Adrenocorticotropin Stress Response but Not Glucocorticoid-Negative Feedback Is Altered by Prenatal Morphine Exposure in Adult Male Rats

Abstract

The present study was designed to investigate the effects of prenatal morphine exposure on the hypothalamic-pituitary-adrenal (HPA) axis-regulated stress responses by measuring restraint stress-induced changes in the adrenocorticotropic hormone (ACTH) and corticosterone (CORT) levels. In experiment 1, plasma levels of ACTH and CORT in prenatally morphine-, saline-exposed and control male rats were determined before and at several times after restraint stress. There were no statistically significant differences in plasma ACTH and CORT levels before restraint stress between the groups. However, prenatal morphine exposure dampened the stress-induced increase and spontaneous recovery of ACTH levels after the restraint stress. There were no differences in plasma CORT levels between the three groups either before or at any time after restraint stress. Experiment 2 was designed to investigate the sensitivity of negative feedback of glucocorticoids using the dexamethasone (DEX) suppression test. DEX was administered at different doses (0.001, 0.01, 0.1 and 1.0 mg/kg) and ACTH and CORT plasma levels were measured before and at several times after restraint stress in prenatally morphine- and saline-exposed males. DEX pretreatment eliminated the differences observed in ACTH responses to stress in morphine- and saline-exposed males. DEX pretreatment dose dependently suppressed the restraint stress-induced increased plasma ACTH concentration. In plasma CORT levels, DEX pretreatment dose dependently suppressed the restraint stress-induced increased plasma CORT concentration regardless of prenatal drug exposure. Thus, the present study demonstrates that prenatal morphine exposure alters the ACTH and CORT responses to stress but not the sensitivity of negative feedback of glucocorticoids.

Behavioral effects of perinatal opioid exposure

“…Therefore, it is important to note that prenatal opiate exposure followed by postnatal withdrawal diminished the stress axis response to immunological and social stressors in neonatal rats, whereas in adulthood, an exaggerated response was detected (Hamilton et al, 2005). The adrenocorticotropin (ACTH, the hypophyseal component of the stress response) and corticosterone (a rodent glucocorticoid in the adrenal cortex) responses are dissociated (Rimanoczy et al, 2003;Slamberova et al, 2004). Although there were no differences in basal levels between control animals and intra-and postnatal morphine-treated animals, stressor-induced ACTH elevations were smaller in the opioid-exposed groups.…”

Morphine Versus Clonidine for Neonatal Abstinence Syndrome

“…Antenatal opiate exposure affects brain development 9,10 with resulting decreases in corticogenesis, neurogenesis, and synaptogenesis 11,12 and alterations in the ontogeny of the stress axis [13][14][15] and immune response. 16 Human studies also allude to the association of prenatal opiate exposure and small head circumference [17][18][19][20] and decreased brain volumes found on imaging.…”

Hypothalamo-Pituitary-Adrenal Axis-Regulated Stress Response and Negative Feedback Sensitivity Is Altered by Prenatal Morphine Exposure in Adult Female Rats

“…Recently, we [2]demonstrated that prenatal morphine exposure diminishes the stress-induced increase in adrenocorticotropic hormone (ACTH) plasma concentration and delays the return of ACTH to basal level in male rats. Basal levels of ACTH, however, did not differ between morphine- and saline-exposed males [2]. In addition, there was no effect of prenatal morphine exposure on basal or stress-induced corticosterone (CORT) levels [2].…”