Chronic Cocaine Exposure During Pregnancy Increases Postpartum Neuroendocrine Stress Responses

Abstract

The cycle of chronic cocaine (CC) use and withdrawal results in increased anxiety, depression and disrupted stress-responsiveness. Oxytocin and corticosterone (CORT) interact to mediate hormonal stress responses and can be altered by cocaine use. These neuroendocrine signals play important regulatory roles in a variety of social behaviours, specifically during the postpartum period, and are sensitive to disruption by CC exposure in both clinical settings and preclinical models. To determine whether CC exposure during pregnancy affected behavioural and hormonal stress response in the early postpartum period in a rodent model, Sprague-Dawley rats were administered cocaine daily (30 mg/kg) throughout gestation (days 1–20). Open field test (OFT) and forced swim test (FST) behaviours were measured on postpartum day 5. Plasma CORT concentrations were measured prior to and following testing throughout the test day, while plasma and brain oxytocin concentrations were measured post-testing only. Results indicated increased CORT response following the OFT in CC-treated dams (p≤ 0.05). CC-treated dams also exhibited altered FST behaviour (p≤ 0.05), suggesting abnormal stress responsiveness. Peripheral, but not central, oxytocin levels were increased by cocaine treatment (p≤ 0.05). Peripheral oxytocin and CORT increased following the FST regardless of treatment condition (p≤ 0.05). Changes in stress-responsiveness, both behaviourally and hormonally may underlie some deficits in maternal behaviour, thus a clearer understanding of CC’s effect on the stress response system may potentially lead to treatment interventions which could be relevant to clinical populations. Additionally, these results indicate that CC treatment can have long-lasting effects on peripheral oxytocin regulation in rats, similar to changes observed in persistent social behaviour and stress-response deficits in clinical populations.

Chronic Methamphetamine Self‐Administration Dysregulates Oxytocin Plasma Levels and Oxytocin Receptor Fibre Density in the Nucleus Accumbens Core and Subthalamic Nucleus of the Rat

“…Plasma oxytocin levels have previously been examined after acute MDMA or chronic MDMA, METH and cocaine exposure . The present study demonstrated that, compared to controls, IVSA METH significantly increased plasma oxytocin levels, which remained elevated after 15 days of extinction.…”

“…No changes in CRF-IR fibre staining or plasma CORT concentration were identified when comparing the rats that self-administered METH and the yoked saline rats. Plasma oxytocin levels have previously been examined after acute MDMA or chronic MDMA, METH and cocaine exposure (12,20,35,36). The present study demonstrated that, compared to controls, IVSA METH significantly increased plasma oxytocin levels, which remained elevated after 15 days of extinction.…”

“…Our baseline levels of oxytocin are similar to those measured previously with chronic IVSA METH sustaining a four‐fold increase in this level. The effect of acute METH administration on plasma oxytocin levels is yet to be reported; however, our data and those of other studies suggest that acute MDMA and chronic cocaine administration can increase plasma oxytocin levels. By contrast to these findings, Sarnyai et al .…”

Prenatal and gestational cocaine exposure: Effects on the oxytocin system and social behavior with implications for addiction

“…On PPD 5, following a pup retrieval task, CC-exposed mothers had reduced plasma Oxt compared to controls, with no differences in brain Oxt in the MPOA, VTA, HIPP or nucleus accumbens (Williams et al, 2011a). However, CC-exposed mothers have higher baseline plasma levels of Oxt, and enhanced plasma Oxt response to stress (the forced swim test), but no altered HIPP or AMY responses (Williams et al, 2012). This suggests that CC-induced changes in Oxt are sensitive to behavioral context.…”

“…Furthermore, addiction-related increases in anxiety and depression are thought to be partially mediated by overactive stress systems in the brain (Rotzinger et al, 2010; Logrip et al, 2011). The changes in brain and plasma Oxt following cocaine exposure suggest that other social behaviors, stress reactivity or responsiveness to drugs may be altered in chronically drug exposed females which may help explain relapse into addiction or increased postpartum mood disorders observed in these clinical populations (Williams et al, 2012; Rutherford et al, 2011). …”