Prenatal exposure to ethanol during late gestation facilitates operant self-administration of the drug in 5-day-old rats

Abstract

Prenatal ethanol exposure modifies postnatal affinity to the drug, increasing the probability of ethanol use and abuse. The present study tested developing rats (5-day-old) in a novel operant technique to assess the degree of ethanol self-administration as a result of prenatal exposure to low ethanol doses during late gestation. On a single occasion during each of gestational days 17–20, pregnant rats were intragastrically administered ethanol 1 g/kg, or water (vehicle). On postnatal day 5, pups were tested on a novel operant conditioning procedure in which they learned to touch a sensor to obtain 0.1% saccharin, 3% ethanol, or 5% ethanol. Immediately after a 15-min training session, a 6-min extinction session was given in which operant behavior had no consequence. Pups were positioned on a smooth surface and had access to a touch-sensitive sensor. Physical contact with the sensor activated an infusion pump, which served to deliver an intraoral solution as reinforcement (Paired group). A Yoked control animal evaluated at the same time received the reinforcer when its corresponding Paired pup touched the sensor. Operant behavior to gain access to 3% ethanol was facilitated by prenatal exposure to ethanol during late gestation. In contrast, operant learning reflecting ethanol reinforcement did not occur in control animals prenatally exposed to water only. Similarly, saccharin reinforcement was not affected by prenatal ethanol exposure. These results suggest that in 5-day-old rats, prenatal exposure to a low ethanol dose facilitates operant learning reinforced by intraoral administration of a low-concentration ethanol solution. This emphasizes the importance of intrauterine experiences with ethanol in later susceptibility to drug reinforcement. The present operant conditioning technique represents an alternative tool to assess self-administration and seeking behavior during early stages of development.

Exploring associations between prenatal solvent exposures and teenage drug and alcohol use: a retrospective cohort study

“…In particular, increases in risk of alcohol disorders later in life have been observed, independent of other intervening factors such as maternal smoking and drinking during childhood [14, 15]. Animal and human data support the hypothesis that prenatal alcohol exposure increases affinity for later use [16], and alcohol exposure during pregnancy is known to have adverse effects on brain development [17]. In particular, fetal alcohol spectrum disorders (FASD), a condition resulting from high levels of maternal alcohol consumption, ranges from severe effects such as facial anomalies and growth retardation to mild and moderate effects on cognition and behavior, including impacts on executive functioning and motor control [18].…”

Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period

“…Consumption of smaller amounts of ethanol during this critical period of development, however, may result in less obvious, yet equally devastating consequences. Recent research suggests that even moderate exposure to ethanol during the last portion of gestation or early postnatal life may enhance ethanol intake [5], [6], [7], [8], [9], [10], and [11], preference [6], [12], and [13], and reinforcement [14], [15], [16], and [17] throughout life. The neurochemical and neuroanatomical mechanisms mediating these effects, however, are currently unknown.…”

“…Brain tissue was collected across several days during early postnatal life (PDs 4, 8 and 12), focusing on ages at which ethanol intake is known to be relatively low, moderate, and high, respectively [30] and [31]. To the extent that ethanol intake is mediated by the endogenous opioid system (e.g., [32], but see [33]) and differs across early ontogeny, and prenatal exposure to the drug alters subsequent consumption (e.g., [5], [6], [7], [8], [9], [10], [11], and [34] and reinforcement [14], [15], [16], and [17] of the drug, we expected to see differences in basal levels of opioid mRNA and/or protein as a function of both ontogeny and prenatal alcohol exposure (PAE). More specifically, we expected to see ontogenetic-dependent upregulation of opioid systems, indicative of ongoing developmental changes within this system.…”

Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors

“…Extensive basic research in animal models demonstrates that prenatal or early neonatal alcohol exposure alters a variety of later behavioral (Abate, et al, 2008; Becker et al, 1993; 1993; Chotro & Arias, 2006; Middleton et al, 2009; March et al, 2009), consummatory (Chotro et al, 2007; Diáz-Cenzano et al, 2014; Miranda-Morales et al, 2014; Shea et al, 2012; Youngentob & Glendinning. 2009), pharmacological (Diáz-Cenzano et al, 2014; Pautassi et al, 2012), biochemical (Middleton et al, 2009), and physiological (Eade et al, 2010; Taylor et al, 1981; Weinberg et al, 1995) responses to alcohol.…”