergic receptors. Postnatal methadone treatment alone did not cause significant changes in opioid receptors in the two brain areas, but did induce reduction in the cerebral cortical alpha 2-adrenergic receptors. The significance of these results is discussed.