Exposure to ethanol on prenatal days 19–20 increases ethanol intake and palatability in the infant rat: Involvement of kappa and mu opioid receptors

Abstract

Prenatal exposure to ethanol on gestation Days 19-20, but not 17-18, increases ethanol acceptance in infant rats. This effect seems to be a conditioned response acquired prenatally, mediated by the opioid system, which could be stimulated by ethanol's pharmacological properties (mu-opioid receptors) or by a component of the amniotic fluid from gestation-day 20 (kappa-inducing factor). The latter option was evaluated administering non-ethanol chemosensory stimuli on gestation Days 19-20 and testing postnatal intake and palatability. However, prenatal exposure to anise or vanilla increased neither intake nor palatability of these tastants on postnatal Day 14. In experiment 2, the role of ethanol's pharmacological effect was tested by administering ethanol and selective antagonists of mu and kappa opioid receptors prenatally. Blocking the mu-opioid receptor system completely reversed the effects on intake and palatability, while antagonizing kappa receptors only partially reduced the effects on palatability. This suggests that the pharmacological effect of ethanol on the fetal mu opioid system is the appetitive reinforcer, which induces the prenatally conditioned preference detected in the preweanling period.

Kappa opioid receptor signaling in the brain: Circuitry and implications for treatment

“…Interestingly, prenatal exposure to alcohol increases ethanol intake later, and this effect is partially blocked by KOR antagonists (Diaz-Cenzano et al 2014). And, despite the abundance of this behavioral evidence, little has been done to investigate the mechanism of interaction between alcohol and KORs, and most of the existing literature focuses in the central amygdala (Gilpin et al 2014, Kang-Park et al 2013, Kissler et al 2014).…”

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

“…These factors were carefully selected based on their known involvement in both ethanol intake and reinforcement throughout early development (e.g., [9], [14], [18], [19], [20], and [35]) and adulthood (e.g., [21], [22], [23], [24], [25], and [26]). Each factor was examined in three brain regions - the nucleus accumbens, ventral tegmental area, and hypothalamus - sites known to be both high in opioid-containing neurons and implicated in general consummatory behavior or ethanol's appetitive effects.…”

“…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.…”

“…Known to be involved in ethanol intake and reinforcement during adulthood, the endogenous opioid system has also been implicated in ethanol's appetitive effects during early postnatal life (e.g., [18], [9], [19], [20], and [14]). Administration of a mu or kappa opioid receptor antagonist, for example, was sufficient to eliminate ethanol reinforcement normally observed in the infant rat [19] and [20].…”

“…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.…”