Alcohol-Conditioned Place Preference in Male and Female Rats Exposed to Perigestational Morphine

Since 2004, cases of neonatal opioid withdrawal syndrome (NOWS) have increased by almost 500%. Despite this, the long-term outcomes associated with NOWS are largely unknown. While limited research has suggested that prenatal exposure to morphine in rats has a direct impact on future recreational drug use, these studies lack a translational model. Our lab has recently developed a model of perigestational opioid use that recapitulates clinical drug use by women of reproductive age. Our goal is to use this model to explore changes in alcohol-directed behavior as a result of early life morphine exposure. Alcohol was chosen as it is the most common drug in the US and the first drug used by most individuals. Our model of perigestational opioid exposure (POE) involves implantation of subcutaneous osmotic pumps into adult female rats. These pumps administer 10-16 mg/kg of morphine daily beginning prior to breeding and continuing through the first postpartum week. As juveniles, rats (POE or saline) are tested using a conditioned place preference paradigm (CPP). For this assay, rats are placed in a 2-chamber apparatus; one chamber is paired with alcohol and another with saline. On the test day, the room in which the rat spends the most amount of time is considered its preferred room (i.e., CPP). Prior to this, rats are introduced to alcohol in the form of 10% ethanol in gelatin for 16 days to acclimate them to alcohol reward. No differences in voluntary consumption of alcohol gelatin were observed for POE or saline groups, with both consuming levels representative of abusive consumption in humans. Next, to induce a CPP, morphine-exposed rats were given alternating alcohol and saline injections twice daily over four days in one of the two chambers. On the final day, rats were allowed to freely roam the two rooms to assess for preference (alcohol or saline paired). Our results indicated that POE rats spent more time in the alcohol-paired room, indicating that they had formed an alcohol-paired CPP. Overall, these studies contribute to growing evidence of the potentially long-term characteristics of NOWS.